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Sun Q, Zhang K, Yang D, Liu Y, Xu Y, Zheng S. Proximal fibular osteotomy definitively ameliorates medial compartment knee osteoarthritis: A finite element analysis. J Orthop 2025; 69:47-52. [PMID: 40162047 PMCID: PMC11952842 DOI: 10.1016/j.jor.2025.03.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/10/2024] [Revised: 02/06/2025] [Accepted: 03/09/2025] [Indexed: 04/02/2025] Open
Abstract
Objective This study was designed to explore the biomechanical impacts of the proximal fibular osteotomy (PFO) on medial compartment knee osteoarthritis (KOA). Furthermore, this study utilized finite element analysis (FEA) to examine the biomechanical impacts of PFO on medial compartment KOA both pre- and post-surgery. Methods Fifteen individuals with medial compartment KOA were selected randomly. Three-dimensional reconstruction software, coupled with FEA software, was employed to model PFO, allowing observation of changes in stress distribution, peak stress, and contact area of articular cartilage in femoral cartilage, tibial plateau cartilage, and meniscus before and after PFO. Results After PFO, significant changes in peak stress and stress distribution in the knee joint (KJ) were observed. The stress distribution shifts notably from the medial side to the lateral side. A significant reduction in peak values was observed in the medial femoral cartilage (changing from 1.91 ± 0.44 to 1.40 ± 0.14), medial meniscus (2.89 ± 0.72 to 2.05 ± 0.49), and medial tibial plateau cartilage (2.25 ± 0.65 to 1.60 ± 0.38). On the contrary, an increase in these metrics was recorded in the lateral femoral cartilage (changing from 1.10 ± 0.32 to 1.59 ± 0.30), lateral meniscus (1.82 ± 0.58 to 2.49 ± 0.60), and lateral tibial plateau cartilage (0.95 ± 0.21 to 1.40 ± 0.26). In addition, the stress distribution area of articular cartilage was reduced significantly in the medial dimension (346.25 ± 55.66 to 267.05 ± 51.05) and increased in the lateral dimension (219.35 ± 38.89 to 333.25 ± 29.90). Conclusion PFO demonstrates effectiveness in alleviating stress within the medial compartment of the KJ, presenting a straightforward and efficacious approach for managing medial compartment KOA.
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Affiliation(s)
- Quan Sun
- College of Orthopedics and Traumatology, Guizhou University of Traditional Chinese Medicine, Guiyang, 550001, China
| | - Kaiwei Zhang
- The First Affiliated Hospital, Guizhou University of Traditional Chinese Medicine, Guiyang, 550001, China
| | - Di Yang
- The First Affiliated Hospital, Guizhou University of Traditional Chinese Medicine, Guiyang, 550001, China
| | - Yang Liu
- The First Affiliated Hospital, Guizhou University of Traditional Chinese Medicine, Guiyang, 550001, China
| | - Yuankun Xu
- The First Affiliated Hospital, Guizhou University of Traditional Chinese Medicine, Guiyang, 550001, China
| | - Shuguang Zheng
- The First Affiliated Hospital, Guizhou University of Traditional Chinese Medicine, Guiyang, 550001, China
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Fernandez C, Knoer G, Diaz P, Eom R, Gulati J, Bellaire CP, Argintar E. A retrospective comparison of Coronal Plane Alignment of the Knee. J Orthop 2025; 64:47-50. [PMID: 39691637 PMCID: PMC11647164 DOI: 10.1016/j.jor.2024.11.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/25/2024] [Accepted: 11/09/2024] [Indexed: 12/19/2024] Open
Abstract
Background Unicompartmental arthritic degeneration is treated by unicompartmental knee arthroplasties (UKA). The two current standards are mechanical alignment, where knee placement is perpendicular to the leg's mechanical axis and kinematic alignment, that consists of aligning the knee with the angles specific to the patient's innate bone structure. The purpose of this study was to compare knee alignment between mechanical and kinematic UKA. Methods A retrospective study at Medstar Washington Hospital Center from 2015 to 2022 identified 156 cases of knee arthroplasties. Of these, 95 had mechanical alignments and 61 had kinematic alignments. Patients were evaluated post-surgically for Coronal Plane Alignment of the Knee (CPAK). Analysis of post-operative joint x-ray imaging was performed, and the mechanical medial proximal tibial angle (MPTA) and lateral distal femoral angle (LDFA) were measured. The arithmetic hip knee ankle angle (aHKA) and joint line obliquity (JLO) were calculated. Results The CPAK results for mechanically aligned group demonstrated an average MPTA of 87.12 (±3), LDFA average of 86.04 (±3), aHKA average of 0.62 (±4) and JLO average of 172.57 (±4). The CPAK results for the kinematically aligned group demonstrated an average MPTA of 86.96 (±3), LDFA average of 84.67 (±3), aHKA average of 2.09 (±4), and JLO average of 171.1 (±4). A two-sample t-test on this data demonstrates statistically significant p-values of 0.004 for LDFA, 0.03 for aHKA, and 0.02 for JLO all below the 0.05 significance level. Both cohorts only contained CPAKs alignment types I and III. Conclusion This study demonstrated that there is a statistically significant difference in knee alignment when comparing mechanically versus kinematically aligned knees which suggests that there is an advantage for patients that undergo kinematically aligned knee replacements.
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Affiliation(s)
- Callie Fernandez
- Georgetown University School of Medicine, 3900 Reservoir Rd NW, Washington DC, 20007, USA
| | - Grace Knoer
- Georgetown University School of Medicine, 3900 Reservoir Rd NW, Washington DC, 20007, USA
| | - Perry Diaz
- Georgetown University School of Medicine, 3900 Reservoir Rd NW, Washington DC, 20007, USA
| | - Rachel Eom
- Georgetown University School of Medicine, 3900 Reservoir Rd NW, Washington DC, 20007, USA
| | - Jasmine Gulati
- Georgetown University School of Medicine, 3900 Reservoir Rd NW, Washington DC, 20007, USA
| | | | - Evan Argintar
- Georgetown University School of Medicine, 3900 Reservoir Rd NW, Washington DC, 20007, USA
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Liu Y, Wang Y, Cheng S, Mu J, Yin G, Gao H. Pantothenic acid alleviates osteoarthritis progression by inhibiting inflammatory response and ferroptosis through the SIRT1/Nrf2 signaling pathway. Chem Biol Interact 2025; 413:111494. [PMID: 40157627 DOI: 10.1016/j.cbi.2025.111494] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2025] [Revised: 03/03/2025] [Accepted: 03/26/2025] [Indexed: 04/01/2025]
Abstract
Osteoarthritis (OA) is a degenerative joint disease that is a major cause of deformity, swelling, pain and even loss of function in the knee joints of the elderly. Pantothenic acid (PA) plays a protective role in many organs due to its antioxidant and anti-inflammatory properties. Herein, we aimed to assess the protective role of PA on osteoarthritis and investigate the underlying molecular mechanism. The levels of inflammatory factors (IL-1β and TNF-α) in knee tissues were measured by ELISA. The Safranin O-Fast Green staining was used to assess the severity of OA and the H&E staining was used to assess the degree of synovitis. In vitro, the levels of iron, MDA, GSH were measured by the detection kits. Western blotting was used to assess the levels of signaling-related proteins. Our results showed that PA significantly attenuated the degree of cartilage degeneration in the MIA-induced osteoarthritis model. PA also reduced the expression of IL-1β, TNF-α, MMP1 and MMP3. In vitro, PA effectively reduced the concentrations of MMP1 and MMP3 in IL-1β-stimulated chondrocytes. PA decreased the levels of Fe2+ and MDA, while increasing GSH production and GPX4 and SLC7A11 expression in IL-1β-induced chondrocytes. Meanwhile, we found that PA was able to inhibit the phosphorylation level of p65, IκB protein in chondrocytes, which effectively blocked the NF-κB signaling pathway. Furthermore, PA also increased the level of SIRT1, Nrf2, and HO-1 protein expression. In addition, the inhibition of PA on IL-1β-induced MMPs production and ferroptosis were inhibited by the SIRT1 inhibitor EX-527. In conclusion, PA inhibited chondrocyte ferroptosis and cartilage destruction in osteoarthritis. The mechanism was through activating SIRT1/Nrf2 signaling pathway.
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Affiliation(s)
- Yi Liu
- Department of Bone and Joint Surgery, Orthopaedic Surgery Center, The First Hospital of Jilin University, Changchun, 130021, China
| | - Yang Wang
- The First Operation Room, The First Hospital of Jilin University, Changchun, 130021, China
| | - Shengqi Cheng
- Department of Bone and Joint Surgery, Orthopaedic Surgery Center, The First Hospital of Jilin University, Changchun, 130021, China
| | - Jie Mu
- Department of Bone and Joint Surgery, Orthopaedic Surgery Center, The First Hospital of Jilin University, Changchun, 130021, China
| | - Guanchen Yin
- Department of Bone and Joint Surgery, Orthopaedic Surgery Center, The First Hospital of Jilin University, Changchun, 130021, China
| | - Hang Gao
- Department of Bone and Joint Surgery, Orthopaedic Surgery Center, The First Hospital of Jilin University, Changchun, 130021, China.
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Zhou Y, Yu S, Xue B, Zhang X, Gao M, Liu Y. Analysis and ceRNA Network Construction of Differentially Expressed lncRNAs and mRNAs in Human Osteoarthritis Cartilage. Biochem Genet 2025:10.1007/s10528-025-11131-1. [PMID: 40358893 DOI: 10.1007/s10528-025-11131-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2024] [Accepted: 05/06/2025] [Indexed: 05/15/2025]
Abstract
This study aimed to identify differentially expressed long non-coding RNAs (lncRNAs) and messenger RNAs (mRNAs) in damaged cartilage (DC) and un-damaged cartilage (UDC) in human osteoarthritis (OA), exploring their roles in disease progression through bioinformatics analysis and ceRNA network construction. Cartilage samples from 5 OA patients undergoing total knee arthroplasty were analyzed. RNA sequencing was used to detect the expression of lncRNAs and mRNAs in DC and UDC samples. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to investigate biological processes. A ceRNA network was constructed, and differentially expressed RNAs were validated by quantitative real-time polymerase chain reaction (qRT-PCR). In the damaged cartilage (DC) samples, 5 lncRNAs were significantly upregulated, and 15 were significantly downregulated, while 8 mRNAs were upregulated, and 8 were downregulated. The differential expression of lncRNAs, including LINC01411, AL596087.2, PCDH20, LRFN2, and AL583785.1, was confirmed using qRT-PCR, with p-values for all results showing statistical significance (p < 0.05). GO/KEGG enrichment analysis revealed key pathways such as Ras, PI3K-Akt, and MAPK that were significantly involved in OA pathogenesis. The ceRNA network construction highlighted crucial miRNA interactions, identifying potential regulators of cartilage-related biological processes. Differentially expressed lncRNAs and mRNAs are involved in critical signaling pathways in OA cartilage, suggesting their potential as biomarkers or therapeutic targets for OA treatment. Further functional studies are needed to fully elucidate their roles in OA pathogenesis.
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Affiliation(s)
- Yong Zhou
- The Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
| | - Shengyuan Yu
- The Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China
| | - Bing Xue
- The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China
| | - Xi Zhang
- The Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China
| | - Ming Gao
- The Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China
| | - Yishu Liu
- The Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China
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Petrigna L, Amato A, Sortino M, Zanghì M, Musumeci G. Exploratory study on the feasibility of knee thermography evaluation in different body fat percentage. Res Sports Med 2025:1-14. [PMID: 40355320 DOI: 10.1080/15438627.2025.2505017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2024] [Accepted: 05/06/2025] [Indexed: 05/14/2025]
Abstract
Infrared thermography is increasingly adopted for pre-diagnosis and monitoring of different conditions. Knee osteoarthritis is widely studied and this pathology is often associated with obesity. Body fat is a confounding factor in the thermal imagine evaluation. Consequently, this study correlated the body fat percentage evaluated with the bioelectrical impedance analysis and thermal imagine of the knee region. Healthy young adults were recruited. The skin knee temperature and the bioelectrical impedance analysis were collected. A linear regression analysis was performed between the basal skin temperature of the knee region and weight, total fat percentage, right-leg and left-leg fat percentage. No associations were detected with weight, total fat percentage, and legs fat percentage. In the knee, in which the fat percentage is generally low, the fat percentage could be secondary in influencing the evaluation. This seems to make obesity not a limit during the skin thermal evaluation of the knee region.
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Affiliation(s)
- Luca Petrigna
- Department of Biomedical and Biotechnological Sciences, Section of Anatomy, Histology and Movement Science, School of Medicine, University of Catania, Catania, Italy
| | - Alessandra Amato
- Department of Biomedical and Biotechnological Sciences, Section of Anatomy, Histology and Movement Science, School of Medicine, University of Catania, Catania, Italy
| | - Martina Sortino
- Department of Biomedical and Biotechnological Sciences, Section of Anatomy, Histology and Movement Science, School of Medicine, University of Catania, Catania, Italy
| | - Marta Zanghì
- Department of Biomedical and Biotechnological Sciences, Section of Anatomy, Histology and Movement Science, School of Medicine, University of Catania, Catania, Italy
| | - Giuseppe Musumeci
- Department of Biomedical and Biotechnological Sciences, Section of Anatomy, Histology and Movement Science, School of Medicine, University of Catania, Catania, Italy
- Research Center on Motor Activities (CRAM), University of Catania, Catania, Italy
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Lee M, Jing C, Lee K. Physical therapy vs. glucocorticoid injection in patients with meniscal tears and knee osteoarthritis: a multi-center, randomized, controlled trial. BMC Med 2025; 23:277. [PMID: 40346599 PMCID: PMC12065295 DOI: 10.1186/s12916-025-04113-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2025] [Accepted: 04/29/2025] [Indexed: 05/11/2025] Open
Abstract
BACKGROUND Physical therapy is commonly recommended for treating meniscus tears and knee osteoarthritis (KOA). However, data from randomized trials that compare the effectiveness of this treatment with that of glucocorticoid injections are lacking. METHODS This randomized, single-blind, multicenter trial included 273 patients with KOA who were divided into either the physical therapy group (n = 133) or the glucocorticoid injection group (n = 140). The physical therapy included kinesiology tape, exercise protocols, and exercise training programs to increase core stability and periprosthetic muscle strength. The primary endpoint was the overall Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score at 1 year. Additionally, proprioception and safety were assessed. All analyses were performed with the use of the intention-to-treat approach. The data are reported as percentages (%) (n), and the threshold for statistical significance was p < 0.05. RESULTS There was no significant difference in the baseline characteristics between the two groups (p > 0.05). The average (± SD) WOMAC score at 1-year was 76.85 ± 2.50 in the physiotherapy group. And 99.55 ± 2.09 in the glucocorticoid injection group (mean difference = - 22.70; 95% confidence interval [95% CI] - 23.43 to - 21.96; p < 0.001). Compared with the glucocorticoid injection group, the physical therapy group exhibited superior performance in terms of proprioception, especially in the eyes-closed in situ stepping test (14.27 ± 0.75 versus 5.98 ± 0.74; mean difference = 8.29; 95% CI 8.09-8.50; p < 0.001). The incidence of serious adverse events at the 1-year follow-up was comparable between the two groups. Most of these events were determined to be complications arising from physical therapy and glucocorticoid injection. CONCLUSIONS The results revealed that pain, quality of life, and balance were greater in the physiotherapy group than in the glucocorticoid injection group within the 1-year study period. However, the long-term effects beyond this timeframe remain unknown, and future studies with extended follow-up times are needed to confirm the sustainability of these benefits. TRIAL REGISTRATION The protocol was approved by the local ethics committee of the ethical commission of the Hebei Sports Science Research Institute (SEC20200213019) and Ethics Committee of Sichuan Taikang Hospital (SCTK-IRB-032). The study was registered at the Chinese Clinical Trial Registry (ChiCTR2000032508).
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Affiliation(s)
- Mingzhu Lee
- Sichuan Taikang Hospital, No. 881 Xianghe 1 Street, Huayang Community, Tianfu New Area, Chengdu, Sichuan, People's Republic of China
| | - Chao Jing
- The Sports Science Research Institute of Hebei Province, Shijiazhuang, China
| | - Kainan Lee
- Sichuan Taikang Hospital, No. 881 Xianghe 1 Street, Huayang Community, Tianfu New Area, Chengdu, Sichuan, People's Republic of China.
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7
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Zhou X, Yu Y, Guo J, Cao L, Zhang X, Deng Z. The effects of various physical modalities on pain in patients with knee osteoarthritis: A network meta-analysis. J Orthop 2025; 63:171-180. [PMID: 40271511 PMCID: PMC12013403 DOI: 10.1016/j.jor.2025.03.045] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/16/2024] [Revised: 03/14/2025] [Accepted: 03/23/2025] [Indexed: 04/25/2025] Open
Abstract
Objective This study aims to evaluate the effectiveness of various physical therapy methods in reducing pain for patients with knee osteoarthritis (KOA) through a network meta-analysis. Methods We conducted a comprehensive search across multiple databases, including PubMed, Embase, Cochrane Library, VIP, WanFang Data, and CNKI, to identify randomized controlled trials (RCTs) on physical therapies for KOA. The search spanned from the inception of each database to October 2024. The methodological quality of the studies was assessed using the Cochrane Handbook. Pain was measured using tools such as the visual analog scale, numeric pain rating scale, and the Western Ontario and McMaster University Osteoarthritis Index. All pain scores were standardized to a 10-point scale. Data collection and analysis were performed independently by two researchers using Stata 15.0 software. Results The analysis included 64 studies with 3855 patients and 12 physical therapy modalities. Based on the surface under the cumulative ranking curve (SUCRA), the most effective treatments were HILT, ESWT, Hydrotherapy, Land-EX, LLLT, Braces, tDCS, US, IFCs, SWD, Insoles, and TENS. Conclusion HILT appears to be the most effective treatment for pain relief in KOA patients. Further large-scale RCTs are needed to confirm these findings.
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Affiliation(s)
- Xin Zhou
- Department of Orthopedic Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, PR China
- Department of Orthopedic Surgery, Chongqing University Jiangjin Hospital, Centre Hospital of Jiangjin District, Chongqing, 402260, PR China
| | - Yating Yu
- Department of Orthopedic Surgery, Chongqing University Jiangjin Hospital, Centre Hospital of Jiangjin District, Chongqing, 402260, PR China
| | - Jinwei Guo
- Department of Orthopedic Surgery, Chongqing University Jiangjin Hospital, Centre Hospital of Jiangjin District, Chongqing, 402260, PR China
| | - Liezhen Cao
- Department of Orthopedic Surgery, Chongqing University Jiangjin Hospital, Centre Hospital of Jiangjin District, Chongqing, 402260, PR China
| | - Xiaohua Zhang
- Department of Orthopedic Surgery, Chongqing University Jiangjin Hospital, Centre Hospital of Jiangjin District, Chongqing, 402260, PR China
| | - Zhongliang Deng
- Department of Orthopedic Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, PR China
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Song C, Shen B, Chen C, Yang L, Zhang C, Liu F, Chen F, Wu X. Identification of ferroptosis-related genes and potential drugs in osteoarthritis. Inflamm Res 2025; 74:70. [PMID: 40299032 DOI: 10.1007/s00011-025-02040-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2025] [Revised: 04/08/2025] [Accepted: 04/14/2025] [Indexed: 04/30/2025] Open
Abstract
BACKGROUND Osteoarthritis (OA) is a common chronic degenerative joint disease in orthopedics, and ferroptosis is a newly identified mode of cell death present in OA. Inhibition of inflammatory cytokine expression and modulation of chondrocyte ferroptosis related pathways may be novel strategies for the treatment of OA. The purpose of this work was to uncover prospective biomarkers and molecular processes of ferroptosis in OA, as well as to better understand the molecular mechanisms of ferroptosis in OA treated with resveratrol. MATERIAL AND METHODS We obtained OA gene expression profiles from the Gene Expression Omnibus (GEO) database. OA-expressed ferroptosis-related genes were identified using Genecards data, differential gene analysis, and weighted gene co-expression network analysis. Enrichment analysis was utilized to identify signaling pathways and molecular mechanisms linked with ferroptosis in OA, while immune infiltration analysis indicated immune cell infiltration in OA. The action targets of resveratrol were taken from the TCM database to determine the therapeutic targets of resveratrol for the treatment of OA. To validate the molecular process, molecular docking was performed using the therapeutic targets' enrichment analysis. Finally, in vitro investigations confirmed the molecular mechanism of ferroptosis in resveratrol-treated OA. RESULTS Bioinformatic analysis identified 462 OA ferroptosis gene sets, with GPX4, TFRC, SLC7A11, EGFR, and IL1B serving as significant hub genes. Enrichment analysis revealed that ferroptosis was also linked to animal mitophagy, the FoxO signaling pathway, the Toll-like receptor signaling pathway, the PI3K-Akt signaling pathway, inflammation, immune response activation, and cellular autophagy. The immune infiltration data revealed that T_cells_CD4_memory_resting, T_cells_CD4_memory_activated, NK_cells_activated, and Mast_cells_activated were considerably infiltrated in OA. Resveratrol ameliorated OA via modulating autophagy and ferroptosis via GPX4, TFRC, SLC7A11, EGFR, and IL1B, according to a mechanistic study. CONCLUSION We discovered the mechanism of GPX4, TFRC, SLC7A11, and EGFR, IL1B ferroptosis-related genes in OA, and preliminary evidence suggests that resveratrol improves OA by regulating ferroptosis and immunological processes, which may give a new route for OA treatment.
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Affiliation(s)
- Chao Song
- Department of Orthopedics, RuiKang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning, Guangxi, China
| | - Baoxin Shen
- Department of Orthopedics, RuiKang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning, Guangxi, China
| | - Chaoqi Chen
- Department of Orthopedics, RuiKang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning, Guangxi, China
| | - Lei Yang
- Department of Orthopedics, RuiKang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning, Guangxi, China
| | - Chi Zhang
- Department of Orthopedics, RuiKang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning, Guangxi, China
| | - Fei Liu
- Department of Orthopedics, RuiKang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning, Guangxi, China
| | - Feng Chen
- Department of Orthopedics, RuiKang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning, Guangxi, China.
| | - Xiaofei Wu
- Department of Orthopedics, RuiKang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning, Guangxi, China.
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Andrag L, Derman W, Cockcroft J, Runciman P. Is biomechanical loading reduced in individuals with unilateral transtibial amputation during fast-paced walking when using different ankle/foot prostheses? A pragmatic randomized controlled trial. Prosthet Orthot Int 2025; 49:148-158. [PMID: 39486009 PMCID: PMC11984548 DOI: 10.1097/pxr.0000000000000395] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/22/2023] [Revised: 05/29/2024] [Accepted: 07/29/2024] [Indexed: 11/03/2024]
Abstract
INTRODUCTION Sound side loading is a risk factor for osteoarthritis development, which has been noted to reduce when using advanced prostheses during normal-paced walking in individuals with unilateral transtibial amputation (UTTA). However, descriptions of loading during fast-paced walking remain relatively unreported. Therefore, the aim of this study was to describe the biomechanical loading of individuals with UTTA while using different ankle/foot prostheses during fast-paced walking. METHODS A blinded, randomized control trial was conducted in a group of K3-K4 ambulators, who used 3 different prosthetic feet (1. a solid ankle cushioned heel foot prosthesis [SACH], 2. a standard energy storage and return foot prosthesis [ESAR], and 3. a novel ESAR foot prosthesis [N-ESAR]) in a 2-week randomized crossover design. The spatiotemporal and kinetic data of the participants' fast walking pace were collected. Data were analyzed using a mixed model and one-way analysis of variances ( p < 0.05) and Cohen d . RESULTS Twenty individuals with UTTA (age: 40 ± 16 years; height: 1.76 ± 0.09 m; and BMI: 24.72 ± 3.63 kg/m 2 ) participated in this study. There were minimal changes in the spatiotemporal data between the different prosthetic feet. When the participants used the N-ESAR feet, they had a lower peak vertical ground reaction force ( p = 0.02) and external knee adduction moment ( p = 0.02) on the sound side, as well as a higher distal shank power on the prosthetic side ( p < 0.01). CONCLUSION Overall fast-paced walking resulted in higher sound side loading forces compared with normal-paced walking. However, use of the N-ESAR prosthesis reduced the biomechanical loading on the sound side in individuals with UTTA while walking at a fast pace compared with the ESAR and SACH prostheses. The percentage change in the biomechanical loading from normal- to fast-paced walking of the N-ESAR foot was also larger compared with the other prostheses, perhaps because of the individuals' ability to achieve a faster walking pace when using the N-ESAR prosthesis. Longitudinal intervention studies should be performed to further investigate the possible benefits of using advanced prostheses.
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Affiliation(s)
- Lizanne Andrag
- Institute of Sport and Exercise Medicine (ISEM), Department of Exercise, Sport and Lifestyle Medicine, Faculty of Medicine and Health Sciences, Stellenbosch University, Stellenbosch, South Africa
| | - Wayne Derman
- Institute of Sport and Exercise Medicine (ISEM), Department of Exercise, Sport and Lifestyle Medicine, Faculty of Medicine and Health Sciences, Stellenbosch University, Stellenbosch, South Africa
- International Olympic Committee (IOC) Research Centre, Stellenbosch, South Africa
| | - John Cockcroft
- Institute of Sport and Exercise Medicine (ISEM), Department of Exercise, Sport and Lifestyle Medicine, Faculty of Medicine and Health Sciences, Stellenbosch University, Stellenbosch, South Africa
- Neuromechanics Unit, Central Analytics Facilities, Stellenbosch University, Stellenbosch, South Africa
| | - Phoebe Runciman
- Institute of Sport and Exercise Medicine (ISEM), Department of Exercise, Sport and Lifestyle Medicine, Faculty of Medicine and Health Sciences, Stellenbosch University, Stellenbosch, South Africa
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10
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Li Z, Dai A, Fang X, Tang K, Chen K, Gao P, Su J, Chen X, Yang S, Deng Z, Li L. The miR-6779/XIAP axis alleviates IL-1β-induced chondrocyte senescence and extracellular matrix loss in osteoarthritis. Animal Model Exp Med 2025; 8:662-673. [PMID: 39905808 PMCID: PMC12008434 DOI: 10.1002/ame2.12529] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2024] [Accepted: 12/10/2024] [Indexed: 02/06/2025] Open
Abstract
BACKGROUND Osteoarthritis (OA) is a long-term degenerative joint disease worsening over time. Aging and chondrocyte senescence contribute to OA progression. MicroRNAs have been confirmed to regulate different cellular processes. They contribute to OA pathology and may help to identify novel biomarkers and therapies for OA. METHODS This study used bioinformatics and experimental investigations to analyze and validate differentially expressed miRNAs in OA that might affect chondrocyte apoptosis and senescence. RESULTS miR-6779 was found to be significantly down-regulated in OA. Seventy-six of the predicted and miR-6779 targeted genes and the OA-associated disease genes overlapped, and these were enriched in cell proliferation, cell apoptosis, and cell cycle. miR-6779 overexpression remarkably attenuated IL-1β effects on chondrocytes by reducing MMP3 and MMP13 levels, promoting cell apoptosis, suppressing cell senescence, and increasing caspase-3, caspase-9 and reducing P16 and P21 levels. miR-6779 targeted inhibition of X-linked inhibitor of apoptosis protein (XIAP) expression. XIAP knockdown partially improved IL-1β-induced chondrocyte senescence and dysfunction. Lastly, when co-transfected with a miR-6779 agomir, the XIAP overexpression vector partially attenuated the effects of miR-6779 overexpression on chondrocytes; miR-6779 improved IL-1β-induced senescence and dysfunction in chondrocytes through targeting XIAP. CONCLUSION miR-6779 is down-regulated, and XIAP is up-regulated in OA cartilage and IL-1β-treated chondrocytes. miR-6779 inhibits XIAP expression, thereby promoting senescent chondrocyte cell apoptosis and reducing chondrocyte senescence and ECM loss through XIAP.
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Affiliation(s)
- Zongchao Li
- Department of Orthopaedics, The Affiliated Changsha Central Hospital, Hengyang Medical SchoolUniversity of South ChinaChangshaHunanChina
| | - Aonan Dai
- Department of Orthopaedics, The Affiliated Changsha Central Hospital, Hengyang Medical SchoolUniversity of South ChinaChangshaHunanChina
| | - Xiaoxiang Fang
- Department of Orthopaedics, The Affiliated Changsha Central Hospital, Hengyang Medical SchoolUniversity of South ChinaChangshaHunanChina
| | - Kexing Tang
- Department of Orthopaedics, The Affiliated Changsha Central Hospital, Hengyang Medical SchoolUniversity of South ChinaChangshaHunanChina
| | - Kun Chen
- Department of Orthopaedics, The Affiliated Changsha Central Hospital, Hengyang Medical SchoolUniversity of South ChinaChangshaHunanChina
| | - Peng Gao
- Department of Orthopaedics, The Affiliated Changsha Central Hospital, Hengyang Medical SchoolUniversity of South ChinaChangshaHunanChina
| | - Jingyue Su
- Department of Orthopaedic SurgeryThe First Affiliated Hospital of Wenzhou Medical UniversityWenzhouZhejiangChina
- Geriatrics CenterThe First Affiliated Hospital of Wenzhou Medical UniversityWenzhouZhejiangChina
| | - Xin Chen
- Department of Orthopaedic SurgeryThe First Affiliated Hospital of Wenzhou Medical UniversityWenzhouZhejiangChina
- Geriatrics CenterThe First Affiliated Hospital of Wenzhou Medical UniversityWenzhouZhejiangChina
| | - Shengwu Yang
- Department of Orthopaedic SurgeryThe First Affiliated Hospital of Wenzhou Medical UniversityWenzhouZhejiangChina
- Geriatrics CenterThe First Affiliated Hospital of Wenzhou Medical UniversityWenzhouZhejiangChina
| | - Zhenhan Deng
- Department of Orthopaedic SurgeryThe First Affiliated Hospital of Wenzhou Medical UniversityWenzhouZhejiangChina
- Geriatrics CenterThe First Affiliated Hospital of Wenzhou Medical UniversityWenzhouZhejiangChina
| | - Liangjun Li
- Department of Orthopaedics, The Affiliated Changsha Central Hospital, Hengyang Medical SchoolUniversity of South ChinaChangshaHunanChina
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11
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Zhu Z, Tu B, Peng C, Xu X, Lu P, Ning R. Integrated bioinformatics and clinical data identify three novel biomarkers for osteoarthritis diagnosis and synovial immune. Sci Rep 2025; 15:10987. [PMID: 40164659 PMCID: PMC11958655 DOI: 10.1038/s41598-025-95837-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2024] [Accepted: 03/24/2025] [Indexed: 04/02/2025] Open
Abstract
Osteoarthritis (OA) is a degenerative joint disease that can be aggravated by synovitis and synovial immune disorders (SID). However, the role of synovial SID-related genes in OA synovium remains poorly understood. OA synovial and peripheral blood datasets were obtained from the GEO database ( https://www.ncbi.nlm.nih.gov/ ). Immune-related genes ( https://reactome.org/ ) showing differential expression in peripheral blood were identified as immune disorder genes. Subsequently, differentially expressed immune disorder genes in OA synovium were further identified as SID genes. The Venn diagram, random forest, SVM-RFE algorithm, and multivariate analysis were employed to determine SID-related hub genes in OA synovium. Using the identified hub genes, we constructed and validated a diagnostic model for predicting OA occurrence. The correlation between hub gene expression and immune-related modules was explored using CIBERSORT and MCP-counter analyses. We identified three SID-related hub genes (ACAT1, SPHK1, and ACACB) in OA synovium. The diagnostic model incorporating these hub genes demonstrated reliable predictive accuracy (AUC = 0.939). Through qPCR analysis, we quantitated the expression levels of the hub genes and confirmed that three hub genes could serve as novel biomarkers for OA patients (AUC = 0.960). Furthermore, we observed a significant correlation between the expression of these hub genes and immune cell infiltration, as well as inflammatory cytokine levels in OA synovium. Our findings suggest that three SID-related hub genes have the potential to serve as diagnostic biomarkers for OA patients. These genes are associated with immune disorder and contribute to immune alterations within the OA synovium.
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Affiliation(s)
- Zheng Zhu
- Department of Orthopedics, Hefei First People's Hospital, Anhui Medical University, 390 Huaihe Road, Hefei, 230061, Anhui, China
| | - Bizhi Tu
- Department of Orthopedics, Hefei First People's Hospital, Anhui Medical University, 390 Huaihe Road, Hefei, 230061, Anhui, China
| | - Cheng Peng
- Department of Orthopedics, Hefei First People's Hospital, Anhui Medical University, 390 Huaihe Road, Hefei, 230061, Anhui, China
| | - Xun Xu
- Department of Orthopedics, Hefei First People's Hospital, Anhui Medical University, 390 Huaihe Road, Hefei, 230061, Anhui, China
| | - Peizhi Lu
- Department of Orthopedics, Hefei First People's Hospital, Anhui Medical University, 390 Huaihe Road, Hefei, 230061, Anhui, China
| | - Rende Ning
- Department of Orthopedics, Hefei First People's Hospital, Anhui Medical University, 390 Huaihe Road, Hefei, 230061, Anhui, China.
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12
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Bartsch A, Sherman SL, Tramer J, Vel MS, Fredericson M. Preserving Knee Health and Delivering Specialized Care for Active Older Athletes. Sports Health 2025:19417381251326527. [PMID: 40145656 PMCID: PMC11951129 DOI: 10.1177/19417381251326527] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/28/2025] Open
Abstract
CONTEXT Athletes differ from recreational exercisers in many characteristics and often require tailored treatments uniquely adapted to their situations and requirements. This practice is highlighted in young and middle-aged high-performance athletes. However, with advancing age and declining physical performance, age often outweighs athleticism, discounting the existing distinctions. This review focuses on physiological age-related processes in active older athletes and common knee conditions and elucidates the differences in preventing and treating knee injuries from the active adult population. EVIDENCE ACQUISITION Nonsystematic review with critical appraisal of existing literature. STUDY DESIGN Clinical review. LEVEL OF EVIDENCE Level 4. RESULTS Nonsteroidal anti-inflammatory drugs may interfere with the muscle hypertrophy mechanism in older athletes and it may be beneficial to adapt to other pharmacological interventions for knee osteoarthritis (OA). Arthroplasty is not typically compatible with high level sports activities; anterior cruciate ligament reconstruction surgery in the older athlete may be an effective option to improve function and enable return to sport, especially in the absence of OA. Chronic degenerative meniscal injuries can usually be treated conservatively, regardless of subjective mechanical symptoms. Acute traumatic meniscal tears in nonarthritic knees that cause effusions or reproducible mechanical symptoms may yet be considered for repair at any age. Conservative options are more dominant for patella tendinopathy, where platelet-rich plasma may be more effective than the classic extracorporeal shockwave therapy. CONCLUSION With the increase of the active older athletic population, prevention and injury treatment strategies must be balanced and tailored to their individual needs. Older athletes have various goals and demands in their respective sports, necessitating distinct prevention and treatment strategies.Strength of Recommendation Taxonomy (SORT):B.
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Affiliation(s)
- Anna Bartsch
- Department of Orthopaedic Surgery, Stanford University School of Medicine, Redwood City, California
- Department of Physical Medicine and Rehabilitation, Stanford University School of Medicine, Redwood City, California
- Department of Orthopedics and Trauma Surgery, University Hospital Basel, Basel, Switzerland
| | - Seth Lawrence Sherman
- Department of Orthopaedic Surgery, Stanford University School of Medicine, Redwood City, California
| | - Joseph Tramer
- Department of Orthopaedic Surgery, Cleveland Clinic Foundation, Garfield Heights, Ohio
| | - Monica Sri Vel
- Department of Orthopaedic Surgery, Stanford University School of Medicine, Redwood City, California
| | - Michael Fredericson
- Department of Orthopaedic Surgery, Stanford University School of Medicine, Redwood City, California
- Department of Physical Medicine and Rehabilitation, Stanford University School of Medicine, Redwood City, California
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13
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Geng M, Zhang K. CRP-Albumin-Lymphocyte index (CALLYI) as a risk-predicting biomarker in association with osteoarthritis. Arthritis Res Ther 2025; 27:57. [PMID: 40108660 PMCID: PMC11921634 DOI: 10.1186/s13075-025-03530-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2024] [Accepted: 03/10/2025] [Indexed: 03/22/2025] Open
Abstract
PURPOSE As a novel biomarker, the C-reactive protein-Albumin-Lymphocyte Index (CALLYI) offers a comprehensive evaluation of the human body from three perspectives. However, the association between CALLYI and the incidence of osteoarthritis (OA) remains unclear. This cross-sectional study investigates the potential relationship between CALLYI and OA in US adults, develops a clinical prediction model, and validates its effectiveness. METHOD The study cohort consisted of 18,624 U.S. adults who participated in the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2010. The CALLYI was calculated using the formula: albumin * lymphocytes / CRP * 10. Three weighted multiple regression models were constructed to investigate the correlation between CALLYI and OA. Restricted cubic splines (RCS) were employed to evaluate the nonlinear relationship between these two variables. Subgroup analyses were conducted to examine interactions. Univariate logistic regression, binary logistic regression, and least absolute shrinkage and selection operator (LASSO) were utilized for variable selection in the prediction model. Decision curve analysis (DCA) and receiver operating characteristic (ROC) curve analysis were applied to assess the predictive performance of the models. RESULTS The total sample size analyzed in this study was 18,624, of which 1,977 (10.62%) were diagnosed with OA. And the mean value of CALLYI was 5.13 (2.12,12.86). The multivariate logistic regression model revealed a negative correlation between elevated CALLYI and OA. The fully adjusted Model 3 demonstrated a significant 28% reduction in OA risk in the Q4 compared to the Q1 of CALLYI (OR = 0.72 95% CI: 0.59-0.88, p = 0.001). Subgroup analyses did not reveal any significant interactions (p > 0.05). Additionally, a significant non-linear relationship between CALLYI and OA using RCS (p < 0.0001). After variable screening, we constructed an OA prediction model incorporating CALLYI, and the results were visualized using a nomogram. The area under the curve (AUC) was 0.825 (95% CI: 0.817-0.834), and DCA indicated that the model holds clinical significance. CONCLUSION This study, utilizing NHANES statistics, is the first to establish a nonlinear negative relationship between CALLYI and OA, with no significant interaction observed in subgroup analyses. In the OA prediction model incorporating CALLYI, we validated the effectiveness and clinical utility of this model, providing evidence that CALLYI can serve as a biomarker for OA risk prediction. Nevertheless, larger multicenter prospective cohort studies are necessary to mitigate the limitations inherent in cross-sectional designs and self-reported OA diagnoses.
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Affiliation(s)
- Maosen Geng
- Department of Orthopedic, Xi'an Central Hospital, No. 161, West 5th Road, Xincheng District, Xi'an, Shaanxi, China
| | - Ke Zhang
- Department of Orthopedic, Xi'an Central Hospital, No. 161, West 5th Road, Xincheng District, Xi'an, Shaanxi, China.
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14
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Holm-Jensen A, Vlachos E, Storm LK, Myburgh C. The Consistency of Primary, Secondary and Tertiary Prevention Definitions in the Context of Musculoskeletal Sports Injuries: A Rapid Review and Critical Exploration of Common Terms of Usage. SPORTS MEDICINE - OPEN 2025; 11:28. [PMID: 40102364 PMCID: PMC11920493 DOI: 10.1186/s40798-025-00823-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/27/2024] [Accepted: 02/08/2025] [Indexed: 03/20/2025]
Abstract
BACKGROUND Formal statements articulating the meaning of primary, secondary and tertiary prevention concepts are commonly used in the musculoskeletal sports injuries literature, but appear to be employed inconsistently and incorrectly. Standard definitions, appropriate to athletic health and performance practice, are required to systematically develop the state-of-the-art. To accomplish this, we summarized prevention definitions with the aim of improving conceptual clarity across the musculoskeletal sports injuries literature. MAIN BODY We used a rapid literature review method, searching Scopus, PubMed/Medline, Cochrane Library reviews/trials, Web of Science, Sports Medicine and Education Index, SPORTDiscus and CINAHL databases for titles/abstracts for available literature, published in English from database-inception to November 2023. Our search terms were: sport/athlete, injury, primary prevention, secondary prevention, and/or tertiary prevention. Definitions were extracted to create categories illustrating overlap and variation. We extracted definitions from 144 included studies (n). Primary prevention appears focused on mitigating injury risk (n = 52) and preventing initial injuries (n = 42). Secondary prevention appears to address five distinct concepts: preventing recurrences (n = 42), preventing sequelae (n = 41), preventing index injury worsening (n = 27), mitigating injury risk (n = 15), and restoring function (n = 12). Tertiary prevention appears focused on preventing sequelae (n = 17) and restoring function (n = 9). CONCLUSIONS From a definition viewpoint, the aim of primary prevention is narrowly conceptualized and consistent in the musculoskeletal sports injury research literature. However, secondary prevention definitions vary substantially, with at least three distinct conceptual aims observable. Tertiary prevention definitions appear infrequently in the literature and when observed tend to overlap with secondary prevention. Currently, researchers are likely to struggle with the formulation of clearly-defined and transferrable research questions relating to the aims of secondary prevention.
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Affiliation(s)
- Aske Holm-Jensen
- Department of Sports Science and Clinical Biomechanics, University of Southern Denmark, Campusvej 55, Odense M, Denmark.
| | - Evgenios Vlachos
- University of Southern Denmark, University Library of Southern Denmark, Odense M, Denmark
- University of Southern Denmark, The Maersk Mc-Kinney Moller Institute, Odense M, Denmark
| | - Louise Kamuk Storm
- Department of Sports Science and Clinical Biomechanics, University of Southern Denmark, Campusvej 55, Odense M, Denmark
| | - Corrie Myburgh
- Department of Sports Science and Clinical Biomechanics, University of Southern Denmark, Campusvej 55, Odense M, Denmark
- The Chiropractic Knowledge Hub, University of Southern Denmark, Odense M, Denmark
- Department of Chiropractic, University of Johannesburg, Johannesburg, South Africa
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15
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Ito S, Igawa T, Iijima S, Ito A, Urata R, Ito R, Takahashi H, Suzuki K, Toda M, Hara T, Maruyama H. Effects of Walking Aids on Knee Adduction Moment After Total Knee Arthroplasty: A Gait Analysis Study. Cureus 2025; 17:e80828. [PMID: 40255838 PMCID: PMC12007936 DOI: 10.7759/cureus.80828] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/19/2025] [Indexed: 04/22/2025] Open
Abstract
BACKGROUND Total knee arthroplasty (TKA) is a common intervention for treating end-stage knee osteoarthritis (OA). Postoperatively, altered biomechanics may increase the risk of OA progression in the contralateral knee. Knee adduction moment (KAM) is a key indicator of medial knee joint loading and is associated with OA progression. Walking aids are often prescribed to reduce joint stress during walking; however, their comparative effects on KAM in patients undergoing TKA remain unclear. This study aimed to evaluate the effects of different walking aids (double canes [D-canes], rollators without forearm support [rollators], and rollators with forearm support [F-rollators]) on KAM peak and impulse in both the operated and contralateral knees of patients after TKA using gait analysis. METHODOLOGY A cross-sectional study was conducted on eight women who underwent unilateral TKA. Participants walked under four conditions: no aid, D-canes, rollators, and F-rollators. A three-dimensional motion capture system measured the lower limb kinematics and kinetics. The primary outcomes were KAM peak and impulse for both knees. Secondary outcomes included ground reaction force in the vertical direction (GRF Z), forward trunk tilt angle, and lower limb joint angles. A two-way repeated-measures measures analysis of variance (ANOVA) was used for statistical comparisons. RESULTS Walking aids significantly reduced the KAM peak and impulse in both the operated and contralateral knees compared with unaided walking (P < 0.001). In the operated knee, the KAM peak decreased by approximately 20% with all aids, whereas in the contralateral knee, reductions were 6% for D-canes, 16% for rollators, and 24% for F-rollators. Rollators and F-rollators more effectively reduced contralateral knee loading than D-canes (P < 0.001). A significant negative correlation was found between trunk forward tilt angle and GRF Z (ρ= -0.74, P < 0.001), suggesting that increased forward lean with rollators and F-rollators enhanced lower limb offloading. No significant changes were observed in knee varus angle or walking speed across conditions. CONCLUSIONS Walking aids, particularly F-rollators, effectively reduce KAM and offload the contralateral knee in patients after TKA. These findings suggest potential benefits for patients at risk of OA progression in non-operated knees.
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Affiliation(s)
- Shomaru Ito
- Department of Physical Therapy, School of Health Sciences, International University of Health and Welfare, Otawara, JPN
| | - Tatsuya Igawa
- Department of Physical Therapy, School of Health Sciences, International University of Health and Welfare, otawara, JPN
- Department of Physical Therapy, Graduate School, International University of Health and Welfare, Otawara, JPN
| | - Shinno Iijima
- Department of Physical Therapy, School of Health Sciences, International University of Health and Welfare, Otawara, JPN
| | - Akihiro Ito
- Department of Physical Therapy, School of Health Sciences, International University of Health and Welfare, Otawara, JPN
| | - Ryunosuke Urata
- Innovative Rehabilitation Center, New Spine Clinic, Tokyo, JPN
| | - Riyaka Ito
- Department of Physical Therapy, Graduate School, International University of Health and Welfare, Otawara, JPN
| | - Hiroto Takahashi
- Department of Physical Therapy, Graduate School, International University of Health and Welfare, Otawara, JPN
| | - Kosuke Suzuki
- Department of Rehabilitation, Yamagata Saisei Hospital, Yamagata, JPN
| | - Mika Toda
- Department of Physical Therapy, Graduate School, International University of Health and Welfare, Otawara, JPN
| | - Tsuyoshi Hara
- Department of Physical Therapy, School of Health Sciences, International University of Health and Welfare, Otawara, JPN
- Department of Physical Therapy, Graduate School, International University of Health and Welfare, Otawara, JPN
| | - Hitoshi Maruyama
- Department of Physical Therapy, Faculty of Medicine, Fukuoka International University of Health and Welfare, Fukuoka, JPN
- Department of Physical Therapy, Graduate School, International University of Health and Welfare, Otawara, JPN
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16
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Tanegashima G, Iidaka T, Muraki S, Horii C, Oka H, Kawaguchi H, Nakamura K, Akune T, Tanaka S, Yoshimura N. Trends in knee osteoarthritis prevalence over a 10-year period in Japan: The ROAD study 2005-2015. OSTEOARTHRITIS AND CARTILAGE OPEN 2025; 7:100569. [PMID: 39968102 PMCID: PMC11834036 DOI: 10.1016/j.ocarto.2025.100569] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2024] [Accepted: 01/20/2025] [Indexed: 02/20/2025] Open
Abstract
Objective This study aimed to clarify the trends in the prevalence of knee osteoarthritis (OA) and symptomatic knee OA among the general population using population-based cohort data from baseline and a survey 10 years later. Design The baseline survey of the Research on Osteoarthritis/Osteoporosis Against Disability (ROAD) study was conducted from 2005 to 2007; 3040 participants (1061 men and 1979 women; mean age 70.3 years) completed all OA examinations, including a questionnaire of medical information in the present/past and radiographic examination. The fourth survey was performed from 2015 to 2016; 2893 individuals (895 men and 1998 women, mean age 68.9 years) completed assessments identical to those at the baseline survey. Knee OA was defined using the Kellgren-Lawrence grading system. Results The prevalence of knee OA was 54.6 % (men, 42.0 %; women, 61.5 %) at the baseline survey and 39.3 % (men, 26.9 %; women, 44.9 %) at the fourth survey, with a significant decrease (p < 0.0001). The prevalence of symptomatic knee OA was 24.3 % (men, 16.9 %; women, 28.3 %) at the baseline survey and 20.6 % (men, 14.2 %; women, 23.5 %) at the fourth survey, showing a similar decrease (p < 0.0001). Thus, the prevalence of knee OA and symptomatic knee OA was lower at the fourth survey than at the baseline survey (p < 0.01). Conclusions In the population-based survey with a 10-year interval, the prevalence of knee OA and symptomatic knee OA decreased significantly. This preferable change in OA may suggest rejuvenation in the current population and could contribute to a decrease in the occurrence of disabilities in the future.
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Affiliation(s)
- Gaku Tanegashima
- Department of Orthopaedic Surgery, Sensory and Motor System Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, 113-8655, Japan
| | - Toshiko Iidaka
- Department of Prevention Medicine for Locomotive Organ Disorders, 22nd Century Medical and Research Center, The University of Tokyo, Tokyo, 113-8655, Japan
| | - Shigeyuki Muraki
- Department of Prevention Medicine for Locomotive Organ Disorders, 22nd Century Medical and Research Center, The University of Tokyo, Tokyo, 113-8655, Japan
| | - Chiaki Horii
- Department of Orthopaedic Surgery, Sensory and Motor System Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, 113-8655, Japan
| | - Hiroyuki Oka
- Division of Musculoskeletal AI System Development, Faculty of Medicine, The University of Tokyo, Tokyo, 113-8655, Japan
| | | | | | - Toru Akune
- National Rehabilitation Center for Persons with Disabilities, Saitama, 359-0042, Japan
| | - Sakae Tanaka
- Department of Orthopaedic Surgery, Sensory and Motor System Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, 113-8655, Japan
| | - Noriko Yoshimura
- Department of Prevention Medicine for Locomotive Organ Disorders, 22nd Century Medical and Research Center, The University of Tokyo, Tokyo, 113-8655, Japan
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17
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Drummen SJJ, Runhaar J, Bierma-Zeinstra SM, Aitken D, Jones G, Otahal P, Grønne DT, Roos EM, Skou ST. Early-stage vs established knee osteoarthritis: A comparative observational study on prevalence and changes in pain, function and quality of life after supervised exercise and education among 10,365 patients. Osteoarthritis Cartilage 2025; 33:364-372. [PMID: 39617203 DOI: 10.1016/j.joca.2024.11.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/04/2024] [Revised: 11/03/2024] [Accepted: 11/05/2024] [Indexed: 12/09/2024]
Abstract
OBJECTIVE Compare prevalence and changes in outcomes among established and early-stage knee osteoarthritis (KOA) patients undertaking supervised exercise and education. METHODS Patients from Good Life with osteoArthritis in Denmark (GLA:D®) were stratified into three groups: established KOA (ACR/EULAR criteria), early-stage KOA (diagnostic-model-outcome ≥70%, Criteria for the Early Diagnosis of knee Osteoarthritis) or potential early-stage KOA (diagnostic-model-outcome 30-69%). Mixed-effects models and the proportion of patients by group achieving minimal clinically important improvements (MCIIs) were used to investigate changes in VAS pain intensity (0-100mm), Knee injury and Osteoarthritis Outcome Score (KOOS) Quality of Life (QoL; 0-100), 40 m Walk test and 30 s chair-stand test at 3 and 12 months. RESULTS Compared to established KOA (61% of 10,365 patients), early-stage KOA (27%) had similar knee pain at baseline (mean (standard deviation); 51 (22) vs 45 (22)), and improvement in pain (mean (95% confidence interval) -15 (-15 to -14) vs -14 (-15 to -13), ≥MCII: 55% vs 54%) and KOOS QoL (≥MCII: 50% vs 50%) at 12 months, and in walking speed (≥MCII: 56% vs 52%) and chair-stands (≥MCII: 55% vs 52%) at 3 months. Compared to either group, potential early-stage KOA (10%) had lower baseline pain (34 (32.7)) and less improvement in pain (-9.8 (-11.3 to -8.2; ≥MCII: 47%)), but comparable improvements in KOOS QoL (≥MCII: 50%), walking speed (≥MCII: 51%) and chair-stands (≥MCII: 51%). CONCLUSION Patients with early-stage KOA achieved comparable improvements at 3 and 12 months to those with established KOA, supporting supervised exercise and education as a viable management strategy for early-stage KOA.
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Affiliation(s)
- S J J Drummen
- Menzies Institute for Medical Research, University of Tasmania, Hobart, Australia; Department of General Practice, Erasmus MC University Medical Center Rotterdam, Rotterdam, the Netherlands.
| | - J Runhaar
- Department of General Practice, Erasmus MC University Medical Center Rotterdam, Rotterdam, the Netherlands
| | - S M Bierma-Zeinstra
- Department of General Practice, Erasmus MC University Medical Center Rotterdam, Rotterdam, the Netherlands; Department of Orthopaedic Surgery and Sports Medicine, Erasmus MC University Medical Center Rotterdam, Rotterdam, the Netherlands
| | - D Aitken
- Menzies Institute for Medical Research, University of Tasmania, Hobart, Australia
| | - G Jones
- Menzies Institute for Medical Research, University of Tasmania, Hobart, Australia
| | - P Otahal
- Menzies Institute for Medical Research, University of Tasmania, Hobart, Australia
| | - D T Grønne
- Center for Muscle and Joint Health, Department of Sports Science and Clinical Biomechanics, University of Southern Denmark, Odense, Denmark; The Research and Implementation Unit PROgrez, Department of Physiotherapy and Occupational Therapy, Næstved-Slagelse-Ringsted Hospitals, Region Zealand, Slagelse, Denmark
| | - E M Roos
- Center for Muscle and Joint Health, Department of Sports Science and Clinical Biomechanics, University of Southern Denmark, Odense, Denmark
| | - S T Skou
- Center for Muscle and Joint Health, Department of Sports Science and Clinical Biomechanics, University of Southern Denmark, Odense, Denmark; The Research and Implementation Unit PROgrez, Department of Physiotherapy and Occupational Therapy, Næstved-Slagelse-Ringsted Hospitals, Region Zealand, Slagelse, Denmark
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18
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Tang S, Zhang C, Oo WM, Fu K, Risberg MA, Bierma-Zeinstra SM, Neogi T, Atukorala I, Malfait AM, Ding C, Hunter DJ. Osteoarthritis. Nat Rev Dis Primers 2025; 11:10. [PMID: 39948092 DOI: 10.1038/s41572-025-00594-6] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 01/10/2025] [Indexed: 05/09/2025]
Abstract
Osteoarthritis is a heterogeneous whole-joint disease that can cause pain and is a leading cause of disability and premature work loss. The predominant disease risk factors - obesity and joint injury - are well recognized and modifiable. A greater understanding of the complex mechanisms, including inflammatory, metabolic and post-traumatic processes, that can lead to disease and of the pathophysiology of pain is helping to delineate mechanistic targets. Currently, management is primarily focused on alleviating the main symptoms of pain and obstructed function through lifestyle interventions such as self-management programmes, education, physical activity, exercise and weight management. However, lack of adherence to known effective osteoarthritis therapeutic strategies also contributes to the high global disease burden. For those who have persistent symptoms that are compromising quality of life and have not responded adequately to core treatments, joint replacement is an option to consider. The burden imparted by the disease causes a substantial impact on individuals affected in terms of quality of life. For society, this disease is a substantial driver of increased health-care costs and underemployment. This Primer highlights advances and controversies in osteoarthritis, drawing key insights from the current evidence base.
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Affiliation(s)
- Su'an Tang
- Clinical Research Centre, Zhujiang Hospital, Southern Medical University, Guangzhou, China
- Department of Spinal Surgery, Orthopedic Medical Center, Zhujiang Hospital, Southern Medical University, Guangzhou, China
- Institute of Exercise and Rehabilitation Science, Zhujiang Hospital, Southern Medical University, Guangzhou, China
| | - Changqing Zhang
- Department of Orthopedic Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Win Min Oo
- Department of Rheumatology, Royal North Shore Hospital and Sydney Musculoskeletal Health, Faculty of Medicine and Health Science, Kolling Institute, University of Sydney, Sydney, Australia
- Department of Physical Medicine and Rehabilitation, Mandalay General Hospital, University of Medicine, Mandalay, Myanmar
| | - Kai Fu
- Department of Orthopedic Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - May Arna Risberg
- Department of Sport Medicine, Norwegian School Sport Sciences, Oslo, Norway
| | - Sita M Bierma-Zeinstra
- Department of General Practice, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Tuhina Neogi
- Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA
| | - Inoshi Atukorala
- Department of Clinical Medicine, Faculty of Medicine, University of Colombo, Colombo, Sri Lanka
| | - Anne-Marie Malfait
- Department of Internal Medicine, Division of Rheumatology, Rush University Medical Center, Chicago, IL, USA
| | - Changhai Ding
- Clinical Research Centre, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
- Institute of Exercise and Rehabilitation Science, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
- Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia.
| | - David J Hunter
- Clinical Research Centre, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
- Department of Orthopedic Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
- Department of Rheumatology, Royal North Shore Hospital and Sydney Musculoskeletal Health, Faculty of Medicine and Health Science, Kolling Institute, University of Sydney, Sydney, Australia.
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19
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Bugeja JM, Pagnozzi AM. Editorial for "Reproducibility of Quantitative Double-Echo Steady-State T 2 Mapping of Knee Cartilage". J Magn Reson Imaging 2025; 61:796-797. [PMID: 38733372 DOI: 10.1002/jmri.29448] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2024] [Accepted: 04/02/2024] [Indexed: 05/13/2024] Open
Affiliation(s)
- Jessica M Bugeja
- The Australian e-Health Research Centre, Health and Biosecurity, Commonwealth Scientific and Industrial Research Organisation, Brisbane, Queensland, Australia
| | - Alex M Pagnozzi
- The Australian e-Health Research Centre, Health and Biosecurity, Commonwealth Scientific and Industrial Research Organisation, Brisbane, Queensland, Australia
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20
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Lynch DH, Petersen CL, Stewart D, Justice JN, Batchek DJ, Sumner S, McRitchie S, Batsis JA. Changes in senescence markers after a weight loss intervention in older adults with obesity. Arch Gerontol Geriatr 2025; 129:105685. [PMID: 39541752 PMCID: PMC11616393 DOI: 10.1016/j.archger.2024.105685] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2023] [Revised: 11/01/2024] [Accepted: 11/04/2024] [Indexed: 11/16/2024]
Abstract
BACKGROUND Understanding how weight loss interventions in older adults with obesity impact aging biology can lay the foundation for targeted, 'geroscience-based' interventions. This study examines the association between changes in the senescence-associated secretory phenotypes (SASP) and changes in function in response to a weight loss intervention. METHODS We conducted a post-hoc biomarker analysis on adults aged ≥ 65 years with body mass index [BMI] ≥30 kg/m2 enrolled in a six-month, non-randomized telemedicine-delivered weight loss intervention. We assessed 16 SASP cytokines using serum samples collected pre-and post-intervention. Clinical outcomes include anthropometric and physical function measurements. A weight loss responder was defined as a loss of ≥5 % of body weight. RESULTS Mean age was 73.2 ± 3.9 years (73 % female), and BMI was 36.5 ± 5.2 kg/m2. Responders lost 7.6 ± 2.5 %, while non-responders lost 2.0 ± 2.3 % of weight (n = 16 per group, p < 0.001). We observed several significant associations between SASP cytokines and physical function and anthropometric measurement outcomes in age- and sex-adjusted linear models. These included grip strength and Interleukin-8 (IL-8) (b = 9.07) and Insulin-like Growth Factor 1 (IGF-1) (b = 2.6); gait speed and Thymus and Activation-Regulated Chemokine (TARC) (b = 0.46) and IL-7(b = 61 0.11); weight IL-6 (b = -6.77) and IL-15 (b = -2.53); BMI and IL-15 (b = -0.95); waist-to-hip ratio and osteopontin (b = -0.07) (p < 0.05 for all). CONCLUSIONS Our pilot data demonstrated an association between changes in select SASP biomarkers and increased functional ability with intentional weight loss in older adults with obesity. However, findings must be replicated in prospective randomized trials with a control group and additional SASP biomarkers.
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Affiliation(s)
- David H Lynch
- Division of Geriatric Medicine and Center for Aging and Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States.
| | - Curtis L Petersen
- Geisel School of Medicine, and The Dartmouth Institute for Health Policy, Hanover, New Hampshire, United States
| | - Delisha Stewart
- Nutrition Research Institute, Department of Nutrition, University of North Carolina, Kannapolis, North Carolina, United States
| | - Jamie N Justice
- Division of Gerontology and Geriatric Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina, United States
| | - Dakota J Batchek
- Division of Geriatric Medicine and Center for Aging and Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States
| | - Susan Sumner
- Nutrition Research Institute, Department of Nutrition, University of North Carolina, Kannapolis, North Carolina, United States
| | - Susan McRitchie
- Nutrition Research Institute, Department of Nutrition, University of North Carolina, Kannapolis, North Carolina, United States
| | - John A Batsis
- Division of Geriatric Medicine and Center for Aging and Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States; Department of Nutrition, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States
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21
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Chen Y, Lin J, Lin J, Gao T, Cai Q, Zhang C, Zhu H, Shen L, Wang Q. Comparison of the effectiveness of intra-infrapatellar fat pad and intra-articular glucocorticoid injection in knee osteoarthritis patients with Hoffa's synovitis: protocol for a multicentre randomised controlled trial. BMJ Open 2025; 15:e087785. [PMID: 39880431 PMCID: PMC11781145 DOI: 10.1136/bmjopen-2024-087785] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/19/2024] [Accepted: 12/30/2024] [Indexed: 01/31/2025] Open
Abstract
INTRODUCTION The infrapatellar fat pad and synovium are the sites of immune cell infiltration and the origin of proinflammation. Studies have shown that Hoffa's synovitis may be a sign of early-stage osteoarthritis (OA). However, there have been no effective interventions specifically for Hoffa's synovitis. METHODS AND ANALYSIS We will conduct a multicentre, multi-blind (participant, physician, outcome assessor and data analyst blinded) randomised controlled trial to compare the effectiveness of an intra-infrapatellar fat glucocorticoid versus an intra-articular injection for Hoffa's synovitis in patients with knee OA. We will recruit 236 knee OA patients with Hoffa's synovitis at outpatient clinics in three centres. We will randomly allocate them to two groups in a 1:1 ratio. One group will receive ultrasound-guided injection of 40 mg (1 mL) triamcinolone acetonide into the infrapatellar fat pad; the other group will receive ultrasound-guided injection of 40 mg (1 mL) triamcinolone acetonide into the knee joint cavity. All patients will be followed up at 2, 4, 8, 12 and 24 weeks after the injection. Primary outcomes are (1) Hoffa's synovitis improvement rate, measured with the MRI Osteoarthritis Knee Score system (superiority outcome) at 24 weeks and (2) pain intensity, measured with the Western Ontario and McMasters University Osteoarthritis Index (WOMAC) at 2 weeks post-injection. Secondary outcomes include Hoffa's synovitis score at 2 weeks post-injection, pain intensity with the numerical rating scale, WOMAC questionnaire score improvements (function, joint stiffness and total score), improvement rates in effusion synovitis at 2 and 24 weeks, articular cartilage thickness changes at 2 and 24 weeks, Intermittent and Constant Osteoarthritis Pain score, quality of life measured with the EuroQol-5D, OARSI-OMERACT response indicators, co-interventions and side effects at 2, 4, 8, 12 and 24 weeks. ETHICS AND DISSEMINATION Ethical approval has been granted by the Medical Ethics Committee of the Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (2023-178). Written informed consent will be obtained from all patients prior to data collection. The findings of this research will be shared through presentations at academic conferences and publications in peer-reviewed journals. TRIAL REGISTRATION NUMBER ChiCTR2400080474.
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Affiliation(s)
- Yiwei Chen
- Department of Orthopaedics, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Institute of Microsurgery on Extremities, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Junqing Lin
- Department of Orthopaedics, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Institute of Microsurgery on Extremities, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jiali Lin
- Shanghai Medical college, Fudan university, Shanghai, China
| | - Tao Gao
- Department of Orthopaedics, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Institute of Microsurgery on Extremities, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Qianying Cai
- Department of Orthopaedics, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Institute of Microsurgery on Extremities, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Changqing Zhang
- Department of Orthopaedics, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Institute of Microsurgery on Extremities, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Hongyi Zhu
- Department of Orthopaedics, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Institute of Microsurgery on Extremities, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Longxiang Shen
- Department of Orthopaedics, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Institute of Microsurgery on Extremities, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Qiuke Wang
- Department of Orthopaedics, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Institute of Microsurgery on Extremities, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
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22
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Sun YY, Wang ML, Zhao RH, Hao MY, Song S, Zhou Y, Zhang N. The Efficacy and Brain Network Mechanism of Acupuncture for Knee Osteoarthritis: A Study Protocol for Randomized Controlled Neuroimaging Trial. J Pain Res 2025; 18:391-404. [PMID: 39872091 PMCID: PMC11771175 DOI: 10.2147/jpr.s500024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2024] [Accepted: 01/07/2025] [Indexed: 01/29/2025] Open
Abstract
Purpose Knee osteoarthritis (KOA) is a prevalent degenerative bone and joint disease observed in clinical practice. While acupuncture has demonstrated efficacy in treating KOA, the central mechanisms underlying its effects remain ambiguous. Recently, functional magnetic resonance imaging (fMRI) has been extensively applied in studying the brain mechanisms of acupuncture analgesia. Currently, network analysis based on brain connectomics is a focal point in acupuncture imaging research. Therefore, this study uses KOA as the research vehicle, focuses on the abnormal connectivity patterns of brain functional networks, and integrates clinical pain assessments to thoroughly investigate the central mechanisms of acupuncture therapeutic effects on KOA. Patients and Methods In this parallel, randomized, sham-controlled neuroimaging trial, 60 KOA patients will be randomly divided into the acupuncture group and sham acupuncture group in a 1:1 ratio, treated three times weekly for a total of 12 sessions. Patients will undergo clinical symptom assessments and cranial fMRI scans at baseline (-1-0 weeks), post-treatment (4 weeks), and at the follow-up (16 weeks). Forty healthy subjects will be recruited for observation, with a single MRI scan conducted only at baseline (-1-0 week). The primary efficacy indicator will be the change in NRS score after four weeks of treatment, with secondary outcomes including WOMAC, STAI, and safety assessments. fMRI observations will employ independent component analysis, brain network construction, and functional connectivity, complemented by Pearson correlation analysis to explore the relationship between brain responses and clinical improvements. Conclusion This study will initially uncover how acupuncture intervention for chronic KOA pain centrally regulates and exerts therapeutic effects through the modulation of abnormal brain network functional connectivity patterns, with a demonstrated long-term effect. Ethics and Dissemination This study has been approved by the ethics committee of Shandong University of Traditional Chinese Medicine Affiliated Hospital ((2024) Lunshen No. (028) - KY). Clinical Trial Registration This study has been approved by registered in the Chinese Clinical Trial Registry (ChiCTR2400083695).
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Affiliation(s)
- Yi-Yang Sun
- Department of Acupuncture-Moxibustion and Tuina, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, People’s Republic of China
| | - Ming-Lin Wang
- Traditional Chinese Medicine Comprehensive Treatment Center, Shengli Oilfield Central Hospital, Jinan, Shandong, People’s Republic of China
| | - Ruo-Han Zhao
- Department of Acupuncture-Moxibustion and Tuina, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, People’s Republic of China
| | - Ming-Yao Hao
- External Treatment Center of Traditional Chinese Medicine, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong, People’s Republic of China
| | - Shuai Song
- External Treatment Center of Traditional Chinese Medicine, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong, People’s Republic of China
| | - Yue Zhou
- External Treatment Center of Traditional Chinese Medicine, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong, People’s Republic of China
| | - Na Zhang
- Department of Acupuncture-Moxibustion and Tuina, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, People’s Republic of China
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23
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Zhang D, Ye M, Xu Y, Jiang L, Hu Y, Zhang Q, Han X, Dai Q, Qian J, Luo J, Yuan Q. Shining light on knee osteoarthritis: an overview of vitamin D supplementation studies. Front Med (Lausanne) 2025; 11:1423360. [PMID: 39931432 PMCID: PMC11809650 DOI: 10.3389/fmed.2024.1423360] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2024] [Accepted: 12/19/2024] [Indexed: 02/13/2025] Open
Abstract
Background The impact of knee osteoarthritis on individuals' daily functioning is significant. In recent years, Vitamin D supplements cure osteoarthritis has garnered attention from medical professionals and patients due to its simplicity and portability. Several systematic reviews (SRs) and meta-analyses (MAs) have examined the efficacy of vitamin D supplementation for knee osteoarthritis, yet there is variability in their methodology and quality. Objective To search, gather, and analyze data on the characteristics and quantitative results of SR/MA in patients with KOA treated with Vitamin D supplementation, and objectively evaluate the efficacy of supplements. Then, provides clinical evidence and recommendations the clinical use of vitamin D supplementation. Methods Two individuals reviewed and collected data from four databases until October 2023. AMSTAR-2, ROBIS, PRISMA 2020, and GRADE tools were used to evaluate the methodological quality, bias risk, reporting quality, and evidence strength of all SR/MA. Additionally, we applied the corrected covered area (CCA) method to measure overlap in randomized controlled trials (RCTs) cited among the SR/MA. Results 3 SRs and 6 MAs were included in the analysis: 3 studies were low quality by AMSTAR-2, and 6 studies were very low quality. According to ROBIS, 6 studies were high-risk and 3 were low-risk. In PRISMA 2020 reporting quality, most studies showed deficiencies in comprehensive literature search strategy, reasons for literature exclusion, data preprocessing for meta-analysis, exploration of reasons for heterogeneity, sensitivity analysis, publication bias, and disclosure of funding and conflicts of interest. Grading the quality of evidence in GRADE consisted of 5 items of moderate quality, 14 items of low quality, and 10 items of very low quality. Bias risk and imprecision were the main factors for downgrading. The calculation of RCT overlap between SR/MA using CCA showed a high degree of overlap. Conclusion Vitamin D supplementation may show potential efficacy in ameliorating symptoms of KOA. The evidence indicates that Vitamin D supplements for knee osteoarthritis can improve patients' Total WOMAC scores and synovial fluid volume in the joints. Nevertheless, due to the generally low quality of current studies, future research should prioritize improving the quality of primary studies to establish the efficacy of vitamin D supplementation for KOA with more robust scientific evidence. Systematic review registration The protocol of this overview was registered in the International Prospective Register of Systematic Reviews (PROSPERO) (https://www.crd.york.ac.uk/PROSPERO/) with the registration number CRD42024535841.
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Affiliation(s)
- Di Zhang
- School of Acupuncture and Tuina, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Miaoyu Ye
- School of Acupuncture and Tuina, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Yao Xu
- Department of Tuina, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Luyu Jiang
- School of Acupuncture and Tuina, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Yanmei Hu
- School of Acupuncture and Tuina, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Qi Zhang
- School of Acupuncture and Tuina, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Xiao Han
- School of Acupuncture and Tuina, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Qian Dai
- School of Acupuncture and Tuina, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Junhui Qian
- Department of Tuina, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Jian Luo
- Department of Tuina, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Qiang Yuan
- Department of Tuina, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
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24
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Mizuno Y, Takata Y, Shima Y, Goshima K, Kuroda K, Kanayama T, Ishida Y, Takemoto N, Nishimura M, Sengoku T, Demura S, Nakase J. Relationship between ultrasonographic findings and subscales of the Knee Injury and Osteoarthritis Outcome Score in patients with early knee osteoarthritis: a multicenter study. J Med Ultrason (2001) 2025; 52:139-148. [PMID: 39322823 DOI: 10.1007/s10396-024-01498-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2024] [Accepted: 08/16/2024] [Indexed: 09/27/2024]
Abstract
PURPOSE To characterize the ultrasonographic findings of patients with early knee osteoarthritis (KOA) and determine which findings were associated with the Knee Injury and Osteoarthritis Outcome Score (KOOS) subscale. METHODS The study included 98 knees (35 men, 63 women, 60.3 ± 11.5 years) diagnosed with early KOA with no major deformity radiographically, but with pain during activity and tenderness in the medial knee. Synovial hyperplasia in the suprapatellar bursa, knee joint effusion, horizontal tear of the medial meniscus (MM), osteophytes of the medial condyle of the femur and tibia, blood flow signals in the synovium of the suprapatellar bursa, medial collateral ligament bursa, infrapatellar fat pad, MM extrusion (MME) in the supine and upright positions, and the amount of change in MME were observed using ultrasonography. RESULTS Correlations (p < 0.05) were found between the presence of synovial hyperplasia of the suprapatellar bursa (r<-0.20) and amount of MME in the upright position (r< - 0.24) and all KOOS subscales. Presence of joint effusion and the four KOOS subscales except quality of life (QOL) were correlated (p < 0.05). Partial correlation coefficients showed correlations (p < 0.05) between knee joint effusion and symptoms (r = 0.299) and activities of daily living (ADL) (r = 0.254) of the KOOS subscales, and between MME in the upright position and symptoms (r= - 0.263), pain (r= - 0.256), and ADL (r= - 0.212). CONCLUSION Quality and difficulty of life of patients with early KOA may be influenced by synovial hyperplasia in the suprapatellar bursa, joint effusion, and MME values in the upright position. Among them, synovial hyperplasia of the suprapatellar bursa and amount of MME in the upright position were independently associated with the KOOS subscales.
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Affiliation(s)
- Yushin Mizuno
- Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kanazawa University, 13-1 Takaramachi, Kanazawa, Ishikawa, 920-8641, Japan.
- Section of Rehabilitation, Kanazawa University Hospital, Kanazawa, Ishikawa, Japan.
| | - Yasushi Takata
- Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kanazawa University, 13-1 Takaramachi, Kanazawa, Ishikawa, 920-8641, Japan
| | - Yosuke Shima
- Department of Orthopaedic Surgery, KKR Hokuriku Hospital, Kanazawa, Ishikawa, Japan
| | - Kenichi Goshima
- Department of Orthopaedic Surgery and Joint Reconstructive Surgery, Kanazawa Munehiro Hospital, Kanazawa, Ishikawa, Japan
| | - Kazunari Kuroda
- Department of Orthopaedic Surgery, Yawata Medical Center, Komatsu, Ishikawa, Japan
| | - Tomoyuki Kanayama
- Department of Orthopaedic Surgery, KKR Hokuriku Hospital, Kanazawa, Ishikawa, Japan
| | - Yoshihiro Ishida
- Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kanazawa University, 13-1 Takaramachi, Kanazawa, Ishikawa, 920-8641, Japan
| | - Naoki Takemoto
- Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kanazawa University, 13-1 Takaramachi, Kanazawa, Ishikawa, 920-8641, Japan
| | - Manase Nishimura
- Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kanazawa University, 13-1 Takaramachi, Kanazawa, Ishikawa, 920-8641, Japan
| | - Takuya Sengoku
- Section of Rehabilitation, Kanazawa University Hospital, Kanazawa, Ishikawa, Japan
| | - Satoru Demura
- Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kanazawa University, 13-1 Takaramachi, Kanazawa, Ishikawa, 920-8641, Japan
| | - Junsuke Nakase
- Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kanazawa University, 13-1 Takaramachi, Kanazawa, Ishikawa, 920-8641, Japan
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25
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Hanrahan CJ. Editorial for "Associating Knee Osteoarthritis Progression with Temporal-Regional Graph Convolutional Network Analysis on MR Images". J Magn Reson Imaging 2025; 61:392-393. [PMID: 38713016 DOI: 10.1002/jmri.29440] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2024] [Accepted: 04/24/2024] [Indexed: 05/08/2024] Open
Affiliation(s)
- Christopher J Hanrahan
- Intermountain Healthcare, Adjunct Associate Professor of Radiology and Imaging Sciences, University of Utah School of Medicine, Salt Lake City, Utah, USA
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26
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Wang D, Liu W, Venkatesan JK, Madry H, Cucchiarini M. Therapeutic Controlled Release Strategies for Human Osteoarthritis. Adv Healthc Mater 2025; 14:e2402737. [PMID: 39506433 PMCID: PMC11730424 DOI: 10.1002/adhm.202402737] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2024] [Revised: 10/15/2024] [Indexed: 11/08/2024]
Abstract
Osteoarthritis is a progressive, irreversible debilitating whole joint disease that affects millions of people worldwide. Despite the availability of various options (non-pharmacological and pharmacological treatments and therapy, orthobiologics, and surgical interventions), none of them can definitively cure osteoarthritis in patients. Strategies based on the controlled release of therapeutic compounds via biocompatible materials may provide powerful tools to enhance the spatiotemporal delivery, expression, and activities of the candidate agents as a means to durably manage the pathological progression of osteoarthritis in the affected joints upon convenient intra-articular (injectable) delivery while reducing their clearance, dissemination, or side effects. The goal of this review is to describe the current knowledge and advancements of controlled release to treat osteoarthritis, from basic principles to applications in vivo using therapeutic recombinant molecules and drugs and more innovatively gene sequences, providing a degree of confidence to manage the disease in patients in a close future.
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Affiliation(s)
- Dan Wang
- Center of Experimental OrthopaedicsSaarland University and Saarland University Medical CenterKirrbergerstr. Bldg 37D‐66421Homburg/SaarGermany
| | - Wei Liu
- Center of Experimental OrthopaedicsSaarland University and Saarland University Medical CenterKirrbergerstr. Bldg 37D‐66421Homburg/SaarGermany
| | - Jagadeesh K. Venkatesan
- Center of Experimental OrthopaedicsSaarland University and Saarland University Medical CenterKirrbergerstr. Bldg 37D‐66421Homburg/SaarGermany
| | - Henning Madry
- Center of Experimental OrthopaedicsSaarland University and Saarland University Medical CenterKirrbergerstr. Bldg 37D‐66421Homburg/SaarGermany
| | - Magali Cucchiarini
- Center of Experimental OrthopaedicsSaarland University and Saarland University Medical CenterKirrbergerstr. Bldg 37D‐66421Homburg/SaarGermany
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27
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Lee BW, Lee JJ, Jung JY, Ju JH. Intra-Articular Injection of Human Bone Marrow-Derived Mesenchymal Stem Cells in Knee Osteoarthritis: A Randomized, Double-Blind, Controlled Trial. Cell Transplant 2025; 34:9636897241303275. [PMID: 39874108 PMCID: PMC11775978 DOI: 10.1177/09636897241303275] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2024] [Revised: 11/04/2024] [Accepted: 11/11/2024] [Indexed: 01/30/2025] Open
Abstract
To assess the impact of a single intra-articular (IA) injection of bone marrow-derived mesenchymal stem cells (BM-MSCs) in patients with knee osteoarthritis (OA), a randomized, double-blind, placebo-controlled study was conducted. The study included 24 patients with knee OA who were randomly assigned to receive either a single IA injection of BM-MSCs or normal saline. Changes in the visual analog scale (VAS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and Knee Injury and Osteoarthritis Outcome Score (KOOS) after IA injection were assessed at 3, 6, 9, and 12 months. Magnetic resonance imaging (MRI) with T2 mapping sequences was conducted for knee cartilage assessment at baseline and at 3 and 12 months. The MSC group showed between-group improvement in WOMAC (-5.0 ± 3.6 vs. -0.1 ± 5.5, P = 0.02) and KOOS (23.9 ± 18.3 vs. 7.2 ± 15.9, P = 0.028) scores at 9 months compared with the control group. The MSC group exhibited a less sharp increase in the mean T2 value of the medial compartment than the control group at 12 months, with no serious adverse events observed during follow-up. A single IA injection of allogeneic BM-MSCs provided satisfactory pain relief for patients with knee OA compared with the control group at 9 months. Quantitative T2 MRI mapping of the cartilage showed that IA BM-MSCs could have a preventive effect on OA progression for 12 months. Our findings suggest the potential of allogeneic BM-MSCs IA injection as a pain-relieving and disease-modifying treatment for patients with knee OA in the outpatient setting.
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Affiliation(s)
- Bong-Woo Lee
- Division of Rheumatology, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Jennifer Jooha Lee
- Division of Rheumatology, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Joon-Yong Jung
- Department of Radiology, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Ji Hyeon Ju
- Division of Rheumatology, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
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28
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Yu TC, Wu WT, Lee RP, Chen IH, Wang JH, Wen SH, Yeh KT. Incidence of Total Knee Arthroplasty in Older Females with Knee Osteoarthritis and Osteoporosis Treated with Denosumab Compared with Those Treated Using Bisphosphonates: A Population-Based Cohort Study. Life (Basel) 2024; 14:1704. [PMID: 39768410 PMCID: PMC11677198 DOI: 10.3390/life14121704] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2024] [Revised: 12/09/2024] [Accepted: 12/19/2024] [Indexed: 01/11/2025] Open
Abstract
This study aimed to evaluate the incidence of total knee arthroplasty (TKA), a marker of severe knee osteoarthritis (OA), among older females with concurrent knee OA and osteoporosis (OP) who were treated with denosumab or bisphosphonates. By analyzing a large population-based cohort, we sought to clarify how these treatments influence the progression of knee OA to the point of requiring surgical intervention. We used data from the Taiwan National Health Insurance Research Database, including data from females aged ≥ 50 years diagnosed with knee OA and OP who initiated treatment between 2012 and 2019. Propensity score matching (1:1) resulted in the selection of 13,774 patients (6897 per group). The TKA incidence was analyzed using Cox proportional hazards models. Patients treated with denosumab had a lower TKA incidence than those treated with bisphosphonates (6.9 vs. 8.5 per 1000 person-years). The adjusted hazard ratio (aHR) for TKA in the denosumab group was 0.77 (95% CI: 0.62-0.97; p = 0.024), with the most pronounced effect observed in patients aged ≥ 80 years (aHR = 0.39, 95% CI: 0.20-0.77; p = 0.007). These findings suggest that denosumab reduces TKA risk more effectively than bisphosphonates and may serve as a superior treatment option for mitigating severe knee OA progression, especially in older adults.
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Affiliation(s)
- Tzai-Chiu Yu
- Department of Orthopedics, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien 970473, Taiwan; (T.-C.Y.); (W.-T.W.); (I.-H.C.)
- Institute of Medical Sciences, Tzu Chi University, Hualien 970374, Taiwan;
- School of Medicine, Tzu Chi University, Hualien 970374, Taiwan
| | - Wen-Tien Wu
- Department of Orthopedics, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien 970473, Taiwan; (T.-C.Y.); (W.-T.W.); (I.-H.C.)
- Institute of Medical Sciences, Tzu Chi University, Hualien 970374, Taiwan;
- School of Medicine, Tzu Chi University, Hualien 970374, Taiwan
| | - Ru-Ping Lee
- Institute of Medical Sciences, Tzu Chi University, Hualien 970374, Taiwan;
| | - Ing-Ho Chen
- Department of Orthopedics, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien 970473, Taiwan; (T.-C.Y.); (W.-T.W.); (I.-H.C.)
- School of Medicine, Tzu Chi University, Hualien 970374, Taiwan
| | - Jen-Hung Wang
- Department of Medical Research, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien 970473, Taiwan;
| | - Shu-Hui Wen
- Institute of Medical Sciences, Tzu Chi University, Hualien 970374, Taiwan;
- Department of Public Health, Tzu Chi University, Hualien 970374, Taiwan
| | - Kuang-Ting Yeh
- Department of Orthopedics, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien 970473, Taiwan; (T.-C.Y.); (W.-T.W.); (I.-H.C.)
- Institute of Medical Sciences, Tzu Chi University, Hualien 970374, Taiwan;
- School of Medicine, Tzu Chi University, Hualien 970374, Taiwan
- Graduate Institute of Clinical Pharmacy, Tzu Chi University, Hualien 970374, Taiwan
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Han Z, Wang K, Ding S, Zhang M. Cross-talk of inflammation and cellular senescence: a new insight into the occurrence and progression of osteoarthritis. Bone Res 2024; 12:69. [PMID: 39627227 PMCID: PMC11615234 DOI: 10.1038/s41413-024-00375-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2024] [Revised: 09/10/2024] [Accepted: 09/24/2024] [Indexed: 12/06/2024] Open
Abstract
Osteoarthritis (OA) poses a significant challenge in orthopedics. Inflammatory pathways are regarded as central mechanisms in the onset and progression of OA. Growing evidence suggests that senescence acts as a mediator in inflammation-induced OA. Given the lack of effective treatments for OA, there is an urgent need for a clearer understanding of its pathogenesis. In this review, we systematically summarize the cross-talk between cellular senescence and inflammation in OA. We begin by focusing on the mechanisms and hallmarks of cellular senescence, summarizing evidence that supports the relationship between cellular senescence and inflammation. We then discuss the mechanisms of interaction between cellular senescence and inflammation, including senescence-associated secretory phenotypes (SASP) and the effects of pro- and anti-inflammatory interventions on cellular senescence. Additionally, we focus on various types of cellular senescence in OA, including senescence in cartilage, subchondral bone, synovium, infrapatellar fat pad, stem cells, and immune cells, elucidating their mechanisms and impacts on OA. Finally, we highlight the potential of therapies targeting senescent cells in OA as a strategy for promoting cartilage regeneration.
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Affiliation(s)
- Zeyu Han
- Department of Foot and Ankle Surgery, Beijing Tongren Hospital, Capital Medical University, 100730, Beijing, PR China
| | - Ketao Wang
- Department of Foot and Ankle Surgery, Beijing Tongren Hospital, Capital Medical University, 100730, Beijing, PR China
| | - Shenglong Ding
- Department of Foot and Ankle Surgery, Beijing Tongren Hospital, Capital Medical University, 100730, Beijing, PR China
| | - Mingzhu Zhang
- Department of Foot and Ankle Surgery, Beijing Tongren Hospital, Capital Medical University, 100730, Beijing, PR China.
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Du C, Liu J, Liu S, Xiao P, Chen Z, Chen H, Huang W, Lei Y. Bone and Joint-on-Chip Platforms: Construction Strategies and Applications. SMALL METHODS 2024; 8:e2400436. [PMID: 38763918 DOI: 10.1002/smtd.202400436] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/25/2024] [Revised: 04/28/2024] [Indexed: 05/21/2024]
Abstract
Organ-on-a-chip, also known as "tissue chip," is an advanced platform based on microfluidic systems for constructing miniature organ models in vitro. They can replicate the complex physiological and pathological responses of human organs. In recent years, the development of bone and joint-on-chip platforms aims to simulate the complex physiological and pathological processes occurring in human bones and joints, including cell-cell interactions, the interplay of various biochemical factors, the effects of mechanical stimuli, and the intricate connections between multiple organs. In the future, bone and joint-on-chip platforms will integrate the advantages of multiple disciplines, bringing more possibilities for exploring disease mechanisms, drug screening, and personalized medicine. This review explores the construction and application of Organ-on-a-chip technology in bone and joint disease research, proposes a modular construction concept, and discusses the new opportunities and future challenges in the construction and application of bone and joint-on-chip platforms.
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Affiliation(s)
- Chengcheng Du
- Department of Orthopedics, Orthopedic Laboratory of Chongqing Medical University, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China
| | - Jiacheng Liu
- Department of Orthopedics, Orthopedic Laboratory of Chongqing Medical University, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China
| | - Senrui Liu
- Department of Orthopedics, Orthopedic Laboratory of Chongqing Medical University, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China
| | - Pengcheng Xiao
- Department of Orthopedics, Orthopedic Laboratory of Chongqing Medical University, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China
| | - Zhuolin Chen
- Department of Orthopedics, Orthopedic Laboratory of Chongqing Medical University, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China
| | - Hong Chen
- Department of Orthopedics, Orthopedic Laboratory of Chongqing Medical University, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China
| | - Wei Huang
- Department of Orthopedics, Orthopedic Laboratory of Chongqing Medical University, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China
| | - Yiting Lei
- Department of Orthopedics, Orthopedic Laboratory of Chongqing Medical University, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China
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Ngowi EE, Lu T, Liu Q, Xie X, Wang N, Luo L, Deng L, Zhou Y, Zhang Z, Qiao A. Biofluid-Derived Exosomal LncRNAs: Their Potential in Obesity and Related Comorbidities. BIOLOGY 2024; 13:976. [PMID: 39765643 PMCID: PMC11673191 DOI: 10.3390/biology13120976] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/05/2024] [Revised: 11/21/2024] [Accepted: 11/24/2024] [Indexed: 01/03/2025]
Abstract
Obesity has escalated into a critical global health crisis, tripling in prevalence since the mid-1970s. This increase mirrors the rise in metabolic-associated diseases such as type 2 diabetes (T2D) and its complications, certain cancers, and cardiovascular conditions. While substantial research efforts have enriched our understanding and led to the development of innovative management strategies for these diseases, the suboptimal response rates of existing therapies remain a major obstacle to effectively managing obesity and its associated conditions. Over the years, inter-organ communication (IOC) has emerged as a crucial factor in the development and progression of metabolic disorders. Exosomes, which are nano-sized vesicular couriers released by cells, play a significant role in this communication by transporting proteins, lipids, and nucleic acids across cellular landscapes. The available evidence indicates that exosomal RNAs present in biofluids such as blood, urine, milk, vitreous humor (VH), and cerebrospinal fluid (CSF) are altered in numerous diseases, suggesting their diagnostic and therapeutic potential. Long non-coding RNAs contained in exosomes (exo-lncRNAs) have attracted considerable interest, owing to their ability to interact with critical components involved in a multitude of metabolic pathways. Recent studies have found that alterations in exo-lncRNAs in biofluids correlate with several metabolic parameters in patients with metabolic-associated conditions; however, their exact roles remain largely unclear. This review highlights the diagnostic and therapeutic potential of exosomal lncRNAs in obesity and its associated conditions, emphasizing their role in IOC and disease progression, aiming to pave the way for further research in this promising domain.
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Affiliation(s)
- Ebenezeri Erasto Ngowi
- Zhongshan Institute for Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Zhongshan 528400, China; (E.E.N.); (T.L.); (Q.L.); (X.X.); (N.W.); (L.L.); (L.D.) (Y.Z.); (Z.Z.)
- Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Shanghai 201203, China
- University of Chinese Academy of Sciences, Beijing 101408, China
| | - Tuyan Lu
- Zhongshan Institute for Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Zhongshan 528400, China; (E.E.N.); (T.L.); (Q.L.); (X.X.); (N.W.); (L.L.); (L.D.) (Y.Z.); (Z.Z.)
| | - Qing Liu
- Zhongshan Institute for Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Zhongshan 528400, China; (E.E.N.); (T.L.); (Q.L.); (X.X.); (N.W.); (L.L.); (L.D.) (Y.Z.); (Z.Z.)
| | - Xianghong Xie
- Zhongshan Institute for Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Zhongshan 528400, China; (E.E.N.); (T.L.); (Q.L.); (X.X.); (N.W.); (L.L.); (L.D.) (Y.Z.); (Z.Z.)
| | - Ning Wang
- Zhongshan Institute for Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Zhongshan 528400, China; (E.E.N.); (T.L.); (Q.L.); (X.X.); (N.W.); (L.L.); (L.D.) (Y.Z.); (Z.Z.)
| | - Liping Luo
- Zhongshan Institute for Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Zhongshan 528400, China; (E.E.N.); (T.L.); (Q.L.); (X.X.); (N.W.); (L.L.); (L.D.) (Y.Z.); (Z.Z.)
| | - Lijuan Deng
- Zhongshan Institute for Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Zhongshan 528400, China; (E.E.N.); (T.L.); (Q.L.); (X.X.); (N.W.); (L.L.); (L.D.) (Y.Z.); (Z.Z.)
| | - Yinghua Zhou
- Zhongshan Institute for Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Zhongshan 528400, China; (E.E.N.); (T.L.); (Q.L.); (X.X.); (N.W.); (L.L.); (L.D.) (Y.Z.); (Z.Z.)
| | - Zhihong Zhang
- Zhongshan Institute for Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Zhongshan 528400, China; (E.E.N.); (T.L.); (Q.L.); (X.X.); (N.W.); (L.L.); (L.D.) (Y.Z.); (Z.Z.)
| | - Aijun Qiao
- Zhongshan Institute for Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Zhongshan 528400, China; (E.E.N.); (T.L.); (Q.L.); (X.X.); (N.W.); (L.L.); (L.D.) (Y.Z.); (Z.Z.)
- Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Shanghai 201203, China
- University of Chinese Academy of Sciences, Beijing 101408, China
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Meng X, Li H, Liu X, Li B, Liu Y, Li M, Sun D, Yang Y, Gao Y, Pei J. Drinking brick tea containing high fluoride increases the prevalence of osteoarthritis in Tibetan, China. INTERNATIONAL JOURNAL OF ENVIRONMENTAL HEALTH RESEARCH 2024; 34:3760-3770. [PMID: 38445824 DOI: 10.1080/09603123.2024.2324936] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/17/2023] [Accepted: 02/26/2024] [Indexed: 03/07/2024]
Abstract
The prevalence of osteoarthritis (OA) in Tibetans is higher than that in Han, while Tibetans have a habit of drinking brick tea with high fluoride. A cross-sectional study was conducted to explore the association between fluoride exposure in drinking brick tea and OA. All subjects were divided into four groups by the quartiles (Q) of tea fluoride (TF) and urine fluoride (UF). ROC was plotted and OR were obtained using logistic regression model. The prevalence of OA in the Q3 and Q4 group of TF were 2.2 and 2.7 times higher than in the Q1 group, and the prevalence of OA in the Q2, Q3 and Q4 group of UF were 3.2, 3.5, and 4.1 times higher than in the Q1 group. ROC analysis showed the cutoff values were 4.523 mg/day (TF) and 1.666 mg/L (UF). In conclusion, excessive fluoride in drinking brick tea could be a risk factor for developing OA.
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Affiliation(s)
- Xinyue Meng
- Key Lab of Etiology and Epidemiology, Education Bureau of Heilongjiang Province & Ministry of Health (23618504), Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Heilongjiang Province, China
| | - Hanying Li
- Key Lab of Etiology and Epidemiology, Education Bureau of Heilongjiang Province & Ministry of Health (23618504), Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Heilongjiang Province, China
| | - Xiaona Liu
- Key Lab of Etiology and Epidemiology, Education Bureau of Heilongjiang Province & Ministry of Health (23618504), Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Heilongjiang Province, China
| | - Bingyun Li
- Key Lab of Etiology and Epidemiology, Education Bureau of Heilongjiang Province & Ministry of Health (23618504), Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Heilongjiang Province, China
| | - Yang Liu
- Key Lab of Etiology and Epidemiology, Education Bureau of Heilongjiang Province & Ministry of Health (23618504), Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Heilongjiang Province, China
| | - Mang Li
- Key Lab of Etiology and Epidemiology, Education Bureau of Heilongjiang Province & Ministry of Health (23618504), Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Heilongjiang Province, China
| | - Dianjun Sun
- Key Lab of Etiology and Epidemiology, Education Bureau of Heilongjiang Province & Ministry of Health (23618504), Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Heilongjiang Province, China
| | - Yanmei Yang
- Key Lab of Etiology and Epidemiology, Education Bureau of Heilongjiang Province & Ministry of Health (23618504), Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Heilongjiang Province, China
| | - Yanhui Gao
- Key Lab of Etiology and Epidemiology, Education Bureau of Heilongjiang Province & Ministry of Health (23618504), Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Heilongjiang Province, China
| | - Junrui Pei
- Key Lab of Etiology and Epidemiology, Education Bureau of Heilongjiang Province & Ministry of Health (23618504), Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Heilongjiang Province, China
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Li ZB, Li YZ, Sun ZP, Li WX, Xiao Z, Wang F. ZEB2 knockdown inhibits interleukin-1β-induced cartilage degradation and inflammatory response through the Wnt/β-catenin pathway in human chondrocytes. Scand J Rheumatol 2024; 53:409-419. [PMID: 38899454 DOI: 10.1080/03009742.2024.2358594] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2024] [Accepted: 05/20/2024] [Indexed: 06/21/2024]
Abstract
OBJECTIVE Osteoarthritis (OA) is a degenerative disease of the joints characterized by inflammation and cartilage degeneration. Zinc finger E-box binding homeobox 2 (ZEB2) contains various function domains that interact with multiple transcription factors involved in various cellular functions. However, the function of ZEB2 in OA has not been clearly illustrated. METHOD Interleukin-1β (IL-1β) was used to establish an OA model in vitro. We quantified the ZEB2 expression in cartilage tissues from OA patients and IL-1β-induced chondrocytes through reverse transcription-quantitative polymerase chain reaction and Western blot. We then used functional assays to explore the function of ZEB2 during OA progression. RESULTS ZEB2 expression was increased in OA cartilage tissues and chondrocytes. The silencing of ZEB2 increased aggrecan and collagen II levels, and reduced the content of matrix metalloproteinase-3 (MMP-3), MMP-9, and MMP-13. ZEB2 knockdown inhibited the effects of IL-1β on the production of nitric oxide and prostaglandin E2, and the expression of inducible nitric oxide synthase and cyclooxygenase-2. ZEB2 inhibition also suppressed the levels of IL-6 and tumour necrosis factor-α, and increased the IL-10 level in IL-1β-treated cells. Mechanically, ZEB2 knockdown blocked the activation of the Wnt/β-catenin pathway in chondrocytes. CONCLUSION Knockdown of ZEB2 alleviated IL-1β-induced cartilage degradation and the inflammatory response through the Wnt/β-catenin pathway in chondrocytes.
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Affiliation(s)
- Z B Li
- Trauma Ward 2, The Affiliated Hospital of Shaanxi University of Chinese Medicine, Xianyang, Shaanxi, PR China
| | - Y Z Li
- Department of Orthopedics, Shangluo Chinese Medicine Hospital, Shangluo, Shaanxi, PR China
| | - Z P Sun
- Trauma Ward 2, The Affiliated Hospital of Shaanxi University of Chinese Medicine, Xianyang, Shaanxi, PR China
| | - W X Li
- Trauma Ward 2, The Affiliated Hospital of Shaanxi University of Chinese Medicine, Xianyang, Shaanxi, PR China
| | - Z Xiao
- Trauma Ward 2, The Affiliated Hospital of Shaanxi University of Chinese Medicine, Xianyang, Shaanxi, PR China
| | - F Wang
- Trauma Ward 2, The Affiliated Hospital of Shaanxi University of Chinese Medicine, Xianyang, Shaanxi, PR China
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Jiang P, Zhou X, Yang Y, Bai L. Pectolinarigenin targeting FGFR3 alleviates osteoarthritis progression by regulating the NF-κB/NLRP3 inflammasome pyroptotic pathway. Int Immunopharmacol 2024; 140:112741. [PMID: 39094365 DOI: 10.1016/j.intimp.2024.112741] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2024] [Revised: 07/08/2024] [Accepted: 07/19/2024] [Indexed: 08/04/2024]
Abstract
OBJECTIVE Osteoarthritis (OA) is a chronic degenerative disease characterized by cartilage degeneration, involving inflammation, pyroptosis, and degeneration of the extracellular matrix (ECM). Pectolinarigenin (PEC) is a natural flavonoid with antioxidant, anti-inflammatory and anti-tumor properties. This study aims to explore the potential of PEC in ameliorating OA progression and its underlying mechanisms. METHODS Chondrocytes were exposed to 10 ng/mL IL-1β to simulate OA-like changes. The effect of PEC on IL-1β-treated chondrocytes was assessed using ELISA, western blot, and immunofluorescence. The mRNA sequencing (mRNA-seq) was employed to explore the possible targets of PEC in delaying OA progression. The OA mouse model was induced through anterior cruciate ligament transection (ACLT) and divided into sham, ACLT, ACLT+5 mg/kg PEC, and ACLT+10 mg/kg PEC groups. Micro-computed tomography and histological analysis were conducted to confirm the beneficial effects of PEC on OA in vivo. RESULTS PEC mitigated chondrocyte pyroptosis, as evidenced by reduced levels of pyroptosis-related proteins. Additionally, PEC attenuated IL-1β-mediated chondrocyte ECM degradation and inflammation. Mechanistically, mRNA-seq showed that FGFR3 was a downstream target of PEC. FGFR3 silencing reversed the beneficial effects of PEC on IL-1β-exposed chondrocytes. PEC exerted anti-pyroptotic, anti-ECM degradative, and anti-inflammatory effects through upregulating FGFR3 to inhibit the NF-κB/NLRP3 pyroptosis-related pathway. Consistently, in vivo experiments demonstrated the chondroprotective effects of PEC in OA mice. CONCLUSION PEC alleviate OA progression by FGFR3/NF-κB/NLRP3 pathway mediated chondrocyte pyroptosis, ECM degradation and inflammation, suggesting the potential of PEC as a therapeutic agent for OA.
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Affiliation(s)
- Peng Jiang
- Department of Orthopedics, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China
| | - Xiaonan Zhou
- Department of Orthopedics, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China
| | - Yue Yang
- Department of Orthopedics, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China
| | - Lunhao Bai
- Department of Orthopedics, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China.
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Sheinkop M, Langhenry M, Abd-Elsayed A. The Outcomes at 3 Years in 82 Knees with Kellgren and Lawrence 2-3 Osteoarthritis Treated with an Autologous Protein Fluid Concentrate Produced with a Fluid Volume Reducer. Life (Basel) 2024; 14:1340. [PMID: 39459640 PMCID: PMC11509826 DOI: 10.3390/life14101340] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2024] [Revised: 10/15/2024] [Accepted: 10/18/2024] [Indexed: 10/28/2024] Open
Abstract
INTRODUCTION Knee osteoarthritis (OA) is a highly prevalent and debilitating condition with significant emotional and economic impacts. Current treatment options may only provide temporary pain relief and are not regenerative, thus the progression of knee OA is not deterred and total knee arthroplasty is inevitable. Injection therapies with orthobiologics possess regenerative potential and are an emerging treatment option. We present a prospective study aimed at examining patients with knee OA who had received an autologous platelet concentrate fluid (APCF) injection produced through a fluid volume reducer. METHODS This was an observational review of the results following an APCF injection in a cohort of patients at a single site. Patients were included in the study if they were diagnosed with K/L grade 2-3 knee OA and treated with an APCF knee injection. Patients were excluded if they had obtained an orthobiologic injection in the three months prior to study enrollment or if baseline data were unavailable. Knee score and function score were used to assess patients at the baseline and post-injection follow-ups. RESULTS Improvements for knee score were statistically significant for the follow-ups at three months, six months, one year, and three years. Function score improved, with statistically significant changes for the three month and three year follow-ups. CONCLUSIONS Our study demonstrates that there is some utility in using APCF injection for knee OA, with improvements that may be sustained up to three years in some patients.
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Affiliation(s)
| | - Mary Langhenry
- Cellular Orthopedics, Chicago, IL 60661, USA; (M.S.); (M.L.)
| | - Alaa Abd-Elsayed
- Department of Anesthesiology, University of Wisconsin, Madison, WI 53706, USA
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He Z, Gong Z, Jiao S, Xiong W, Hao X, Cui J, Zhang J. Genetic predisposition to thyrotoxicosis and onset of knee osteoarthritis. Front Endocrinol (Lausanne) 2024; 15:1364027. [PMID: 39415792 PMCID: PMC11479908 DOI: 10.3389/fendo.2024.1364027] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/01/2024] [Accepted: 08/16/2024] [Indexed: 10/19/2024] Open
Abstract
OBJECTIVE Thyroid hormones have actions on cartilage, whereas the association between thyroid hormone related diseases and osteoarthritis (OA) are unclear. This study aims to investigate the association between thyrotoxicosis and OA. METHODS Summary-level genetic data of thyrotoxicosis were obtained from FinnGen cohorts (nCase = 10,569, nControl = 762,037). Summary-level data of OA were obtained from a large-scale genome-wide association study of UK Biobank (nCase = 40,659, nControl = 756,338). Single nucleotide polymorphisms (SNPs) robustly associated with thyrotoxicosis or OA were used as genetic instruments. A two-sample bidirectional Mendelian randomization (MR) analysis was designed to assess the effect of genetic predisposition of thyrotoxicosis on OA risk, as well as the reverse their relationship. The causal effect was estimated by Inverse-variance weighted method, with weighted median and MR-Egger as supplementary methods. RESULTS Genetic predisposition of thyrotoxicosis was associated with the onset of knee OA (autoimmune hyperthyroidism: odds ratio [OR]: 1.05, 95% confidence interval [CI]: 1.03-1.07, FDR < 0.001; thyrotoxicosis: OR: 1.05, 95% CI: 1.02-1.08, FDR = 0.016; thyrotoxicosis with diffuse goitre: OR: 1.04, 95% CI: 1.02-1.07, FDR = 0.003; other and/or unspecified thyrotoxicosis: OR: 1.05, 95% CI: 1.02-1.09, FDR = 0.003), whereas thyrotoxicosis was not associated with hip OA. In reverse MR analysis, genetic predisposition to OA was not associated with thyrotoxicosis. No pleiotropy was identified in the MR analyses. Sensitivity analyses indicated the robustness of the MR estimates. CONCLUSION This study provides MR evidence supporting causal association of thyrotoxicosis with knee OA in European population, whereas OA may have no causal effects on thyrotoxicosis.
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Affiliation(s)
- Zhiyi He
- Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Zailing Gong
- Clinical Innovation and Research Center (CIRC), Shenzhen Hospital, Southern Medical University, Shenzhen, China
| | - Sizhe Jiao
- The First Clinical Medical College, Southern Medical University, Guangzhou, China
| | - Wei Xiong
- Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xiaoxia Hao
- Department of Rehabilitation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Jiarui Cui
- Clinical Innovation and Research Center (CIRC), Shenzhen Hospital, Southern Medical University, Shenzhen, China
| | - Jiaming Zhang
- Clinical Innovation and Research Center (CIRC), Shenzhen Hospital, Southern Medical University, Shenzhen, China
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Ciaffi J, Papalexis N, Vanni E, Miceli M, Faldini C, Scotti L, Zambon A, Salvarani C, Caporali R, Facchini G, Ursini F. Minimally invasive interventional procedures for osteoarthritis and inflammatory arthritis: A systematic review and meta-analysis. Semin Arthritis Rheum 2024; 68:152525. [PMID: 39137511 DOI: 10.1016/j.semarthrit.2024.152525] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2024] [Revised: 07/12/2024] [Accepted: 07/22/2024] [Indexed: 08/15/2024]
Abstract
OBJECTIVE to summarize the evidence on the efficacy of minimally invasive interventional procedures such as radiofrequency ablation (RFA) and transcatheter arterial embolization (TAE) in patients with osteoarthritis or inflammatory arthritis. METHODS a literature search was conducted in PubMed and Web of Science databases. Both randomized controlled trials (RCTs) and non-randomized studies of interventions (NRSI) were included. The results were organized according to the treated anatomical site: knee, hip, foot and ankle, shoulder, hand and wrist, sacroiliac joints. Data about treatment efficacy were extracted. The main outcome was change in pain intensity using the 0-10 visual analog scale (VAS) from baseline to 1 month. Additional timepoints at 3, 6 and 12 months were assessed. Change in functional status was evaluated. Pooled estimates were calculated as the mean difference (MD) and 95 % confidence interval relative to baseline. The meta-analyses of RCTs and NRSI were conducted separately. RESULTS of the 4599 retrieved articles, 164 were included in the review and, considering all the established timepoints, 111 (38 RCTs and 73 NRSI) were selected for the meta-analysis. Only one article described patients with inflammatory arthritis. In the meta-analysis of RCTs, one month after the procedure, MD in VAS was -3.98 (-4.41 to -3.55; k = 21) for knee RFA, and -3.18 (-3.96 to -2.39; k = 8) for sacroiliac joints RFA. In the meta-analysis of NRSI, MD in VAS was -4.12 (-4.63 to -3.61; k = 23) for knee RFA, -3.84 (-4.77 to -2.92; k = 7) for knee TAE, -4.34 (-4.96 to -3.71; k = 2) for hip RFA, -3.83 (-4.52 to -3.15; k = 3) for shoulder RFA and -4.93 (-5.58 to -4.28; k = 14) for sacroiliac joints RFA. Significant decrease in pain intensity was found also at 3, 6 and 12 months. Additionally, functional status improved at all the assessed timepoints. CONCLUSION minimally invasive interventional procedures can improve pain and functional status of patients affected by OA or chronic sacroiliac pain of degenerative origin. Further research is warranted in the field of inflammatory rheumatic diseases.
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Affiliation(s)
- Jacopo Ciaffi
- Medicine & Rheumatology Unit, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy; Department of Biomedical and Neuromotor Sciences (DIBINEM), University of Bologna, Bologna, Italy.
| | - Nicolas Papalexis
- Diagnostic and Interventional Radiology Unit, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy
| | - Elena Vanni
- Division of Rheumatology, Azienda USL-IRCCS di Reggio Emilia, Reggio Emilia and Università di Modena e Reggio Emilia, Modena, Italy
| | - Marco Miceli
- Diagnostic and Interventional Radiology Unit, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy
| | - Cesare Faldini
- Department of Biomedical and Neuromotor Sciences (DIBINEM), University of Bologna, Bologna, Italy; 1st Orthopaedic and Traumatologic Clinic, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy
| | - Lorenza Scotti
- Department of Translational Medicine, Università del Piemonte Orientale UPO, Novara, Italy
| | - Antonella Zambon
- Department of Statistics and Quantitative Methods, University of Milano-Bicocca, Milan, Italy; Biostatistics Unit, IRCCS Istituto Auxologico Italiano, Milan, Italy
| | - Carlo Salvarani
- Division of Rheumatology, Azienda USL-IRCCS di Reggio Emilia, Reggio Emilia and Università di Modena e Reggio Emilia, Modena, Italy
| | - Roberto Caporali
- Department of Clinical Sciences and Community Health, University of Milan and ASST G. Pini-CTO, Milan, Italy
| | - Giancarlo Facchini
- Diagnostic and Interventional Radiology Unit, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy
| | - Francesco Ursini
- Medicine & Rheumatology Unit, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy; Department of Biomedical and Neuromotor Sciences (DIBINEM), University of Bologna, Bologna, Italy
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Docking S, Ademi Z, Barton C, Wallis JA, Harris IA, de Steiger R, Buchbinder R, Brusco N, Young K, Pazzinatto MF, Harries D, Vertullo CJ, Ackerman IN. Lifetime Cost-Effectiveness of Structured Education and Exercise Therapy for Knee Osteoarthritis in Australia. JAMA Netw Open 2024; 7:e2436715. [PMID: 39352701 PMCID: PMC11445685 DOI: 10.1001/jamanetworkopen.2024.36715] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/04/2024] Open
Abstract
Importance Structured education and exercise therapy programs have been proposed to reduce reliance on total knee replacement (TKR) surgery and improve health care sustainability. The long-term cost-effectiveness of these programs is unclear. Objectives To estimate the lifetime cost-effectiveness of implementing a national structured education and exercise therapy program for individuals with knee osteoarthritis with the option for future TKR compared with usual care (TKR for all). Design, Setting, and Participants This economic evaluation used a life table model in combination with a Markov model to compare costs and health outcomes of a national education and exercise therapy program vs usual care in the Australian health care system. Subgroup, deterministic, and probabilistic sensitivity analyses were completed. A hypothetical cohort of adults aged 45 to 84 years who would undergo TKR was created. Exposure Structured education and exercise therapy intervention provided by physiotherapists. The comparator was usual care where all people undergo TKR without accessing the program in the first year. Main Outcomes and Measures Incremental net monetary benefit (INMB), with an incremental cost-effectiveness ratio threshold of 28 033 Australian dollars (A$) per quality-adjusted life-year (QALY) gained, was calculated from a health care perspective. Transition probabilities, costs, and utilities were estimated from national registries and a randomized clinical trial. Results The hypothetical cohort included 61 394 individuals (53.9% female; 93.6% aged ≥55 years). Implementation of an education and exercise therapy program resulted in a lifetime cost savings of A$498 307 942 (US $339 922 227), or A$7970 (US $5537) per individual, and resulted in fewer QALYs (0.43 per individual) compared with usual care. At a population level, education and exercise therapy was not cost-effective at the lifetime horizon (INMB, -A$4090 [-US $2841]). Subgroup analysis revealed that the intervention was cost-effective only for the first 9 years and over a lifetime only in individuals with no or mild pain at baseline (INMB, A$11 [US $8]). Results were robust to uncertainty around model inputs. Conclusions and Relevance In this economic evaluation of structured education and exercise therapy compared with usual care, the intervention was not cost-effective over the lifetime for all patients but was for the first 9 years and for those with minimal pain. These findings point to opportunities to invest early cost savings in additional care or prevention, including targeted implementation to specific subgroups.
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Affiliation(s)
- Sean Docking
- School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia
| | - Zanfina Ademi
- Centre for Medicine Use and Safety, Monash University, Melbourne, Australia
| | - Christian Barton
- La Trobe Sport and Exercise Medicine Research Centre, La Trobe University, Melbourne, Australia
| | - Jason A Wallis
- School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia
- Cabrini Health, Malvern, Australia
| | - Ian A Harris
- South West Sydney Campus, School of Clinical Medicine, UNSW Medicine and Health, UNSW Sydney, Liverpool, Australia
| | - Richard de Steiger
- Department of Surgery Epworth Healthcare, The University of Melbourne, Melbourne, Australia
| | - Rachelle Buchbinder
- School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia
| | - Natasha Brusco
- School of Primary and Allied Health Care, Monash University, Melbourne, Australia
| | | | | | - Dylan Harries
- South Australian Health and Medical Research Institute, Adelaide, Australia
| | - Christopher J Vertullo
- Australian Orthopaedic Association National Joint Replacement Registry, Adelaide, Australia
- Menzies Health Institute, Griffith University, Southport, Australia
| | - Ilana N Ackerman
- School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia
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Wu YL, Luo Y, Yang JM, Wu YQ, Zhu Q, Li Y, Hu H, Zhang JH, Zhong YB, Wang MY. Effects of transcranial direct current stimulation on pain and physical function in patients with knee osteoarthritis: a systematic review and meta-analysis. BMC Musculoskelet Disord 2024; 25:703. [PMID: 39227806 PMCID: PMC11370230 DOI: 10.1186/s12891-024-07805-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2024] [Accepted: 08/21/2024] [Indexed: 09/05/2024] Open
Abstract
BACKGROUND Keen Osteoarthritis (KOA) is a common chronic disabling disease characterized by joint pain and dysfunction, which seriously affects patients' quality of life. Recent studies have shown that transcranial direct current stimulation (tDCS) was a promising treatment for KOA. PURPOSE Investigate the effects of tDCS on pain and physical function in patients with KOA. METHODS Randomized controlled trials related to tDCS and KOA were systematically searched in the PubMed, Embase, Medline, Cochrane Library, CINHL, and Web of Science databases from inception to July 23, 2024. The pain intensity was evaluated using the visual analog scale or the numeric rating scale, and the pain sensitivity was assessed using conditioned pain modulation, pressure pain threshold, heat pain threshold, or heat pain tolerance. The physical function outcome was evaluated using the Western Ontario and McMaster Universities Osteoarthritis Index or the Knee injury and Osteoarthritis Outcome Score. Statistical analysis was performed using Review Manager 5.4. RESULTS Seven studies with a total of 503 participants were included. Compared to sham tDCS, tDCS was effective in reducing the short-term pain intensity (SMD: -0.58; 95% CI: -1.02, -0.14; p = 0.01) and pain sensitivity (SMD: -0.43; 95% CI: -0.70, -0.16; p = 0.002) but failed to significantly improve the long-term pain intensity (SMD: -0.26; 95% CI: -0.59, 0.08; p = 0.13) in KOA patients. In addition, tDCS did not significantly improve the short-term (SMD: -0.13; 95% CI: -0.35, 0.08; p = 0.22) and long-term (SMD: 0.02; 95% CI: -0.22, 0.25; p = 0.90) physical function in patients with KOA. CONCLUSIONS The tDCS can reduce short-term pain intensity and sensitivity but fails to significantly relieve long-term pain intensity and improve the physical function in patients with KOA. Thus, tDCS may be a potential therapeutic tool to reduce short-term pain intensity and pain sensitivity in patients with KOA.
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Affiliation(s)
- Yan-Lin Wu
- Gannan Medical University, Ganzhou City, Jiangxi Province, 341000, China
- Department of Rehabilitation Medicine, First Affiliated Hospital of Gannan Medical University, Ganzhou City, Jiangxi Province, 341000, China
| | - Yun Luo
- Department of Rehabilitation Medicine, First Affiliated Hospital of Gannan Medical University, Ganzhou City, Jiangxi Province, 341000, China
| | - Jia-Ming Yang
- Gannan Medical University, Ganzhou City, Jiangxi Province, 341000, China
- Department of Rehabilitation Medicine, First Affiliated Hospital of Gannan Medical University, Ganzhou City, Jiangxi Province, 341000, China
| | - Yong-Qiang Wu
- Gannan Medical University, Ganzhou City, Jiangxi Province, 341000, China
- Department of Rehabilitation Medicine, First Affiliated Hospital of Gannan Medical University, Ganzhou City, Jiangxi Province, 341000, China
| | - Qiang Zhu
- Department of Rehabilitation Medicine, First Affiliated Hospital of Gannan Medical University, Ganzhou City, Jiangxi Province, 341000, China
| | - Yi Li
- Department of Rehabilitation Medicine, First Affiliated Hospital of Gannan Medical University, Ganzhou City, Jiangxi Province, 341000, China
| | - Hao Hu
- Gannan Medical University, Ganzhou City, Jiangxi Province, 341000, China
- Department of Rehabilitation Medicine, First Affiliated Hospital of Gannan Medical University, Ganzhou City, Jiangxi Province, 341000, China
| | - Jia-Hong Zhang
- Department of Rehabilitation Medicine, First Affiliated Hospital of Gannan Medical University, Ganzhou City, Jiangxi Province, 341000, China
| | - Yan-Biao Zhong
- Department of Rehabilitation Medicine, First Affiliated Hospital of Gannan Medical University, Ganzhou City, Jiangxi Province, 341000, China
| | - Mao-Yuan Wang
- Department of Rehabilitation Medicine, First Affiliated Hospital of Gannan Medical University, Ganzhou City, Jiangxi Province, 341000, China.
- Ganzhou Key Laboratory of Rehabilitation Medicine, First Affiliated Hospital of Gannan Medical University, Ganzhou City, Jiangxi Province, 341000, China.
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Jansen NEJ, Schiphof D, Runhaar J, Oei EHG, Bierma-Zeinstra SMA, Middelkoop MV. Planned or recent first consultation with the general practitioner for knee complaints: Is it indicative of early-stage knee osteoarthritis? OSTEOARTHRITIS AND CARTILAGE OPEN 2024; 6:100493. [PMID: 38966077 PMCID: PMC11223112 DOI: 10.1016/j.ocarto.2024.100493] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2024] [Accepted: 06/03/2024] [Indexed: 07/06/2024] Open
Abstract
Objective No established definition for early-stage knee osteoarthritis (KOA) is available, nor classification criteria. Identifying the characteristics of individuals presenting with early-stage KOA symptoms can enhance diagnosis to prevent progression. This study aimed to describe clinical and structural features of individuals presenting with knee complaints within two years after their first consultation, while exploring differences in the duration of knee complaints. Method Baseline data was used from the LITE randomized controlled trial, assessing the effectiveness of a lifestyle intervention for individuals with knee complaints and overweight in primary care. Baseline assessments included questionnaires, clinical assessment, and MRI of the most symptomatic knee. Differences between groups with varying durations of knee complaints (<12, ≥12-<24, ≥24 months) were evaluated. Results Participants (N = 218, 65% female, mean age 59 ± 6 years, mean BMI 32 ± 5 kg/m2) had a median knee complaint duration of 14 months, with an average KOOS pain score of 60 ± 17.46% reported their symptoms as unacceptable. Structural MRI-defined KOA was observed in 71% of participants. There were no significant differences in clinical or structural MRI features between different durations of knee complaints. Conclusion Within 24 months of initial consultation, over two-thirds of participants displayed MRI-defined structural KOA, and nearly half reported unacceptable symptom states. This study found no association between the duration of knee complaints and symptoms severity or structural KOA presence, underscoring the complexity of identifying stages of KOA among individuals with overweight. Future studies should explore additional features beyond current considerations to facilitate early-stage KOA diagnosis, specifically for individuals with overweight.
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Affiliation(s)
- Nuria EJ. Jansen
- Department of General Practice, Erasmus MC University Medical Center Rotterdam, the Netherlands
| | - Dieuwke Schiphof
- Department of General Practice, Erasmus MC University Medical Center Rotterdam, the Netherlands
| | - Jos Runhaar
- Department of General Practice, Erasmus MC University Medical Center Rotterdam, the Netherlands
| | - Edwin HG. Oei
- Department of Radiology & Nuclear Medicine, Erasmus MC University Medical Center Rotterdam, the Netherlands
| | | | - Marienke van Middelkoop
- Department of General Practice, Erasmus MC University Medical Center Rotterdam, the Netherlands
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41
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Mononen ME, Liukkonen MK, Turunen MJ. X-ray with finite element analysis is a viable alternative for MRI to predict knee osteoarthritis: Data from the Osteoarthritis Initiative. J Orthop Res 2024; 42:1964-1973. [PMID: 38650428 DOI: 10.1002/jor.25861] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/21/2023] [Revised: 02/29/2024] [Accepted: 04/03/2024] [Indexed: 04/25/2024]
Abstract
Magnetic resonance imaging (MRI) offers superior soft tissue contrast compared to clinical X-ray imaging methods, while also providing accurate three-dimensional (3D) geometries, it could be reasoned to be the best imaging modality to create 3D finite element (FE) geometries of the knee joint. However, MRI may not necessarily be superior for making tissue-level FE simulations of internal stress distributions within knee joint, which can be utilized to calculate subject-specific risk for the onset and development of knee osteoarthritis (KOA). Specifically, MRI does not provide any information about tissue stiffness, as the imaging is usually performed with the patient lying on their back. In contrast, native X-rays taken while the patient is standing indirectly reveal information of the overall health of the knee that is not seen in MRI. To determine the feasibility of X-ray workflow to generate FE models based on the baseline information (clinical image data and subject characteristics), we compared MRI and X-ray-based simulations of volumetric cartilage degenerations (N = 1213) against 8-year follow-up data. The results suggest that X-ray-based predictions of KOA are at least as good as MRI-based predictions for subjects with no previous knee injuries. This finding may have important implications for preventive care, as X-ray imaging is much more accessible than MRI.
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Affiliation(s)
- Mika E Mononen
- Department of Technical Physics, University of Eastern Finland, Kuopio, Finland
| | - Mimmi K Liukkonen
- Department of Clinical Radiology, Kuopio University Hospital, The Wellbeing Services County of North Savo, Kuopio, Finland
| | - Mikael J Turunen
- Department of Technical Physics, University of Eastern Finland, Kuopio, Finland
- Science Service Center, Kuopio University Hospital, The Wellbeing Services County of North Savo, Kuopio, Finland
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An J, Cheon SJ, Lee BH. The Effect of Combined Balance Exercise on Knee Range of Motion, Balance, Gait, and Functional Outcomes in Acute Phase Following Total Knee Arthroplasty: A Single-Blind Randomized Controlled Trial. MEDICINA (KAUNAS, LITHUANIA) 2024; 60:1389. [PMID: 39336430 PMCID: PMC11433847 DOI: 10.3390/medicina60091389] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/29/2024] [Revised: 08/19/2024] [Accepted: 08/21/2024] [Indexed: 09/30/2024]
Abstract
Background and Objectives: Total knee arthroplasty (TKA) improves balance performance in patients with osteoarthritis; however, balance deficit and fall incidence after TKA have been reported. This study aimed to determine the effects of combined balance exercises on knee range of motion (ROM), balance, gait, and functional outcomes during the acute phase after TKA. Materials and Methods: A total of 42 participants were randomly assigned to either the combined balance group (n = 21) or the general physical therapy (control) group (n = 21). The combined balance exercise group performed exercise programs for 30 min per session, five times a week for 4 weeks (20 sessions), and the control group completed general physical therapy, which included active simple exercise. Measurements were performed before and after the 4 weeks of training to assess changes in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), knee joint ROM, static balance, timed up-and-go (TUG), and 10 m walk test (10 MWT). Results: The combined balance exercise group demonstrated significant improvements post intervention (p < 0.05) for all outcomes. The time × group interaction effect for the WOMAC scores showed statistically significant interaction effects for pain, stiffness, and physical function; the static and dynamic balance values showed statistically significant interaction effects for CEA, PL, AV, and TUG; and gait ability showed a significant interaction effect for the 10 m walk test (p < 0.05). Conclusions: This study confirmed that combined balance training with general physical therapy has a positive effect on ROM, static and dynamic balance, gait, and functional outcomes in the acute phase post TKA and that combined balance exercise can be proposed as a rapid rehabilitation intervention with general physical therapy following TKA.
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Affiliation(s)
- Jungae An
- Graduate School of Physical Therapy, Sahmyook University, Seoul 01795, Republic of Korea
| | - Seong-Jin Cheon
- Graduate School of Physical Therapy, Sahmyook University, Seoul 01795, Republic of Korea
| | - Byoung-Hee Lee
- Department of Physical Therapy, Sahmyook University, Seoul 01795, Republic of Korea
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Yoshioka T, Arai N, Sugaya H, Taniguchi Y, Kanamori A, Gosho M, Okuno K, Kikuchi N, Hyodo K, Aoto K, Yamazaki M. The Effectiveness of Leukocyte-Poor Platelet-Rich Plasma Injections for Symptomatic Mild to Moderate Osteoarthritis of the Knee With Joint Effusion or Bone Marrow Lesions in a Japanese Population: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial. Am J Sports Med 2024; 52:2493-2502. [PMID: 39097760 DOI: 10.1177/03635465241263073] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 08/05/2024]
Abstract
BACKGROUND Intra-articular platelet-rich plasma (PRP) injections have been proposed for the treatment of knee osteoarthritis (OA); however, their effectiveness in Japanese patients remains unclear. PURPOSE To investigate whether 3 intra-articular injections of leukocyte-poor PRP (LP-PRP) improve symptoms and joint function in symptomatic Japanese patients with mild to moderate knee OA. STUDY DESIGN Randomized controlled trial; Level of evidence, 1. METHODS Of 72 patients screened, 30 were included and randomized to receive LP-PRP (n = 15) or saline (placebo; n = 15) injections between March 2019 and February 2023. Patients attended a screening visit and 3 treatment visits at 1 week apart, followed by 3 follow-up visits (at 4, 12, and 24 weeks) after the initial treatment visit. The primary efficacy outcome measure was the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, whereas the secondary efficacy outcome measures were the proportion of patients showing a visual analog scale (VAS) improvement of ≥50%. Magnetic resonance imaging was performed to evaluate joint effusion and bone marrow lesions using the Whole-Organ Magnetic Resonance Imaging Score. Patients were followed for 24 weeks. RESULTS Patients in the PRP group (mean age, 65.9 years) had a mean hip-knee-ankle angle of 5.1°, with 7 and 8 patients demonstrating Kellgren-Lawrence grade 2 and 3 knee OA, respectively. Patients in the placebo group (mean age, 67.9 years) had a mean hip-knee-ankle angle of 3.8°, with 6 and 9 patients showing Kellgren-Lawrence grade 2 and 3 knee OA, respectively. No significant differences were identified in any baseline factors. The percentage change in Western Ontario and McMaster Universities Osteoarthritis Index scores from baseline to 24 weeks was significantly different (P= .032) between the PRP (median, 75.9%; quantile 1 [Q1], 49.6; quantile 3 [Q3], 94.1]) and placebo (median, 27.7%; Q1, -9.4; Q3, 80.9]) groups. Overall, 73.3% and 28.6% of the PRP group and placebo group, respectively, exhibited an improvement in visual analog scale scores of ≥50%, with a significant improvement observed in the PRP group (P = .027). Changes in bone marrow lesions from baseline to 24 weeks, as assessed on magnetic resonance imaging, significantly differed between groups (P = .017), with no significant differences in other secondary endpoints. CONCLUSION In Japanese patients with knee OA, 3 intra-articular LP-PRP injections led to clinical improvements at 24-week follow-up and significant functional improvements and pain relief after 24 weeks.
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Affiliation(s)
- Tomokazu Yoshioka
- Division of Regenerative Medicine, Institute of Medicine, University of Tsukuba, Tsukuba, Japan
| | - Norihito Arai
- Department of Orthopedic Surgery, Institute of Medicine, University of Tsukuba, Tsukuba, Japan
| | - Hisashi Sugaya
- Department of Orthopedic Surgery, Institute of Medicine, University of Tsukuba, Tsukuba, Japan
| | - Yu Taniguchi
- Department of Orthopedic Surgery, Institute of Medicine, University of Tsukuba, Tsukuba, Japan
| | - Akihiro Kanamori
- Department of Orthopedic Surgery, Institute of Medicine, University of Tsukuba, Tsukuba, Japan
| | - Masahiko Gosho
- Department of Biostatistics, Institute of Medicine, University of Tsukuba, Tsukuba, Japan
| | - Kosuke Okuno
- Department of Orthopedic Surgery, Institute of Medicine, University of Tsukuba, Tsukuba, Japan
| | - Naoya Kikuchi
- Department of Orthopedic Surgery, Institute of Medicine, University of Tsukuba, Tsukuba, Japan
| | - Kojiro Hyodo
- Department of Orthopedic Surgery, Institute of Medicine, University of Tsukuba, Tsukuba, Japan
| | - Katsuya Aoto
- Department of Orthopedic Surgery, Institute of Medicine, University of Tsukuba, Tsukuba, Japan
| | - Masashi Yamazaki
- Department of Orthopedic Surgery, Institute of Medicine, University of Tsukuba, Tsukuba, Japan
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Tu B, Zhu Z, Lu P, Fang R, Peng C, Tong J, Ning R. Proteomic and lipidomic landscape of the infrapatellar fat pad and its clinical significance in knee osteoarthritis. Biochim Biophys Acta Mol Cell Biol Lipids 2024; 1869:159513. [PMID: 38788831 DOI: 10.1016/j.bbalip.2024.159513] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2023] [Revised: 04/25/2024] [Accepted: 05/20/2024] [Indexed: 05/26/2024]
Abstract
Osteoarthritis (OA) is a prevalent joint disease that can be exacerbated by lipid metabolism disorders. The intra-articular fat pad (IFP) has emerged as an active participant in the pathological changes of knee OA (KOA). However, the proteomic and lipidomic differences between IFP tissues from KOA and control individuals remain unclear. Samples of IFP were collected from individuals with and without OA (n = 6, n = 6). Subsequently, these samples underwent liquid chromatography/mass spectrometry-based label-free quantitative proteomic and lipidomic analysis to identify differentially expressed proteins (DEPs) and lipid metabolites (DELMs). The DEPs were further subjected to enrichment analysis, and hub DEPs were identified using multiple algorithms. Additionally, an OA diagnostic model was constructed based on the identified hub DEPs or DELMs. Furthermore, CIBERSORT was utilized to investigate the correlation between hub protein expression and immune-related modules in IFP of OA. Our results revealed the presence of 315 DEPs and eight DELMs in IFP of OA patients compared to the control group. Enrichment analysis of DEPs highlighted potential alterations in pathways related to coagulation, complement, fatty acid metabolism, and adipogenesis. The diagnostic model incorporating four hub DEPs (AUC = 0.861) or eight DELMs (AUC = 0.917) exhibited excellent clinical validity for diagnosing OA. Furthermore, the hub DEPs were found to be associated with immune dysfunction in IFP of OA. This study presents a distinct proteomic and lipidomic landscape of IFP between individuals with OA and those without. These findings provide valuable insights into the molecular changes associated with potential mechanisms underlying OA.
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Affiliation(s)
- Bizhi Tu
- Department of Orthopedics, The Third Affiliated Hospital of Anhui Medical University (The First People's Hospital of Hefei), 390 Huaihe Road, Hefei 230061, Anhui, China
| | - Zheng Zhu
- Department of Orthopedics, The Third Affiliated Hospital of Anhui Medical University (The First People's Hospital of Hefei), 390 Huaihe Road, Hefei 230061, Anhui, China
| | - Peizhi Lu
- Department of Orthopedics, The Third Affiliated Hospital of Anhui Medical University (The First People's Hospital of Hefei), 390 Huaihe Road, Hefei 230061, Anhui, China; Department of Orthopedics, Bengbu Medical College, Bengbu City 233000, China
| | - Run Fang
- Department of Orthopedics, The Third Affiliated Hospital of Anhui Medical University (The First People's Hospital of Hefei), 390 Huaihe Road, Hefei 230061, Anhui, China
| | - Cheng Peng
- Department of Orthopedics, The Third Affiliated Hospital of Anhui Medical University (The First People's Hospital of Hefei), 390 Huaihe Road, Hefei 230061, Anhui, China
| | - Jun Tong
- Department of Orthopedics, The Third Affiliated Hospital of Anhui Medical University (The First People's Hospital of Hefei), 390 Huaihe Road, Hefei 230061, Anhui, China
| | - Rende Ning
- Department of Orthopedics, The Third Affiliated Hospital of Anhui Medical University (The First People's Hospital of Hefei), 390 Huaihe Road, Hefei 230061, Anhui, China; Department of Orthopedics, Bengbu Medical College, Bengbu City 233000, China.
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Raj P, Wu L, Almeida C, Conway L, Tanwar S, Middendorf J, Barman I. Shining Light on Osteoarthritis: Spatially Offset Raman Spectroscopy as a Window into Cartilage Health. ACS Sens 2024; 9:3794-3804. [PMID: 38976969 DOI: 10.1021/acssensors.4c01242] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/10/2024]
Abstract
Articular cartilage is a complex tissue, and early detection of osteoarthritis (OA) is crucial for effective treatment. However, current imaging modalities lack molecular specificity and primarily detect late-stage changes. In this study, we propose the use of spatially offset Raman spectroscopy (SORS) for noninvasive, depth-dependent, and molecular-specific diagnostics of articular cartilage. We demonstrate the potential of SORS to penetrate deep layers of cartilage, providing a comprehensive understanding of disease progression. Our SORS measurements were characterized and validated through mechanical and histological techniques, revealing strong correlations between spectroscopic measurements and both Young's modulus and depth of cartilage damage. By longitudinally monitoring enzymatically degraded condyles, we further developed a depth-dependent damage-tracking method. Our analysis revealed distinct components related to sample depth and glycosaminoglycan (GAG) changes, offering a comprehensive picture of cartilage health. Collectively, these findings highlight the potential of SORS as a valuable tool for enhancing OA management and improving patient outcomes.
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Affiliation(s)
- Piyush Raj
- Department of Mechanical Engineering, Johns Hopkins University, Baltimore, Maryland 21218, United States
| | - Lintong Wu
- Department of Mechanical Engineering, Johns Hopkins University, Baltimore, Maryland 21218, United States
| | - Craig Almeida
- Department of Mechanical Engineering, Johns Hopkins University, Baltimore, Maryland 21218, United States
| | - Lauren Conway
- Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, Maryland 21218, United States
| | - Swati Tanwar
- Department of Mechanical Engineering, Johns Hopkins University, Baltimore, Maryland 21218, United States
| | - Jill Middendorf
- Department of Mechanical Engineering, Johns Hopkins University, Baltimore, Maryland 21218, United States
| | - Ishan Barman
- Department of Mechanical Engineering, Johns Hopkins University, Baltimore, Maryland 21218, United States
- The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University, School of Medicine, Baltimore, Maryland 21205, United States
- Department of Oncology, Johns Hopkins University, Baltimore, Maryland 21287, United States
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O'Sullivan O, Behan FP, Coppack RJ, Stocks J, Kluzek S, Valdes AM, Bennett AN. Osteoarthritis in the UK Armed Forces: a review of its impact, treatment and future research. BMJ Mil Health 2024; 170:359-364. [PMID: 37491135 DOI: 10.1136/military-2023-002390] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2023] [Accepted: 05/31/2023] [Indexed: 07/27/2023]
Abstract
Within the UK Armed Forces, musculoskeletal injuries account for over half of all medical downgrades and discharges. Data from other Armed Forces show that osteoarthritis (OA), more common in military personnel, is likely to contribute to this, both in its primary form and following injury (post-traumatic OA, PTOA), which typically presents in the third or fourth decade. OA is not a progressive 'wear and tear' disease, as previously thought, but a heterogenous condition with multiple aetiologies and modulators, including joint damage, abnormal morphology, altered biomechanics, genetics, low-grade inflammation and dysregulated metabolism. Currently, clinical diagnosis, based on symptomatic or radiological criteria, is followed by supportive measures, including education, exercise, analgesia, potentially surgical intervention, with a particular focus on exercise rehabilitation within the UK military. Developments in OA have led to a new paradigm of organ failure, with an emphasis on early diagnosis and risk stratification, prevention strategies (primary, secondary and tertiary) and improved aetiological classification using genotypes and phenotypes to guide management, with the introduction of biological markers (biomarkers) potentially having a role in all these areas. In the UK Armed Forces, there are multiple research studies focused on OA risk factors, epidemiology, biomarkers and effectiveness of different interventions. This review aims to highlight OA, especially PTOA, as an important diagnosis to consider in serving personnel, outline current and future management options, and detail current research trends within the Defence Medical Services.
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Affiliation(s)
- Oliver O'Sullivan
- Academic Department of Military Rehabilitation, DMRC Stanford Hall, Loughborough, LE12 5QW, UK
- Academic Unit of Injury, Recovery and Inflammation Sciences, University of Nottingham, Nottingham, UK
| | - F P Behan
- Department of Bioengineering, Imperial College London, London, UK
| | - R J Coppack
- Academic Department of Military Rehabilitation, DMRC Stanford Hall, Loughborough, LE12 5QW, UK
- Centre for Sport, Exercise and Osteoarthritis Research, Versus Arthritis, Nottingham, UK
| | - J Stocks
- Academic Unit of Injury, Recovery and Inflammation Sciences, University of Nottingham, Nottingham, UK
| | - S Kluzek
- Academic Unit of Injury, Recovery and Inflammation Sciences, University of Nottingham, Nottingham, UK
- Centre for Sport, Exercise and Osteoarthritis Research, Versus Arthritis, Nottingham, UK
| | - A M Valdes
- Academic Unit of Injury, Recovery and Inflammation Sciences, University of Nottingham, Nottingham, UK
- Department of Twin Research and Genetic Epidemiology, King's College London, London, UK
| | - A N Bennett
- Academic Department of Military Rehabilitation, DMRC Stanford Hall, Loughborough, LE12 5QW, UK
- National Heart and Lung Institute, Faculty of Medicine, Imperial College London, London, UK
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Li Z, Leung KL, Huang C, Huang X, Su S, Chung RC, Ding C, Fu SN. Associations amongst dynamic knee stiffness during gait, quadriceps stiffness, and the incidence of knee osteoarthritis over 24 months: a cohort study with a mediation analysis. BMC Musculoskelet Disord 2024; 25:511. [PMID: 38961407 PMCID: PMC11220956 DOI: 10.1186/s12891-024-07618-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/26/2023] [Accepted: 06/21/2024] [Indexed: 07/05/2024] Open
Abstract
BACKGROUND Decreased strength and increased stiffness of the quadriceps have been associated with a higher risk of developing knee osteoarthritis (OA) in elders. Dynamic joint stiffness (DJS) represents collective resistance from active and passive knee structures for dynamic knee motions. Elevated sagittal knee DJS has been associated with worsening of cartilage loss in knee OA patients. Altered quadriceps properties may affect DJS, which could be a mediator for associations between quadriceps properties and knee OA. Hence, this study aimed to examine whether DJS and quadriceps properties would be associated with the development of clinical knee OA over 24 months, and to explore the mediation role of DJS in associations between quadriceps properties and knee OA. METHODS This was a prospective cohort study with 162 healthy community-dwelling elders. Gait analysis was conducted to compute DJS during the loading response phase. Quadriceps strength and stiffness were evaluated using a Cybex dynamometer and shear-wave ultrasound elastography, respectively. Knee OA was defined based on clinical criteria 24 months later. Logistic regression with generalized estimating equations was used to examine the association between quadriceps properties and DJS and incident knee OA. Mediation analysis was performed to explore the mediation role of DJS in associations between quadriceps properties and the incidence of knee OA. RESULTS A total of 125 participants (65.6 ± 4.0 years, 58.4% females) completed the 24-month follow-up, with 36 out of 250 knees identified as clinical knee OA. Higher DJS (OR = 1.86, 95%CI: 1.33-2.62), lower quadriceps strength (1.85, 1.05-3.23), and greater quadriceps stiffness (1.56, 1.10-2.21) were significantly associated with a higher risk of clinical knee OA. Mediation analysis showed that the DJS was not a significant mediator for the associations between quadriceps properties and knee OA. CONCLUSIONS Higher sagittal knee dynamic joint stiffness, lower quadriceps strength, and greater quadriceps stiffness are potential risk factors for developing clinical knee OA in asymptomatic elders. Associations between quadriceps properties and knee OA may not be mediated by dynamic joint stiffness. Interventions for reducing increased passive properties of the quadriceps and knee joint stiffness may be beneficial for maintaining healthy knees in the aging population.
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Affiliation(s)
- Zongpan Li
- Department of Rehabilitation Sciences, The Hong Kong Polytechnic University, 11 Yuk Choi Road, Hong Kong, Hong Kong, China
| | - Kam-Lun Leung
- Department of Rehabilitation Sciences, The Hong Kong Polytechnic University, 11 Yuk Choi Road, Hong Kong, Hong Kong, China
| | - Chen Huang
- Department of Rehabilitation Sciences, The Hong Kong Polytechnic University, 11 Yuk Choi Road, Hong Kong, Hong Kong, China
| | - Xiuping Huang
- Department of Rehabilitation Sciences, The Hong Kong Polytechnic University, 11 Yuk Choi Road, Hong Kong, Hong Kong, China
| | - Shan Su
- Department of Rehabilitation Sciences, The Hong Kong Polytechnic University, 11 Yuk Choi Road, Hong Kong, Hong Kong, China
| | - Raymond Ck Chung
- Department of Rehabilitation Sciences, The Hong Kong Polytechnic University, 11 Yuk Choi Road, Hong Kong, Hong Kong, China
| | - Changhai Ding
- Clinical Research Centre, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China
| | - Siu-Ngor Fu
- Department of Rehabilitation Sciences, The Hong Kong Polytechnic University, 11 Yuk Choi Road, Hong Kong, Hong Kong, China.
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Xu H, Liu S, Wei Y, Cao S, Deng J, Li G, Sheng W, Qi T, Zhang P, Lin J, Weng J, Yu F, Xiong A, Wang D, Zeng H, Chen Y, Yang J, Liu P. Curcumin-loaded biomimetic nanosponges for osteoarthritis alleviation by synergistically suppressing inflammation and ferroptosis. CHEMICAL ENGINEERING JOURNAL 2024; 491:152132. [DOI: 10.1016/j.cej.2024.152132] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/07/2024]
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Ostojic M, Oliveira JP, Kordic D, Mouton C, Prill R, Becker R. Blood and urine biomarkers for the diagnosis of early stages of knee osteoarthritis: A systematic review. J Exp Orthop 2024; 11:e12105. [PMID: 39076848 PMCID: PMC11284962 DOI: 10.1002/jeo2.12105] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2024] [Revised: 06/22/2024] [Accepted: 07/01/2024] [Indexed: 07/31/2024] Open
Abstract
Purpose To identify biomarkers in human blood or urine at an early stage of knee osteoarthritis (OA) and to elucidate if any can accurately differentiate between healthy controls and early knee OA patients and be considered as a candidate for widespread clinical use for early diagnosis of the disease. Methods Medline, Embase and Web of Science were screened to identify comparative studies measuring differences in blood or urine biomarkers between healthy controls and knee OA patients at an early stage (grade 1 or 2 Kellgren-Laurence). Two independent reviewers screened the abstracts for eligibility, reviewed the full texts, assessed the methodological quality and extracted the data. The Joanna Briggs Institute critical appraisal tool for diagnostic test accuracy studies was used to assess the quality of the included studies. Due to relevant heterogeneity, meta-analysis was not appropriate. Results Five studies met the eligibility criteria. The examined biomarkers were adropin, collagen type II metabolite, C-terminal cross-linked telopeptide of type II collagen, C-terminal cross-linked telopeptide of type I collagen, cartilage oligomeric matrix protein, matrix metalloproteinase 3, N-terminal propeptide of procollagen type IIA, type I procollagen N-terminal propeptides, N-terminal osteocalcin, angiopoietin-2, follistatin, granulocyte colony-stimulating factor, hepatocyte growth factor, interleukin-8, leptin, platelet-derived growth factor-BB, platelet endothelial cell adhesion molecule-1, vascular endothelial growth factor and calprotectin and totalling 19 biomarkers. All of the biomarkers were studied only once in the selected papers. Conclusions There is no reliable biomarker available to differentiate between early knee OA in patients and healthy controls, but a potential role of a cluster of biomarkers to close this gap. There are several limitations, including inappropriate study designs, small sample sizes, nonconsecutive patient groups and inadequate statistical methods for evaluating biomarker performance in studies included. Level of Evidence Level III.
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Affiliation(s)
- Marko Ostojic
- Department of Orthopaedics and TraumatologyUniversity Hospital MostarMostarBosnia and Herzegovina
- Osteon OrthopedicsTrauma and Sports Medicine ClinicMostarBosnia and Herzegovina
| | - Joao Pedro Oliveira
- Faculty of MedicineUniversity of CoimbraCoimbraPortugal
- Orthopaedic Department, Hospitais da Universidade de CoimbraUnidade Local de Saúde de CoimbraCoimbraPortugal
| | - David Kordic
- Department of Orthopaedics and TraumatologyUniversity Hospital MostarMostarBosnia and Herzegovina
| | - Caroline Mouton
- Department of Orthopaedic SurgeryCentre Hospitalier Luxembourg—Clinique d'EichLuxembourg CityLuxembourg
| | - Robert Prill
- Center of Orthopaedics and TraumatologyUniversity Hospital Brandenburg/Havel, Brandenburg Medical SchoolBrandenburg an der HavelGermany
- Brandenburg Medical School, Faculty of Health Sciences BrandenburgBrandenburg an der HavelGermany
| | - Roland Becker
- Center of Orthopaedics and TraumatologyUniversity Hospital Brandenburg/Havel, Brandenburg Medical SchoolBrandenburg an der HavelGermany
- Brandenburg Medical School, Faculty of Health Sciences BrandenburgBrandenburg an der HavelGermany
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50
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Cai R, Jiang Q, Chen D, Feng Q, Liang X, Ouyang Z, Liao W, Zhang R, Fang H. Identification of osteoblastic autophagy-related genes for predicting diagnostic markers in osteoarthritis. iScience 2024; 27:110130. [PMID: 38952687 PMCID: PMC11215306 DOI: 10.1016/j.isci.2024.110130] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2024] [Revised: 04/15/2024] [Accepted: 05/24/2024] [Indexed: 07/03/2024] Open
Abstract
The development of osteoarthritis (OA) involves subchondral bone lesions, but the role of osteoblastic autophagy-related genes (ARGs) in osteoarthritis is unclear. Through integrated analysis of single-cell dataset, Bulk RNA dataset, and 367 ARGs extracted from GeneCards, 40 ARGs were found. By employing multiple machine learning algorithms and PPI networks, three key genes (DDIT3, JUN, and VEGFA) were identified. Then the RF model constructed from these genes indicated great potential as a diagnostic tool. Furthermore, the model's effectiveness in predicting OA has been confirmed through external validation datasets. Moreover, the expression of ARGs was examined in osteoblasts subject to excessive mechanical stress, human and mouse tissues. Finally, the role of ARGs in OA was confirmed through co-culturing explants and osteoblasts. Thus, osteoblastic ARGs could be crucial in OA development, providing potential diagnostic and treatment strategies.
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Affiliation(s)
- Rulong Cai
- Department of Joint Surgery, Center for Orthopedic Surgery, The Third Affiliated Hospital, Southern Medical University, Guangzhou, 510630, China
- Academy of Orthopedics · Guangdong Province, Guangzhou, 510630, China
- Orthopedic Hospital of Guangdong Province, Guangzhou, 510630, China
- Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, Guangzhou, 510630, China
- The Third School of Clinical Medicine, Southern Medical University, Guangzhou, 510515, China
| | - Qijun Jiang
- The Third School of Clinical Medicine, Southern Medical University, Guangzhou, 510515, China
- Department of Urology, The Third Affiliated Hospital, Southern Medical University, Guangzhou, 510630, China
| | - Dongli Chen
- Department of Ultrasound, The University of Hong Kong-Shenzhen Hospital, Shenzhen, 518053, China
| | - Qi Feng
- Department of Joint Surgery, Center for Orthopedic Surgery, The Third Affiliated Hospital, Southern Medical University, Guangzhou, 510630, China
- Academy of Orthopedics · Guangdong Province, Guangzhou, 510630, China
- Orthopedic Hospital of Guangdong Province, Guangzhou, 510630, China
- Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, Guangzhou, 510630, China
- The Third School of Clinical Medicine, Southern Medical University, Guangzhou, 510515, China
| | - Xinzhi Liang
- Department of Joint Surgery, Center for Orthopedic Surgery, The Third Affiliated Hospital, Southern Medical University, Guangzhou, 510630, China
- Academy of Orthopedics · Guangdong Province, Guangzhou, 510630, China
- Orthopedic Hospital of Guangdong Province, Guangzhou, 510630, China
- Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, Guangzhou, 510630, China
- The Third School of Clinical Medicine, Southern Medical University, Guangzhou, 510515, China
| | - Zhaoming Ouyang
- Department of Joint Surgery, Center for Orthopedic Surgery, The Third Affiliated Hospital, Southern Medical University, Guangzhou, 510630, China
- Academy of Orthopedics · Guangdong Province, Guangzhou, 510630, China
- Orthopedic Hospital of Guangdong Province, Guangzhou, 510630, China
- Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, Guangzhou, 510630, China
- The Third School of Clinical Medicine, Southern Medical University, Guangzhou, 510515, China
| | - Weijian Liao
- Department of Joint Surgery, Center for Orthopedic Surgery, The Third Affiliated Hospital, Southern Medical University, Guangzhou, 510630, China
- Academy of Orthopedics · Guangdong Province, Guangzhou, 510630, China
- Orthopedic Hospital of Guangdong Province, Guangzhou, 510630, China
- Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, Guangzhou, 510630, China
- The Third School of Clinical Medicine, Southern Medical University, Guangzhou, 510515, China
| | - Rongkai Zhang
- Department of Joint Surgery, Center for Orthopedic Surgery, The Third Affiliated Hospital, Southern Medical University, Guangzhou, 510630, China
- Academy of Orthopedics · Guangdong Province, Guangzhou, 510630, China
- Orthopedic Hospital of Guangdong Province, Guangzhou, 510630, China
- Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, Guangzhou, 510630, China
- The Third School of Clinical Medicine, Southern Medical University, Guangzhou, 510515, China
| | - Hang Fang
- Department of Joint Surgery, Center for Orthopedic Surgery, The Third Affiliated Hospital, Southern Medical University, Guangzhou, 510630, China
- Academy of Orthopedics · Guangdong Province, Guangzhou, 510630, China
- Orthopedic Hospital of Guangdong Province, Guangzhou, 510630, China
- Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, Guangzhou, 510630, China
- The Third School of Clinical Medicine, Southern Medical University, Guangzhou, 510515, China
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