|
1
|
El Hajjaji A, Akasbi N, El Mezouar I, Harzy T. Does Statin Therapy Have a Beneficial Effect on Knee Osteoarthritis? Cureus 2025; 17:e79420. [PMID: 40130094 PMCID: PMC11930770 DOI: 10.7759/cureus.79420] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/21/2025] [Indexed: 03/26/2025] Open
Abstract
INTRODUCTION Knee osteoarthritis (KO) is a major public health issue, that significantly affects patients' quality of life. Metabolic comorbidities, particularly dyslipidemia, have been shown to influence the incidence and progression of KO. Given the potential impact of hypercholesterolemia on disease progression, the hypothesis arises that dyslipidemia treatments, such as statins, may offer a beneficial effect in mitigating KO progression. Objective: This study evaluates the effect of statin therapy on the clinical improvement of knee osteoarthritis (KO), particularly in terms of pain reduction, measured using the Visual Analog Scale (VAS). METHODS A cross-sectional, retrospective, descriptive, and analytical study was conducted at the rheumatology department of the University Hospital Center Hassan II of Fez, between January 2018 and January 2024. Patients diagnosed with symptomatic primary knee osteoarthritis (KO) were recruited from the department's database of rheumatology consultations, and all were regularly followed up within the department. The patients were divided into two groups: Group 1, which received statin therapy, and Group 0, a control group that did not receive statins. The primary outcome was clinical improvement, which was assessed using the Visual Analog Scale (VAS) to measure pain intensity. RESULTS A total of 465 patients were included, with 48 (10.3%) receiving statins. A significant clinical improvement in KO was observed in 34 (70.8%) patients in the statin group, compared to 196 (47.1%) patients in the control group (p=0.001). The analysis indicated that statin use was significantly associated with clinical improvement, independent of other demographic and comorbid factors. CONCLUSIONS Statin use may provide benefits in the management of KO, particularly in reducing pain, in addition to conventional symptomatic treatments. These results highlight the need for further prospective research to clarify the mechanisms of action of statins in this condition.
Collapse
Affiliation(s)
- Abla El Hajjaji
- Rheumatology, Hassan II University Hospital, Faculty of Medicine, Pharmacy and Dental Medicine, Sidi Mohamed Ben Abdellah University, Fez, MAR
| | - Nessrine Akasbi
- Rheumatology, Hassan II University Hospital, Faculty of Medicine, Pharmacy and Dental Medicine, Sidi Mohamed Ben Abdellah University, Fez, MAR
| | - Imane El Mezouar
- Rheumatology, Hassan II University Hospital, Faculty of Medicine, Pharmacy and Dental Medicine, Sidi Mohamed Ben Abdellah University, Fez, MAR
| | - Taoufik Harzy
- Rheumatology, Hassan II University Hospital, Faculty of Medicine, Pharmacy and Dental Medicine, Sidi Mohamed Ben Abdellah University, Fez, MAR
| |
Collapse
|
|
2
|
Ma G, Xu B, Wang Z, Duan W, Chen X, Zhu L, Yang B, Zhang D, Qin X, Yin H, Wei X. Non-linear association of sleep duration with osteoarthritis among U.S. middle-aged and older adults. BMC Public Health 2024; 24:3565. [PMID: 39716177 DOI: 10.1186/s12889-024-21140-1] [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: 10/07/2024] [Accepted: 12/18/2024] [Indexed: 12/25/2024] Open
Abstract
BACKGROUND The duration of sleep is linked to a range of disorders. Osteoarthritis (OA) stands as one of the most prevalent forms of arthritis and serves as a leading cause of disability. The correlation between the duration of sleep and OA remains ambiguous. Research indicates that waist circumference correlates with sleep duration and OA, respectively. This study aimed to investigate the association of sleep duration with OA and the mediated effect of waist circumference. METHODS The study sample comprised adults who were participants in the National Health and Nutrition Examination Survey (NHANES) between 2011 and 2018. Insufficient sleep is characterized by a duration of less than seven hours, whereas 7-8 h is considered appropriate, and 9 h or more is categorized as a long sleep duration. Three models were employed in this study. Model 1 was not adjusted for any covariates, while Model 2 was adjusted for sex, age, and race. Model 3 has been adjusted to account for all covariates. Utilizing multivariable logistic regression, subgroup analysis, interaction tests and smoothing curve fitting, the correlation between sleep duration and OA was explored. The mediating effect of waist circumference on the association between sleep duration and OA was investigated through mediation analysis. RESULTS In this study, 9380 did not have OA, while 2424 were diagnosed with the ailment. After multivariable adjustment, the odds ratios (OR) for OA were 1.19 (95% CI 1.06, 1.34; P = 0.0026) for people with insufficient sleep duration and 1.18 (95% CI 1.03, 1.35 P = 0.0142) for participants with long sleep duration. Sleep duration and the incidence of OA were found to be related in a U-shaped manner. Additionally, 12.1% of the correlation between sleep duration and OA appeared to be mediated by waist circumference. CONCLUSIONS Increased OA was found to be correlated in a U-shaped manner with sleep duration in the middle-aged and elderly cohorts. Both insufficient and long sleep duration contribute to an elevated risk of developing OA. A potential mediating factor in the association between OA and sleep duration is waist circumference. Focus on sleep health and visceral obesity in middle-aged and older adults is necessary.
Collapse
Affiliation(s)
- Guoliang Ma
- Wangjing Hospital, China Academy of Chinese Medical Sciences, No. 6, Zhonghuan South Road, Chaoyang District, Beijing, 100102, China
| | - Bo Xu
- Wangjing Hospital, China Academy of Chinese Medical Sciences, No. 6, Zhonghuan South Road, Chaoyang District, Beijing, 100102, China
| | - Zhizhuang Wang
- Wangjing Hospital, China Academy of Chinese Medical Sciences, No. 6, Zhonghuan South Road, Chaoyang District, Beijing, 100102, China
| | - Weili Duan
- Nanyang Hospital of Traditional Chinese Medicine (Dushan Campus), Henan , 473003, China
| | - Xin Chen
- Wangjing Hospital, China Academy of Chinese Medical Sciences, No. 6, Zhonghuan South Road, Chaoyang District, Beijing, 100102, China
| | - Liguo Zhu
- Wangjing Hospital, China Academy of Chinese Medical Sciences, No. 6, Zhonghuan South Road, Chaoyang District, Beijing, 100102, China
- Beijing Key Laboratory of Bone Setting Technology of Traditional Chinese Medicine, Beijing, 100700, China
| | - Bowen Yang
- Wangjing Hospital, China Academy of Chinese Medical Sciences, No. 6, Zhonghuan South Road, Chaoyang District, Beijing, 100102, China
| | - Dian Zhang
- Wangjing Hospital, China Academy of Chinese Medical Sciences, No. 6, Zhonghuan South Road, Chaoyang District, Beijing, 100102, China
| | - Xiaokuan Qin
- Wangjing Hospital, China Academy of Chinese Medical Sciences, No. 6, Zhonghuan South Road, Chaoyang District, Beijing, 100102, China
| | - He Yin
- Wangjing Hospital, China Academy of Chinese Medical Sciences, No. 6, Zhonghuan South Road, Chaoyang District, Beijing, 100102, China.
| | - Xu Wei
- Wangjing Hospital, China Academy of Chinese Medical Sciences, No. 6, Zhonghuan South Road, Chaoyang District, Beijing, 100102, China.
| |
Collapse
|
|
3
|
Segal NA, Nilges JM, Oo WM. Sex differences in osteoarthritis prevalence, pain perception, physical function and therapeutics. Osteoarthritis Cartilage 2024; 32:1045-1053. [PMID: 38588890 DOI: 10.1016/j.joca.2024.04.002] [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: 11/15/2023] [Revised: 03/19/2024] [Accepted: 04/02/2024] [Indexed: 04/10/2024]
Abstract
OBJECTIVE Women have a higher prevalence of osteoarthritis (OA) and worse clinical courses than men. However, the underlying factors and therapeutic outcomes of these sex-specific differences are incompletely researched. This review examines the current state of knowledge regarding sex differences in OA prevalence, risk factors, pain severity, functional outcomes, and use and response to therapeutics. METHODS PubMed database was used with the title keyword combinations "{gender OR sex} AND osteoarthritis" plus additional manual search of the included papers for pertinent references, yielding 212 references. Additional references were added and 343 were reviewed for appropriateness. RESULTS Globally, women account for 60% of people with osteoarthritis, with a greater difference after age 40. The higher risk for women may be due to differences in joint anatomy, alignment, muscle strength, hormonal influences, obesity, and/or genetics. At the same radiographic severity, women have greater pain severity than men, which may be explained by biologically distinct pain pathways, differential activation of central pain pathways, differences in pain sensitivity, perception, reporting, and coping strategies. Women have greater limitations of physical function and performance than men independent of BMI, OA severity, injury history, and amount of weekly exercise. Women also have greater use of analgesic medications than men but less use of arthroplasty and poorer prognosis after surgical interventions. CONCLUSIONS The recognition of sex differences in OA manifestations and management could guide tailoring of sex-specific treatment protocols, and analysis of sex as a biological variable in future research would enhance development of precision medicine.
Collapse
Affiliation(s)
- Neil A Segal
- University of Kansas Medical Center, Kansas City, KS, USA; The University of Iowa, Iowa City, IA, USA.
| | | | - Win Min Oo
- The University of Sydney, Sydney, Australia; University of Medicine, Mandalay, Mandalay, Myanmar.
| |
Collapse
|
|
4
|
Power JD, Perruccio AV, Canizares M, Davey JR, Gandhi R, Mahomed NN, Syed K, Veillette C, Rampersaud YR. The impact of diabetes status on pain and physical function following total joint arthroplasty for hip and knee osteoarthritis: variation by sex and body mass index. Sci Rep 2024; 14:11152. [PMID: 38750058 PMCID: PMC11096302 DOI: 10.1038/s41598-024-61847-0] [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: 12/20/2023] [Accepted: 05/10/2024] [Indexed: 05/18/2024] Open
Abstract
Few studies have examined diabetes impact on total joint arthroplasty (TJA) outcomes, with variable findings. We investigated the association between diabetes and post-TJA physical function and pain, examining whether diabetes impact differs by sex and BMI. Patient sample completed questionnaires within 3 months prior to hip or knee TJA for osteoarthritis (OA) and 1-year post-surgery. Surgical 'non-response' was defined as < 30% improvement in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain and physical function at 1-year. Two adjusted logistic regression models were estimated: (1) excluding, (2) including an interaction between diabetes, sex and BMI. The sample (626 hip, 754 knee) was 54.9% female, had mean BMI of 30.1, 13.0% reported diabetes. In adjusted models excluding an interaction, diabetes was not associated with non-response. However, a significant 3-way interaction (physical function: p = 0.003; pain: p = 0.006) between diabetes, sex, and BMI was found and was associated with non-response: non-response probability increased with increasing BMI in men with diabetes, but decreased with increasing BMI in women in diabetes. Findings suggest uncertainty in diabetes impact may be due to differential impacts by sex and BMI. A simple consideration of diabetes as present vs. absent may not be sufficient, with implications for the large TJA population.
Collapse
Affiliation(s)
- J Denise Power
- Schroeder Arthritis Institute, Krembil Research Institute, University Health Network, 399 Bathurst Street MP10-326, Toronto, ON, M5T 2S8, Canada.
- Arthritis Community Research & Epidemiology Unit, Toronto, ON, Canada.
| | - Anthony V Perruccio
- Schroeder Arthritis Institute, Krembil Research Institute, University Health Network, 399 Bathurst Street MP10-326, Toronto, ON, M5T 2S8, Canada
- Arthritis Community Research & Epidemiology Unit, Toronto, ON, Canada
- Orthopaedics, Department of Surgery, University of Toronto, Toronto, ON, Canada
- Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, ON, Canada
| | - Mayilee Canizares
- Schroeder Arthritis Institute, Krembil Research Institute, University Health Network, 399 Bathurst Street MP10-326, Toronto, ON, M5T 2S8, Canada
- Arthritis Community Research & Epidemiology Unit, Toronto, ON, Canada
| | - J Roderick Davey
- Schroeder Arthritis Institute, Krembil Research Institute, University Health Network, 399 Bathurst Street MP10-326, Toronto, ON, M5T 2S8, Canada
- Orthopaedics, Department of Surgery, University of Toronto, Toronto, ON, Canada
| | - Rajiv Gandhi
- Schroeder Arthritis Institute, Krembil Research Institute, University Health Network, 399 Bathurst Street MP10-326, Toronto, ON, M5T 2S8, Canada
- Orthopaedics, Department of Surgery, University of Toronto, Toronto, ON, Canada
| | - Nizar N Mahomed
- Schroeder Arthritis Institute, Krembil Research Institute, University Health Network, 399 Bathurst Street MP10-326, Toronto, ON, M5T 2S8, Canada
- Orthopaedics, Department of Surgery, University of Toronto, Toronto, ON, Canada
- ICES, Toronto, ON, Canada
| | - Khalid Syed
- Schroeder Arthritis Institute, Krembil Research Institute, University Health Network, 399 Bathurst Street MP10-326, Toronto, ON, M5T 2S8, Canada
- Orthopaedics, Department of Surgery, University of Toronto, Toronto, ON, Canada
| | - Christian Veillette
- Schroeder Arthritis Institute, Krembil Research Institute, University Health Network, 399 Bathurst Street MP10-326, Toronto, ON, M5T 2S8, Canada
- Orthopaedics, Department of Surgery, University of Toronto, Toronto, ON, Canada
| | - Y Raja Rampersaud
- Schroeder Arthritis Institute, Krembil Research Institute, University Health Network, 399 Bathurst Street MP10-326, Toronto, ON, M5T 2S8, Canada
- Orthopaedics, Department of Surgery, University of Toronto, Toronto, ON, Canada
- Neurosurgery, Department of Surgery, University of Toronto, Toronto, ON, Canada
| |
Collapse
|
|
5
|
Primrose JG, Jain L, Bolam SM, Monk AP, Munro JT, Dalbeth N, Poulsen RC. Concentration-dependent effects of leptin on osteoarthritis-associated changes in phenotype of human chondrocytes. Connect Tissue Res 2023; 64:457-468. [PMID: 37171229 DOI: 10.1080/03008207.2023.2214249] [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: 01/19/2023] [Accepted: 05/10/2023] [Indexed: 05/13/2023]
Abstract
Metabolic syndrome is a risk factor for osteoarthritis. Elevated leptin levels have been implicated as a potential cause of this association. Previous studies have shown that supra-physiological leptin concentrations can induce osteoarthritis-like changes in chondrocyte phenotype. Here, we tested the effects of leptin in the concentration range found in synovial fluid on chondrocyte phenotype. Chondrocytes isolated from macroscopically normal regions of cartilage within osteoarthritic joints from patients undergoing knee arthroplasty, all with body mass index >30 kg/m2 were treated with 2-40 ng/ml leptin for 24 h. Chondrocyte phenotype marker expression was measured by RT-qPCR and western blot. The role of HES1 in mediating the effects of leptin was determined by gene knockdown using RNAi and over-expression using adenoviral-mediated gene delivery. Treatment of chondrocytes with 20 or 40 ng/ml leptin resulted in decreased SOX9 levels and decreased levels of the SOX9-target genes COL2A1 and ACAN. Levels of HES1 were lower and ADAMTS5 higher in chondrocytes treated with 20 or 40 ng/ml leptin. HES1 knockdown resulted in increased ADAMTS5 expression whereas over-expression of HES1 prevented the leptin-induced increase in ADAMTS5. An increase in MMP13 expression was only evident in chondrocytes treated with 40 ng/ml leptin and was not mediated by HES1 activity. High concentrations of leptin can cause changes in chondrocyte phenotype consistent with those seen in osteoarthritis. Synovial fluid leptin concentrations of this level are typically observed in patients with metabolic syndrome and/or women, suggesting elevated leptin levels may form part of the multifactorial network that leads to osteoarthritis development in these patients.
Collapse
Affiliation(s)
- Julia Gb Primrose
- Department of Pharmacology and Clinical Pharmacology, University of Auckland, Auckland, New Zealand
| | - Lekha Jain
- Department of Pharmacology and Clinical Pharmacology, University of Auckland, Auckland, New Zealand
| | - Scott M Bolam
- Department of Surgery, University of Auckland, Auckland, New Zealand
- Department of Medicine, University of Auckland, Auckland, New Zealand
| | - A Paul Monk
- Auckland Bioengineering Institute, University of Auckland, Auckland, New Zealand
| | - Jacob T Munro
- Department of Surgery, University of Auckland, Auckland, New Zealand
| | - Nicola Dalbeth
- Department of Medicine, University of Auckland, Auckland, New Zealand
| | - Raewyn C Poulsen
- Department of Pharmacology and Clinical Pharmacology, University of Auckland, Auckland, New Zealand
- Department of Medicine, University of Auckland, Auckland, New Zealand
| |
Collapse
|
|
6
|
Shumnalieva R, Kotov G, Monov S. Obesity-Related Knee Osteoarthritis-Current Concepts. Life (Basel) 2023; 13:1650. [PMID: 37629507 PMCID: PMC10456094 DOI: 10.3390/life13081650] [Citation(s) in RCA: 32] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2023] [Revised: 07/23/2023] [Accepted: 07/25/2023] [Indexed: 08/27/2023] Open
Abstract
The knee is the joint most frequently involved in osteoarthritis and represents a significant contributor to patient morbidity and impaired functional status. Major risk factors include genetics, age, sex, mechanical load and obesity/metabolic syndrome. Recent studies highlighted the role of obesity and metabolic syndrome in the pathogenesis of knee osteoarthritis not simply through increased mechanical loading but the systemic effects of obesity-induced inflammation. The current concept of knee osteoarthritis is that of a 'whole joint disease', which highlights the involvement not only of articular cartilage but also the synovium, subchondral bone, ligaments and muscles. Obesity and metabolic syndrome are associated with higher levels of pro-inflammatory cytokines, increased production of adipokines with both protective and destructive effects on articular cartilage, an up-regulation of proteolytic enzymes such as matrix metalloproteinases and aggrecanases and an increase in free fatty acids and reactive oxygen species induced by dyslipidemia. These findings underscore that the adequate management of knee osteoarthritis needs to include an optimization of body weight and a beneficial mobility regimen. The possible introduction of pharmacological therapy targeting specific molecules involved in the pathogenesis of obesity-related osteoarthritis will likely also be considered in future therapeutic strategies, including personalized treatment approaches.
Collapse
Affiliation(s)
| | - Georgi Kotov
- Clinic of Rheumatology, Department of Rheumatology, Medical University of Sofia, 1431 Sofia, Bulgaria; (R.S.); (S.M.)
| | | |
Collapse
|
|
7
|
Fu Y, Batushansky A, Kinter M, Huebner JL, Kraus VB, Griffin TM. Effects of Leptin and Body Weight on Inflammation and Knee Osteoarthritis Phenotypes in Female Rats. JBMR Plus 2023; 7:e10754. [PMID: 37457883 PMCID: PMC10339097 DOI: 10.1002/jbm4.10754] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2023] [Revised: 03/22/2023] [Accepted: 04/13/2023] [Indexed: 07/18/2023] Open
Abstract
Leptin is a proinflammatory adipokine that contributes to obesity-associated osteoarthritis (OA), especially in women. However, the extent to which leptin causes knee OA separate from the effect of increased body weight is not clear. We hypothesized that leptin is necessary to induce knee OA in obese female rats but not sufficient to induce knee OA in lean rats lacking systemic metabolic inflammation. The effect of obesity without leptin signaling was modeled by comparing female lean Zucker rats to pair fed obese Zucker rats, which possess mutant fa alleles of the leptin receptor gene. The effect of leptin without obesity was modeled in female F344BN F1 hybrid rats by systemically administering recombinant rat leptin versus saline for 23 weeks via osmotic pumps. Primary OA outcomes included cartilage histopathology and subchondral bone micro-computed tomography. Secondary outcomes included targeted cartilage proteomics, serum inflammation, and synovial fluid inflammation following an acute intra-articular challenge with interleukin-1β (IL-1β). Compared to lean Zucker rats, obese Zucker rats developed more severe tibial osteophytes and focal cartilage lesions in the medial tibial plateau, with modest changes in proximal tibial epiphysis trabecular bone structure. In contrast, exogenous leptin treatment, which increased plasma leptin sixfold without altering body weight, caused mild generalized cartilage fibrillation and reduced Safranin O staining compared to vehicle-treated animals. Leptin also significantly increased subchondral and trabecular bone volume and bone mineral density in the proximal tibia. Cartilage metabolic and antioxidant enzyme protein levels were substantially elevated with leptin deficiency and minimally suppressed with leptin treatment. In contrast, leptin treatment induced greater changes in systemic and local inflammatory mediators compared to leptin receptor deficiency, including reduced serum IL-6 and increased synovial fluid IL-1β. In conclusion, rat models that separately elevate leptin or body weight develop distinct OA-associated phenotypes, revealing how obesity increases OA pathology through both leptin-dependent and independent pathways. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
Collapse
Affiliation(s)
- Yao Fu
- Aging and Metabolism Research ProgramOklahoma Medical Research FoundationOklahoma CityOklahomaUSA
| | - Albert Batushansky
- Aging and Metabolism Research ProgramOklahoma Medical Research FoundationOklahoma CityOklahomaUSA
| | - Michael Kinter
- Aging and Metabolism Research ProgramOklahoma Medical Research FoundationOklahoma CityOklahomaUSA
- Oklahoma Center for GeroscienceUniversity of Oklahoma Health Sciences CenterOklahoma CityOklahomaUSA
| | - Janet L. Huebner
- Duke Molecular Physiology InstituteDuke University, School of Medicine, Duke UniversityDurhamNorth CarolinaUSA
| | - Virginia B. Kraus
- Duke Molecular Physiology InstituteDuke University, School of Medicine, Duke UniversityDurhamNorth CarolinaUSA
- Division of Rheumatology, Department of MedicineDuke University, School of Medicine, Duke UniversityDurhamNorth CarolinaUSA
| | - Timothy M. Griffin
- Aging and Metabolism Research ProgramOklahoma Medical Research FoundationOklahoma CityOklahomaUSA
- Oklahoma Center for GeroscienceUniversity of Oklahoma Health Sciences CenterOklahoma CityOklahomaUSA
- Department of Biochemistry and Molecular BiologyUniversity of Oklahoma Health Sciences CenterOklahoma CityOklahomaUSA
- Veterans Affairs Medical CenterOklahoma CityOklahomaUSA
| |
Collapse
|
|
8
|
Morita Y, Kamatani Y, Ito H, Ikegawa S, Kawaguchi T, Kawaguchi S, Takahashi M, Terao C, Ito S, Nishitani K, Nakamura S, Kuriyama S, Tabara Y, Matsuda F, Matsuda S. Improved genetic prediction of the risk of knee osteoarthritis using the risk factor-based polygenic score. Arthritis Res Ther 2023; 25:103. [PMID: 37309008 PMCID: PMC10258963 DOI: 10.1186/s13075-023-03082-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2023] [Accepted: 06/01/2023] [Indexed: 06/14/2023] Open
Abstract
BACKGROUND Polygenic risk score (PRS) analysis is used to predict disease risk. Although PRS has been shown to have great potential in improving clinical care, PRS accuracy assessment has been mainly focused on European ancestry. This study aimed to develop an accurate genetic risk score for knee osteoarthritis (OA) using a multi-population PRS and leveraging a multi-trait PRS in the Japanese population. METHODS We calculated PRS using PRS-CS-auto, derived from genome-wide association study (GWAS) summary statistics for knee OA in the Japanese population (same ancestry) and multi-population. We further identified risk factor traits for which PRS could predict knee OA and subsequently developed an integrated PRS based on multi-trait analysis of GWAS (MTAG), including genetically correlated risk traits. PRS performance was evaluated in participants of the Nagahama cohort study who underwent radiographic evaluation of the knees (n = 3,279). PRSs were incorporated into knee OA integrated risk models along with clinical risk factors. RESULTS A total of 2,852 genotyped individuals were included in the PRS analysis. The PRS based on Japanese knee OA GWAS was not associated with knee OA (p = 0.228). In contrast, PRS based on multi-population knee OA GWAS showed a significant association with knee OA (p = 6.7 × 10-5, odds ratio (OR) per standard deviation = 1.19), whereas PRS based on MTAG of multi-population knee OA, along with risk factor traits such as body mass index GWAS, displayed an even stronger association with knee OA (p = 5.4 × 10-7, OR = 1.24). Incorporating this PRS into traditional risk factors improved the predictive ability of knee OA (area under the curve, 74.4% to 74.7%; p = 0.029). CONCLUSIONS This study showed that multi-trait PRS based on MTAG, combined with traditional risk factors, and using large sample size multi-population GWAS, significantly improved predictive accuracy for knee OA in the Japanese population, even when the sample size of GWAS of the same ancestry was small. To the best of our knowledge, this is the first study to show a statistically significant association between the PRS and knee OA in a non-European population. TRIAL REGISTRATION No. C278.
Collapse
Affiliation(s)
- Yugo Morita
- Department of Orthopedic Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan
- Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Yoichiro Kamatani
- Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Hiromu Ito
- Department of Orthopedic Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan.
- Department of Orthopedic Surgery, Kurashiki Central Hospital, Kurashiki, Japan.
| | - Shiro Ikegawa
- Laboratory for Bone and Joint Diseases, Center for Genomic Medicine, RIKEN, Tokyo, Japan
- Laboratory for Statistical and Translational Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
| | - Takahisa Kawaguchi
- Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Shuji Kawaguchi
- Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Meiko Takahashi
- Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Chikashi Terao
- Laboratory for Statistical and Translational Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
| | - Shuji Ito
- Laboratory for Bone and Joint Diseases, Center for Genomic Medicine, RIKEN, Tokyo, Japan
- Laboratory for Statistical and Translational Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
- Department of Orthopedic Surgery, Shimane University Faculty of Medicine, Izumo, Japan
| | - Kohei Nishitani
- Department of Orthopedic Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Shinichiro Nakamura
- Department of Orthopedic Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Shinichi Kuriyama
- Department of Orthopedic Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Yasuharu Tabara
- Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan
- Graduate School of Public Health, Shizuoka Graduate University of Public Health, Aoi-Ku, Shizuoka, Japan
| | - Fumihiko Matsuda
- Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Shuichi Matsuda
- Department of Orthopedic Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan
| |
Collapse
|
|
9
|
Ansari S, Saeed S. The combined role of diabetes and obesity in susceptibility to musculoskeletal disorders and its subtypes in older men and women in India. J Diabetes Metab Disord 2023; 22:835-846. [PMID: 37255835 PMCID: PMC10225444 DOI: 10.1007/s40200-023-01211-7] [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: 01/06/2023] [Accepted: 03/09/2023] [Indexed: 06/01/2023]
Abstract
Background and aims In later life, diabetes and obesity can cause a change in musculoskeletal systems that can lead to aching joints and a myriad of other musculoskeletal disorders such as arthritis, osteoporosis, rheumatism, bone fractures etc., resulting in significant morbidity including pain and disability. There is a paucity of research to know how comorbidity of diabetes and obesity increase musculoskeletal disorders among older people. Therefore, the present study used nationally representative data to examine the interaction of diabetes and obesity on musculoskeletal disorders and its subtypes including arthritis, osteoporosis, and rheumatism among older men and women in India. Methods Data were extracted from the first wave of the nationally representative survey Longitudinal Aging Study in India (LASI) conducted in 2017-18. The final sample includes 31,464 people aged 60 years or above. Primary outcome variable was any listed musculoskeletal disorders and secondary outcomes were its subtypes including arthritis, osteoporosis, and rheumatism based on self-reported questions. Diabetes and obesity based on anthropometric index of weight and height (i.e., body mass index (BMI) with a standard cut-off of 30 kg/m2 or over) were considered as explanatory variables of interest. Logistic regression was used to assess the relationship between diabetes and musculoskeletal disorders. Interaction analysis was performed by both additive and multiplicative scales. Results Comparing older people without diabetes, the prevalence of musculoskeletal disorders and its subtypes were higher among those with diabetes, particularly arthritis disorders in older women. Diabetes was significantly correlated with the risk of musculoskeletal disorders and its subtypes including arthritis and osteoporosis even after controlling potential factors. The combination of diabetes and obesity was significantly and positively associated with musculoskeletal disorders (aOR: 4.14; p-value < 0.0001; 95% CI: 1.96 to 8.74) and its subtype only arthritis (aOR: 4.36; p-value < 0.0001; 95% CI: 1.76 to 10.8) comparing to those without both the conditions. However, the association was strong for older women as compared to older men. Notwithstanding, multiplicative scale interaction showed statistically significant for musculoskeletal disorders and its three subtypes among older women, however it was not significant for osteoporosis and rheumatism disorders among older men. When we analyzed interaction on additive scale, we found it only for arthritis disorder among older women suggesting the risk from obesity (relative excess risk due to interaction (RERI): -0.83, 95% CI: -1.44 to -0.22, attributable proportion due to interaction (AP): -0.54, 95% CI: -1.05 to -0.03, synergy index (S): 0.39, 95% CI: 0.16 to 0.93) was additive to the risk from diabetes. Conclusions This study suggests an elevated risk of musculoskeletal disorders among Indian older adults with diabetes. The result of this study also suggests an interactive association of diabetes and obesity with musculoskeletal disorders, particularly with arthritis disorder. There is a need to pay attention to the BMI level while treating diabetes in Indian older population.
Collapse
Affiliation(s)
- Salmaan Ansari
- International Institute for Population Sciences, Mumbai, India
| | - Shazina Saeed
- Amity Institute of Public Health, Amity University, Noida, India
| |
Collapse
|
|
10
|
Zheng J, Huang X, Huang J, Meng B, Li F, Liu H, Chen L, Zhou R, Zou M, Wu X. Association of Diabetes Mellitus Status and Hyperglycemia With Symptomatic Knee Osteoarthritis. Arthritis Care Res (Hoboken) 2023; 75:509-518. [PMID: 35225437 DOI: 10.1002/acr.24872] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2021] [Revised: 02/12/2022] [Accepted: 02/22/2022] [Indexed: 02/05/2023]
Abstract
OBJECTIVE Emerging evidence indicates that hyperglycemia has an adverse impact on the knee joint which, in turn, may increase the risk of knee osteoarthritis (OA), but evidence from the real-life settings of large-scale cohort studies remains unclear. We sought to evaluate the association of glycemic control and the risk of symptomatic knee OA in a community-based cohort of older adults. METHODS We conducted a prospective analysis of 10,730 participants without knee OA. Comprehensive blood biomarker data were obtained. Diabetes mellitus (DM) was defined mainly using a glycosylated hemoglobin (HbA1c ) level of ≥6.5%; poor glycemic control in individuals with DM was defined as an HbA1c level of ≥7%. We fit Cox regression models, stratified according to DM status. We evaluated the hazards associated with HbA1c and fasting blood glucose levels using a spline model. RESULTS During a median follow-up of 5 years, knee OA developed in 1,089 participants (108 with DM and 971 without). Knee OA was related to DM (hazard ratio [HR] 1.29 [95% confidence interval (95% CI) 1.02-1.78]), bad glycemic regulation in DM patients (HR 1.41 [95% CI 1.05-2.09]), and long-term DM (≥5 versus <5 years; HR 1.49 [95% CI 1.02-2.17]). High levels of HbA1c (>7.7% and 61 mmoles/mole) and fasting blood glucose (>186 mg/dl) were significantly associated with higher risk of incident knee OA. CONCLUSION DM, bad glycemic management, and long-term DM are potential risk factors of symptomatic knee OA independent of age and body mass index. Targeting blood glucose, in addition to bodyweight, may be an important avenue for prevention of knee OA.
Collapse
Affiliation(s)
- Jiazhen Zheng
- The Hong Kong University of Science and Technology (Guangzhou), Guangzhou, China, and the Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China
| | - Xihao Huang
- West China Hospital, Sichuan University, Chengdu, China
| | | | | | - Furong Li
- Southern University of Science and Technology, Shenzhen, China
| | - Huamin Liu
- Southern Medical University, Guangzhou, China
| | | | - Rui Zhou
- Southern Medical University, Guangzhou, China
| | - Mengchen Zou
- Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Xianbo Wu
- Southern Medical University, Guangzhou, China
| |
Collapse
|
|
11
|
Cao J, Hua L, Dong L, Wu Z, Xue G. The Value of the Monocyte to High-Density Lipoprotein Cholesterol Ratio in Assessing the Severity of Knee Osteoarthritis: A Retrospective Single Center Cohort Study. J Inflamm Res 2023; 16:595-604. [PMID: 36818193 PMCID: PMC9930583 DOI: 10.2147/jir.s395229] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2022] [Accepted: 02/03/2023] [Indexed: 02/13/2023] Open
Abstract
Background Inflammatory responses and metabolic abnormalities play essential roles in the pathophysiology of osteoarthritis (OA). Our study aimed to evaluate the association between monocyte-to-high density lipoprotein-cholesterol ratio (MHR) and OA and compared it with other systemic inflammatory markers. Methods This study recruited 323 OA cases and age- and sex-matched 283 control participants during the same period. Demographic, clinical, and imaging data and laboratory indicators were obtained from participants' records. Systemic inflammatory markers were calculated for both cohorts. The diagnostic effectiveness of each index for distinguishing patients with OA was analyzed using receiver operating characteristic (ROC) curves. Spearman's method and ordered logistic regression were used to analyze the association between each indicator and Kellgren and Lawrence (KL) grade. Results MHR was significantly higher (0.38±0.18 vs 0.25±0.07, p < 0.0001) in OA patients than healthy controls. MHR had the largest area under the ROC curve for predicting OA. Analysis of ordered logistic regression indicated that MHR was a risk factor for OA radiological severity. Spearman correlation analysis indicated that MHR significantly correlates with the KL grade. Moreover, MHR was significantly higher in early stage patients than in healthy controls. Conclusion These results suggest that an elevated MHR could reflect knee OA severity and might be a useful marker for diagnosis and monitoring of OA.
Collapse
Affiliation(s)
- Jun Cao
- Department of Biochemistry and Molecular Biology, School of Medicine, Jiujiang University, Jiujiang, People’s Republic of China
| | - Lin Hua
- Department of Clinical Laboratory, Jiujiang NO.1 People’s Hospital, Jiujiang, People’s Republic of China
| | - Liang Dong
- Department of Rheumatology, Jiujiang NO.1 People’s Hospital, Jiujiang, People’s Republic of China
| | - Zhouhuan Wu
- Department of Pharmacology, School of Medicine, Jiujiang University, Jiujiang, People’s Republic of China
| | - Guohui Xue
- Department of Clinical Laboratory, Jiujiang NO.1 People’s Hospital, Jiujiang, People’s Republic of China,Correspondence: Guohui Xue, Email
| |
Collapse
|
|
12
|
Batushansky A, Zhu S, Komaravolu RK, South S, Mehta-D'souza P, Griffin TM. Fundamentals of OA. An initiative of Osteoarthritis and Cartilage. Obesity and metabolic factors in OA. Osteoarthritis Cartilage 2022; 30:501-515. [PMID: 34537381 PMCID: PMC8926936 DOI: 10.1016/j.joca.2021.06.013] [Citation(s) in RCA: 67] [Impact Index Per Article: 22.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/08/2021] [Revised: 05/14/2021] [Accepted: 06/07/2021] [Indexed: 02/02/2023]
Abstract
OBJECTIVE Obesity was once considered a risk factor for knee osteoarthritis (OA) primarily for biomechanical reasons. Here we provide an additional perspective by discussing how obesity also increases OA risk by altering metabolism and inflammation. DESIGN This narrative review is presented in four sections: 1) metabolic syndrome and OA, 2) metabolic biomarkers of OA, 3) evidence for dysregulated chondrocyte metabolism in OA, and 4) metabolic inflammation: joint tissue mediators and mechanisms. RESULTS Metabolic syndrome and its components are strongly associated with OA. However, evidence for a causal relationship is context dependent, varying by joint, gender, diagnostic criteria, and demographics, with additional environmental and genetic interactions yet to be fully defined. Importantly, some aspects of the etiology of obesity-induced OA appear to be distinct between men and women, especially regarding the role of adipose tissue. Metabolomic analyses of serum and synovial fluid have identified potential diagnostic biomarkers of knee OA and prognostic biomarkers of disease progression. Connecting these biomarkers to cellular pathophysiology will require future in vivo studies of joint tissue metabolism. Such studies will help reveal when a metabolic process or a metabolite itself is a causal factor in disease progression. Current evidence points towards impaired chondrocyte metabolic homeostasis and metabolic-immune dysregulation as likely factors connecting obesity to the increased risk of OA. CONCLUSIONS A deeper understanding of how obesity alters metabolic and inflammatory pathways in synovial joint tissues is expected to provide new therapeutic targets and an improved definition of "metabolic" and "obesity" OA phenotypes.
Collapse
Affiliation(s)
- A Batushansky
- Aging and Metabolism Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, 73104, USA.
| | - S Zhu
- Department of Biomedical Sciences, Ohio Musculoskeletal and Neurological Institute (OMNI), Ohio University, Athens, OH, 45701, USA.
| | - R K Komaravolu
- Aging and Metabolism Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, 73104, USA.
| | - S South
- Aging and Metabolism Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, 73104, USA.
| | - P Mehta-D'souza
- Aging and Metabolism Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, 73104, USA.
| | - T M Griffin
- Aging and Metabolism Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, 73104, USA; Reynolds Oklahoma Center on Aging, Department of Biochemistry and Molecular Biology, Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, USA; Veterans Affairs Medical Center, Oklahoma City, OK, 73104, USA.
| |
Collapse
|
|
13
|
Go DJ, Kim DH, Guermazi A, Crema MD, Hunter DJ, Hwang HS, Kim HA. Metabolic obesity and the risk of knee osteoarthritis progression in elderly community residents: A 3-year longitudinal cohort study. Int J Rheum Dis 2021; 25:192-200. [PMID: 34877797 DOI: 10.1111/1756-185x.14255] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2021] [Revised: 10/29/2021] [Accepted: 11/22/2021] [Indexed: 01/03/2023]
Abstract
OBJECTIVE Metabolic syndrome is a major health problem worldwide associated with obesity, thus drawing attention to its relation to osteoarthritis (OA). However, it is still uncertain whether metabolic syndrome or body fat distribution is associated with knee OA. The aim of this longitudinal study was to elucidate the association between metabolic obesity and adverse structural changes of knee OA assessed by magnetic resonance imaging (MRI). METHODS Participants were recruited from the Hallym Aging Study cohort in Korea. Knee MRI scans, along with dual-energy X-ray absorptiometry, were assessed in 226 participants at baseline and after 3 years. The structural progression in the tibiofemoral joint was evaluated using the semi-quantitative Whole-Organ MRI Score (WORMS) for cartilage morphology and bone marrow lesions (BML). Logistic regression with generalized estimating equation was performed for associations of metabolic risk factors with worsening of WORMS scores at the subregional level. RESULTS In the medial compartment, fat mass in women was associated with cartilage loss, but the statistical significance disappeared after adjusting for body mass index. Metabolic syndrome and each of its components were not associated with cartilage loss or increase of BML. On the other hand, the interaction effects of metabolic syndrome on the association between obesity and knee OA progression were not significant. CONCLUSION In this cohort, metabolic effects of obesity on knee cartilage damage and BML were not demonstrated. Further large-scale studies are required to prove the causal relationship between metabolic obesity and knee OA.
Collapse
Affiliation(s)
- Dong Jin Go
- Division of Rheumatology, Department of Internal Medicine, Hallym University Kangnam Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Korea.,Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, and College of Medicine, Medical Research Institute, Seoul National University, Seoul, Korea
| | - Dong Hyun Kim
- Department of Social and Preventive Medicine, Hallym Research Institute of Clinical Epidemiology, Hallym University, Chuncheon, Korea
| | - Ali Guermazi
- Department of Radiology, Boston University School of Medicine, Boston, Massachusetts, USA
| | - Michel Daoud Crema
- Department of Radiology, Boston University School of Medicine, Boston, Massachusetts, USA
| | - David J Hunter
- Department of Rheumatology, Royal North Shore Hospital and Institute of Bone and Joint Research, University of Sydney, Sydney, New South Wales, Australia
| | - Hyun Sook Hwang
- Division of Rheumatology, Department of Internal Medicine, Hallym University Sacred Heart Hospital, Anyang, Korea.,Institute for Skeletal Aging, Hallym University, Chuncheon, Korea
| | - Hyun Ah Kim
- Division of Rheumatology, Department of Internal Medicine, Hallym University Sacred Heart Hospital, Anyang, Korea.,Institute for Skeletal Aging, Hallym University, Chuncheon, Korea
| |
Collapse
|
|
14
|
Zhang K, Ji Y, Dai H, Khan AA, Zhou Y, Chen R, Jiang Y, Gui J. High-Density Lipoprotein Cholesterol and Apolipoprotein A1 in Synovial Fluid: Potential Predictors of Disease Severity of Primary Knee Osteoarthritis. Cartilage 2021; 13:1465S-1473S. [PMID: 33870758 PMCID: PMC8808802 DOI: 10.1177/19476035211007919] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
OBJECTIVES The aim of this study was to detect levels of common lipid species in serum and synovial fluid (SF) of primary knee osteoarthritis (OA) patients and investigate their correlations with disease severity. MATERIALS AND METHODS The study enrolled 184 OA patients receiving arthroscopic debridement or total knee arthroplasty and 180 healthy controls between April 2012 and March 2018. Total triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein A1 (ApoA1), and apolipoprotein B (ApoB) levels were analyzed in serum and SF of OA patients, and in serum of healthy individuals. The Noyes rating criteria, Kellgren-Lawrence (KL) grading system, and Western Ontario McMaster University Osteoarthritis Index (WOMAC) scores were, respectively, used to assess cartilage damage, radiographic severity, and symptomatic severity of OA. RESULTS No significant differences were found in serum TG and ApoB levels between the 2 groups, while OA patients had higher TC and LDL-C levels and lower HDL-C and ApoA1 levels (P < 0.05). Pearson correlation analysis revealed SF HDL-C and ApoA1 levels were negatively correlated with cartilage damage scores, KL grades as well as WOMAC scores (P < 0.05), which were still significant after adjusting for confounding factors (P < 0.05). Receiver operating characteristic curve analysis revealed SF HDL-C (area under the curve [AUC]: 0.816) and ApoA1 (AUC: 0.793) were also good predictors of advanced-stage OA (P < 0.001). CONCLUSION SF HDL-C and ApoA1 levels were negatively correlated with cartilage damage, radiographic severity, and symptomatic severity of primary knee OA, emerging as potential biomarkers for radiographic advanced-stage OA, which may serve as predictors of disease severity.
Collapse
Affiliation(s)
- Kaibin Zhang
- Department of Orthopaedics, Nanjing
First Hospital, Nanjing Medical University, Nanjing, Jiangsu Province, People’s
Republic of China
| | - Yisheng Ji
- The First Clinical College, Nanjing
Medical University, Nanjing, Jiangsu Province, People’s Republic of China
| | - Hanhao Dai
- Department of Orthopedics, Shengli
Clinical Medical College of Fujian Medical University, Fujian Medical University,
Fuzhou, Fujian Province, People’s Republic of China
| | - Abdul Aleem Khan
- Department of Orthopaedics, Nanjing
First Hospital, Nanjing Medical University, Nanjing, Jiangsu Province, People’s
Republic of China
| | - Yang Zhou
- Department of Orthopaedics, Nanjing
First Hospital, Nanjing Medical University, Nanjing, Jiangsu Province, People’s
Republic of China
| | - Ran Chen
- Department of Orthopaedics, Nanjing
First Hospital, Nanjing Medical University, Nanjing, Jiangsu Province, People’s
Republic of China
| | - Yiqiu Jiang
- Department of Orthopaedics, Nanjing
First Hospital, Nanjing Medical University, Nanjing, Jiangsu Province, People’s
Republic of China
| | - Jianchao Gui
- Department of Orthopaedics, Nanjing
First Hospital, Nanjing Medical University, Nanjing, Jiangsu Province, People’s
Republic of China,Jianchao Gui, Department of Orthopaedics,
Nanjing First Hospital, Nanjing Medical University, ChangLe Road 68, Nanjing,
Jiangsu Province 210000, People’s Republic of China.
| |
Collapse
|
|
15
|
Lv Z, Yang YX, Li J, Fei Y, Guo H, Sun Z, Lu J, Xu X, Jiang Q, Ikegawa S, Shi D. Molecular Classification of Knee Osteoarthritis. Front Cell Dev Biol 2021; 9:725568. [PMID: 34513847 PMCID: PMC8429960 DOI: 10.3389/fcell.2021.725568] [Citation(s) in RCA: 50] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2021] [Accepted: 08/09/2021] [Indexed: 01/15/2023] Open
Abstract
Knee osteoarthritis (KOA) is the most common form of joint degeneration with increasing prevalence and incidence in recent decades. KOA is a molecular disorder characterized by the interplay of numerous molecules, a considerable number of which can be detected in body fluids, including synovial fluid, urine, and blood. However, the current diagnosis and treatment of KOA mainly rely on clinical and imaging manifestations, neglecting its molecular pathophysiology. The mismatch between participants' molecular characteristics and drug therapeutic mechanisms might explain the failure of some disease-modifying drugs in clinical trials. Hence, according to the temporal alteration of representative molecules, we propose a novel molecular classification of KOA divided into pre-KOA, early KOA, progressive KOA, and end-stage KOA. Then, progressive KOA is furtherly divided into four subtypes as cartilage degradation-driven, bone remodeling-driven, inflammation-driven, and pain-driven subtype, based on the major pathophysiology in patient clusters. Multiple clinical findings of representatively investigated molecules in recent years will be reviewed and categorized. This molecular classification allows for the prediction of high-risk KOA individuals, the diagnosis of early KOA patients, the assessment of therapeutic efficacy, and in particular, the selection of homogenous patients who may benefit most from the appropriate therapeutic agents.
Collapse
Affiliation(s)
- Zhongyang Lv
- State Key Laboratory of Pharmaceutical Biotechnology, Division of Sports Medicine and Adult Reconstructive Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China
| | - Yannick Xiaofan Yang
- State Key Laboratory of Pharmaceutical Biotechnology, Division of Sports Medicine and Adult Reconstructive Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China
| | - Jiawei Li
- State Key Laboratory of Pharmaceutical Biotechnology, Division of Sports Medicine and Adult Reconstructive Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China
| | - Yuxiang Fei
- State Key Laboratory of Pharmaceutical Biotechnology, Division of Sports Medicine and Adult Reconstructive Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China
| | - Hu Guo
- State Key Laboratory of Pharmaceutical Biotechnology, Division of Sports Medicine and Adult Reconstructive Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China
| | - Ziying Sun
- State Key Laboratory of Pharmaceutical Biotechnology, Division of Sports Medicine and Adult Reconstructive Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China
| | - Jun Lu
- State Key Laboratory of Pharmaceutical Biotechnology, Division of Sports Medicine and Adult Reconstructive Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China
| | - Xingquan Xu
- State Key Laboratory of Pharmaceutical Biotechnology, Division of Sports Medicine and Adult Reconstructive Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China
| | - Qing Jiang
- State Key Laboratory of Pharmaceutical Biotechnology, Division of Sports Medicine and Adult Reconstructive Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China
| | - Shiro Ikegawa
- Laboratory for Bone and Joint Diseases, RIKEN Center for Integrative Medical Science (IMS, RIKEN), Tokyo, Japan
| | - Dongquan Shi
- State Key Laboratory of Pharmaceutical Biotechnology, Division of Sports Medicine and Adult Reconstructive Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China
| |
Collapse
|
|
16
|
Khor A, Ma CA, Hong C, Hui LLY, Leung YY. Diabetes mellitus is not a risk factor for osteoarthritis. RMD Open 2021; 6:rmdopen-2019-001030. [PMID: 32060073 PMCID: PMC7046958 DOI: 10.1136/rmdopen-2019-001030] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2019] [Revised: 12/18/2019] [Accepted: 12/21/2019] [Indexed: 12/22/2022] Open
Abstract
BACKGROUND Association between diabetes mellitus (DM) and risk of osteoarthritis (OA) can be confounded by body mass index (BMI), a strong risk factor for both conditions. We evaluate the association between DM or hyperglycaemia with OA using systematic review and meta-analysis. METHODS We searched PubMed and Web of Science databases in English for studies that gave information on the association between DM and OA. Two meta-analysis models were conducted to address: (1) risk of DM comparing subjects with and without OA and (2) risk of OA comparing subjects with and without DM. As far as available, risk estimates that adjusted for BMI were used. RESULTS 31 studies with a pooled population size of 295 100 subjects were reviewed. 16 and 15 studies reported positive associations and null/ negative associations between DM and OA. 68.8% of positive studies had adjusted for BMI, compared with 93.3% of null/negative studies. In meta-analysis model 1, there was an increase prevalence of DM in subjects with OA compared with those without (OR 1.56, 95% CI 1.28 to 1.89). In meta-analysis model 2, there was no increased risk of OA (OR 1.14, 95% CI 0.98 to 1.33) in subjects with DM compared with those without, regardless of gender and OA sites. Comparing subjects with DM to those without, an increased risk of OA was noted in cross-sectional studies, but not in case-control and prospective cohort studies. CONCLUSIONS This meta-analysis does not support DM as an independent risk factor for OA. BMI was probably the most important confounding factor.
Collapse
Affiliation(s)
- Andrew Khor
- Rheumatology and Immunology, Singapore General Hospital, Singapore, Singapore
| | | | - Cassandra Hong
- Rheumatology and Immunology, Singapore General Hospital, Singapore, Singapore.,Duke-NUS Medical School, Singapore, Singapore
| | - Laura Li-Yao Hui
- Rheumatology and Immunology, Singapore General Hospital, Singapore, Singapore
| | - Ying Ying Leung
- Rheumatology and Immunology, Singapore General Hospital, Singapore, Singapore .,Duke-NUS Medical School, Singapore, Singapore
| |
Collapse
|
|
17
|
Zaharia OP, Pesta DH, Bobrov P, Kupriyanova Y, Herder C, Karusheva Y, Bódis K, Bönhof GJ, Knitza J, Simon D, Kleyer A, Hwang JH, Müssig K, Ziegler D, Burkart V, Schett G, Roden M, Szendroedi J. Reduced Muscle Strength Is Associated With Insulin Resistance in Type 2 Diabetes Patients With Osteoarthritis. J Clin Endocrinol Metab 2021; 106:1062-1073. [PMID: 33382877 PMCID: PMC7993587 DOI: 10.1210/clinem/dgaa912] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/05/2020] [Indexed: 12/19/2022]
Abstract
CONTEXT Type 2 diabetes is associated with a greater risk for musculoskeletal disorders, yet its impact on joint function remains unclear. OBJECTIVE We hypothesized that patients with type 2 diabetes and osteoarthritis would exhibit musculoskeletal impairment, which would associate with insulin resistance and distinct microRNA profiles. METHODS Participants of the German Diabetes Study with type 2 diabetes (T2D, n = 39) or normal glucose tolerance (CON, n = 27), both with (+OA) or without osteoarthritis (-OA) underwent intravenous glucose tolerance and hyperinsulinemic-euglycemic clamp tests. Musculoskeletal function was assessed by isometric knee extension strength (KES), grip strength, range of motion (ROM), and balance skills, while neural function was measured by nerve conductance velocity (NCV). Arthritis-related symptoms were quantified using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) questionnaire, serum arthritis-related microRNA using quantitative polymerase chain reaction. RESULTS Insulin sensitivity was lower in T2D+OA vs T2D-OA (4.4 ± 2.0 vs 5.7 ± 3.0 mg* kg-1*min-1) and in CON+OA vs CON-OA (8.1 ± 2.0 vs 12.0 ± 2.6 mg*kg-1,*min-1, both P < .05). In T2D+OA, KES and ROM were 60% and 22% lower than in CON+OA, respectively (both P < .05). Insulin sensitivity correlated positively with KES (r = 0.41, P < .05) among T2D, and negatively with symptom severity in CON and T2D (r = -0.60 and r = -0.46, respectively, P < .05). CON+OA and T2D+OA had inferior balance skills than CON-OA, whereas NCV was comparable in T2D+OA and T2D-OA. Expression of arthritis-related microRNAs was upregulated in T2D compared to CON, but downregulated in CON+OA compared to CON-OA (P < .05), and did not differ between T2D+OA and T2D-OA. CONCLUSION Musculoskeletal impairment and osteoarthritis-related symptoms are associated with insulin resistance. Type 2 diabetes can mask changes in arthritis-related microRNA profiles.
Collapse
Affiliation(s)
- Oana Patricia Zaharia
- Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, Düsseldorf, Germany
- German Center for Diabetes Research (DZD), München-Neuherberg, Germany
- Division of Endocrinology and Diabetology, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany
| | - Dominik Hans Pesta
- Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, Düsseldorf, Germany
- German Center for Diabetes Research (DZD), München-Neuherberg, Germany
| | - Pavel Bobrov
- German Center for Diabetes Research (DZD), München-Neuherberg, Germany
- Institute for Biometrics and Epidemiology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, Düsseldorf, Germany
| | - Yuliya Kupriyanova
- Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, Düsseldorf, Germany
- German Center for Diabetes Research (DZD), München-Neuherberg, Germany
| | - Christian Herder
- Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, Düsseldorf, Germany
- German Center for Diabetes Research (DZD), München-Neuherberg, Germany
- Division of Endocrinology and Diabetology, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany
| | - Yanislava Karusheva
- Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, Düsseldorf, Germany
- German Center for Diabetes Research (DZD), München-Neuherberg, Germany
| | - Kálmán Bódis
- Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, Düsseldorf, Germany
- German Center for Diabetes Research (DZD), München-Neuherberg, Germany
- Division of Endocrinology and Diabetology, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany
| | - Gidon Josia Bönhof
- Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, Düsseldorf, Germany
- German Center for Diabetes Research (DZD), München-Neuherberg, Germany
- Division of Endocrinology and Diabetology, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany
| | - Johannes Knitza
- Department of Internal Medicine 3-Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany; Universitätsklinikum Erlangen, Erlangen, Germany
| | - David Simon
- Department of Internal Medicine 3-Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany; Universitätsklinikum Erlangen, Erlangen, Germany
| | - Arnd Kleyer
- Department of Internal Medicine 3-Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany; Universitätsklinikum Erlangen, Erlangen, Germany
| | - Jong-Hee Hwang
- Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, Düsseldorf, Germany
- German Center for Diabetes Research (DZD), München-Neuherberg, Germany
| | - Karsten Müssig
- Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, Düsseldorf, Germany
| | - Dan Ziegler
- Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, Düsseldorf, Germany
- German Center for Diabetes Research (DZD), München-Neuherberg, Germany
- Division of Endocrinology and Diabetology, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany
| | - Volker Burkart
- Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, Düsseldorf, Germany
- German Center for Diabetes Research (DZD), München-Neuherberg, Germany
| | - Georg Schett
- Department of Internal Medicine 3-Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany; Universitätsklinikum Erlangen, Erlangen, Germany
| | - Michael Roden
- Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, Düsseldorf, Germany
- German Center for Diabetes Research (DZD), München-Neuherberg, Germany
- Division of Endocrinology and Diabetology, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany
| | - Julia Szendroedi
- Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, Düsseldorf, Germany
- German Center for Diabetes Research (DZD), München-Neuherberg, Germany
- Division of Endocrinology and Diabetology, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany
- Correspondence: Julia Szendroedi, MD, PhD, German Diabetes Center, Clinical Research Center, c/o Auf`m Hennekamp 65, D-40225 Düsseldorf, Germany.
| |
Collapse
|
|
18
|
Sun AR, Udduttula A, Li J, Liu Y, Ren PG, Zhang P. Cartilage tissue engineering for obesity-induced osteoarthritis: Physiology, challenges, and future prospects. J Orthop Translat 2021; 26:3-15. [PMID: 33437618 PMCID: PMC7773977 DOI: 10.1016/j.jot.2020.07.004] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/10/2020] [Revised: 06/25/2020] [Accepted: 07/21/2020] [Indexed: 12/14/2022] Open
Abstract
UNLABELLED Osteoarthritis (OA) is a multifactorial joint disease with pathological changes that affect whole joint tissue. Obesity is acknowledged as the most influential risk factor for both the initiation and progression of OA in weight-bearing and non-weight-bearing joints. Obesity-induced OA is a newly defined phenotypic group in which chronic low-grade inflammation has a central role. Aside from persistent chronic inflammation, abnormal mechanical loading due to increased body weight on weight-bearing joints is accountable for the initiation and progression of obesity-induced OA. The current therapeutic approaches for OA are still evolving. Tissue-engineering-based strategy for cartilage regeneration is one of the most promising treatment breakthroughs in recent years. However, patients with obesity-induced OA are often excluded from cartilage repair attempts due to the abnormal mechanical demands, altered biomechanical and biochemical activities of cells, persistent chronic inflammation, and other obesity-associated factors. With the alarming increase in the number of obese populations globally, the need for an innovative therapeutic approach that could effectively repair and restore the damaged synovial joints is of significant importance for this sub-population of patients. In this review, we discuss the involvement of the systemic and localized inflammatory response in obesity-induced OA and the impact of altered mechanical loading on pathological changes in the synovial joint. Moreover, we examine the current strategies in cartilage tissue engineering and address the critical challenges of cell-based therapies for OA. Besides, we provide examples of innovative ways and potential strategies to overcome the obstacles in the treatment of obesity-induced OA. THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE Altogether, this review delivers insight into obesity-induced OA and offers future research direction on the creation of tissue engineering-based therapies for obesity-induced OA.
Collapse
Affiliation(s)
- Antonia RuJia Sun
- Center for Translational Medicine Research and Development, Shenzhen Institutes of Advanced Technology, Chinese Academy of Science, Shenzhen, Guangdong, 518055, China
| | - Anjaneyulu Udduttula
- Center for Energy Metabolism and Reproduction, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong, 518055, China
| | - Jian Li
- Center for Translational Medicine Research and Development, Shenzhen Institutes of Advanced Technology, Chinese Academy of Science, Shenzhen, Guangdong, 518055, China
| | - Yanzhi Liu
- Center for Translational Medicine Research and Development, Shenzhen Institutes of Advanced Technology, Chinese Academy of Science, Shenzhen, Guangdong, 518055, China
- Guangdong Key Laboratory for Research and Development of Natural Drugs, Department of Pharmacology, Guangdong Medical University, Zhanjiang, Guangdong, 524023, China
| | - Pei-Gen Ren
- Center for Energy Metabolism and Reproduction, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong, 518055, China
| | - Peng Zhang
- Center for Translational Medicine Research and Development, Shenzhen Institutes of Advanced Technology, Chinese Academy of Science, Shenzhen, Guangdong, 518055, China
- Shenzhen Engineering Research Center for Medical Bioactive Materials, Shenzhen, Guangdong, 518055, China
| |
Collapse
|
|
19
|
Kumar A, Palit P, Thomas S, Gupta G, Ghosh P, Goswami RP, Kumar Maity T, Dutta Choudhury M. Osteoarthritis: Prognosis and emerging therapeutic approach for disease management. Drug Dev Res 2020; 82:49-58. [PMID: 32931079 DOI: 10.1002/ddr.21741] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2020] [Revised: 08/24/2020] [Accepted: 08/25/2020] [Indexed: 12/21/2022]
Abstract
Osteoarthritis (OA), a disorder of joints, is prevalent in older age. The contemporary cure for OA is aimed to confer symptomatic relief, consisting of temporary pain and swelling relief. In this paper, we discuss various modalities responsible for the onset of OA and associated with its severity. Inhibition of chondrocytes receptors such as DDR2, SDF-1, Asporin, and CXCR4 by specific pharmacological inhibitors attenuates OA, a critical step for finding potential disease modifying drugs. We critically analyzed recent OA studies with an emphasis on intermediate target molecules for OA intervention. We also explored some novel and safe treatments for OA by considering disease prognosis crosstalk with cellular signaling pathways.
Collapse
Affiliation(s)
- Amresh Kumar
- Department of Life Sciences and Bioinformatics, Assam University, Silchar, India
| | - Partha Palit
- Department of Pharmaceutical Sciences, Assam University, Silchar, India
| | - Sabu Thomas
- Department of Chemical Sciences, Mahatma Gandhi University, Kottayam, India
| | - Gaurav Gupta
- Department of Immunology, University of Manitoba, Winnipeg, Manitoba, Canada.,Area of Biotechnology and Bioinformatics, NIIT University, Neemrana, Rajasthan, India
| | - Parasar Ghosh
- Department of Rheumatology, Institute of Post Graduate Medical Education &Research, Kolkata, India
| | | | - Tapan Kumar Maity
- Department of Pharmaceutical Technology, Jadavpur University, Kolkata, India
| | | |
Collapse
|
|
20
|
Charen DA, Solomon D, Zubizarreta N, Poeran J, Colvin AC. Examining the Association of Knee Pain with Modifiable Cardiometabolic Risk Factors. Arthritis Care Res (Hoboken) 2020; 73:1777-1783. [PMID: 32799426 DOI: 10.1002/acr.24423] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2020] [Accepted: 08/11/2020] [Indexed: 11/10/2022]
Abstract
OBJECTIVE There is a well-established link between obesity and knee osteoarthritis, and recent research has implicated diabetes as a potential cause of cartilage degeneration. This study uses the National Health and Nutrition Examination Survey (NHANES) database to examine the association between knee pain and various metabolic factors. METHODS A retrospective cross-sectional study of the NHANES database from 1999 to 2004 was performed. The main outcome was any knee pain and bilateral knee pain. Main effects of interest were body mass index (BMI), and hemoglobin A1c (HbA1c). We additionally assessed various patient factors including age, race, poverty, gender and smoking status. Multivariable logistic regression models and interaction terms were analyzed. RESULTS Data on 12,900 patients was included. In the main adjusted analysis, the modifiable risk factors associated with any knee pain were: overweight (OR 0.91; 95% CI 0.85, 0.97), obesity (OR 1.54; 95% CI 1.42, 1.66), glycemic control (OR 1.20; 95% CI 1.03, 1.38), and current smokers (OR 1.15; 95% CI 1.05, 1.27), all p<0.05. These same factors remain significant for bilateral knee pain. Subgroup analysis showed patients under 65 years old have a 5% increase in risk of any knee pain as their body mass index increases, but patients 65 years and older have a 10% increase in risk. CONCLUSION This study confirms the association of knee pain with increased weight, glycemic control, current smoking and age. Most of these risk factors can be modified in patients with knee pain and should be discussed when providing conservative treatment options.
Collapse
Affiliation(s)
- Daniel A Charen
- Leni and Peter May Department of Orthopaedic Surgery, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - David Solomon
- Department of Orthopedic Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Nicole Zubizarreta
- Leni and Peter May Department of Orthopaedic Surgery, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Jashvant Poeran
- Leni and Peter May Department of Orthopaedic Surgery, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Alexis C Colvin
- Leni and Peter May Department of Orthopaedic Surgery, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| |
Collapse
|
|
21
|
Gao YH, Zhao CW, Liu B, Dong N, Ding L, Li YR, Liu JG, Feng W, Qi X, Jin XH. An update on the association between metabolic syndrome and osteoarthritis and on the potential role of leptin in osteoarthritis. Cytokine 2020; 129:155043. [PMID: 32078923 DOI: 10.1016/j.cyto.2020.155043] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2019] [Revised: 01/22/2020] [Accepted: 02/11/2020] [Indexed: 12/23/2022]
Abstract
Metabolic syndrome (MetS) has been associated with osteoarthritis (OA). Leptin, which is one of the markers of MetS, has been associated with OA pathophysiology. This study aimed to provide an update on the association between MetS and OA and on the potential role of leptin in OA. In this review, we summarized the current knowledge of the association between MetS and OA and updated the evidence on the potential role of leptin in OA. Clinical studies have investigated the epidemiologic association between MetS or its components and OA. Results suggested strong epidemiologic associations between MetS and OA, especially in the Asian population. Animal studies also indicated that metabolic dysregulation may lead to OA pathogenesis. The systemic role of MetS in OA pathophysiology is associated with obesity-related inflammation, the beneficial role of n-3 polyunsaturated fatty acids and deleterious role of cholesterol, physical inactivity, hypertension-induced subchondral ischemia, dyslipidemia-induced ectopic lipid deposition in chondrocytes, hyperglycemia-induced local effects of oxidative stress and advanced glycation end-products, low-grade systemic inflammation, and obesity-related adipokines by inducing the expression of proinflammtory factors. Leptin levels in serum/plasma and synovial fluid were associated with joint pain, radiographic progression, bone formation biomarkers, cartilage volume, knee OA incidence, and total joint arthroplasty in OA patients. Elevated leptin expression and increased effect of leptin on infrapatellar fat pad, synovium, articular cartilage, and bone were also involved in the pathogenesis of OA. Current knowledge indicates a convincing epidemiologic association between MetS and OA, especially in the Asian population. Animal studies have also shown that metabolic dysregulation may lead to OA pathogenesis. Accumulating evidence suggests that leptin may play a potential role in OA pathogenesis. Therefore, leptin and its receptor may be an emerging target for intervention in metabolic-associated OA.
Collapse
Affiliation(s)
- Yu-Hang Gao
- Department of Orthopaedic Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, China
| | - Cheng-Wu Zhao
- Department of Sports Medicine, The First Hospital of Jilin University, Changchun, Jilin 130021, China
| | - Bo Liu
- Department of Ultrasound, The First Hospital of Jilin University, Changchun, Jilin 130021, China
| | - Ning Dong
- Department of Pediatric Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, China
| | - Lu Ding
- Department of Orthopaedic Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, China
| | - Ye-Ran Li
- Department of Orthopaedic Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, China
| | - Jian-Guo Liu
- Department of Orthopaedic Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, China
| | - Wei Feng
- Department of Orthopaedic Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, China
| | - Xin Qi
- Department of Orthopaedic Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, China.
| | - Xian-Hua Jin
- Department of Dermatology, The Second Hospital of Jilin University, Changchun, Jilin 130022, China.
| |
Collapse
|
|
22
|
Sansone V, Applefield RC, De Luca P, Pecoraro V, Gianola S, Pascale W, Pascale V. Does a high-fat diet affect the development and progression of osteoarthritis in mice?: A systematic review. Bone Joint Res 2020; 8:582-592. [PMID: 31934329 PMCID: PMC6946912 DOI: 10.1302/2046-3758.812.bjr-2019-0038.r1] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/09/2022] Open
Abstract
Aims The aim of this study was to systematically review the literature for evidence of the effect of a high-fat diet (HFD) on the onset or progression of osteoarthritis (OA) in mice. Methods A literature search was performed in PubMed, Embase, Web of Science, and Scopus to find all studies on mice investigating the effects of HFD or Western-type diet on OA when compared with a control diet (CD). The primary outcome was the determination of cartilage loss and alteration. Secondary outcomes regarding local and systemic levels of proteins involved in inflammatory processes or cartilage metabolism were also examined when reported. Results In total, 14 publications met our inclusion criteria and were included in our review. Our meta-analysis showed that, when measured by the modified Mankin Histological-Histochemical Grading System, there was a significantly higher rate of OA in mice fed a HFD than in mice on a CD (standardized mean difference (SMD) 1.27, 95% confidence interval (CI) 0.63 to 1.91). Using the Osteoarthritis Research Society International (OARSI) score, there was a trend towards HFD causing OA (SMD 0.78, 95% CI -0.04 to 1.61). In terms of OA progression, a HFD consistently worsened the progression of surgically induced OA when compared with a CD. Finally, numerous inflammatory cytokines such as tumour necrosis factor alpha (TNF-α), interleukin (IL)-1β, and leptin, among others, were found to be altered by a HFD. Conclusion A HFD seems to induce or exacerbate the progression of OA in mice. The metabolic changes and systemic inflammation brought about by a HFD appear to be key players in the onset and progression of OA. Cite this article:Bone Joint Res 2019;8:582–592.
Collapse
Affiliation(s)
- Valerio Sansone
- Department of Orthopaedics, Universitá degli Studi di Milano and IRCCS Istituto Ortopedico Galeazzi, Milan, Italy
| | | | | | - Valentina Pecoraro
- Department of Laboratory Medicine, Ospedale Civile Sant'Agostino Estense di Baggiovra, Baggiovara, Italy
| | | | | | - Valerio Pascale
- Department of Orthopaedics, Universitá degli Studi di Milano and IRCCS Istituto Ortopedico Galeazzi, Milan, Italy
| |
Collapse
|
|
23
|
Dell'Isola A, Vinblad J, Lohmander S, Svensson AM, Turkiewicz A, Franzén S, Nauclér E, W-Dahl A, Abbott A, Dahlberg L, Rolfson O, Englund M. Understanding the role of diabetes in the osteoarthritis disease and treatment process: a study protocol for the Swedish Osteoarthritis and Diabetes (SOAD) cohort. BMJ Open 2019; 9:e032923. [PMID: 31852705 PMCID: PMC6937096 DOI: 10.1136/bmjopen-2019-032923] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/12/2019] [Revised: 11/06/2019] [Accepted: 11/27/2019] [Indexed: 12/04/2022] Open
Abstract
INTRODUCTION Osteoarthritis (OA) is the most common form of arthritis and a leading cause of disability worldwide. Metabolic comorbidities such as type II diabetes occur with a higher rate in people with OA than in the general population. Several factors including obesity, hyperglycaemia toxicity and physical inactivity have been suggested as potential links between diabetes and OA, and have been shown to negatively impact patients' health and quality of life. However, little is known on the role of diabetes in determining the outcome of non-surgical and surgical management of OA, and at the same time, how different OA interventions may affect diabetes control. Thus, the overall aim of this project is to explore (1) the impact of diabetes on the outcome of non-surgical and surgical OA treatments and (2) the impact of non-surgical and surgical OA treatments on diabetes control. METHODS AND ANALYSIS The study cohort is based on prospectively ascertained register data on a national level in Sweden. Data from OA patients who received a first-line non-surgical intervention and are registered in the National Quality Register for Better Management of Patients with Osteoarthritis will be merged with data from the Swedish Knee and Hip Arthroplasty Registers and the National Diabetes Register. Additional variables regarding patients' use of prescribed drugs, comorbidities, socioeconomic status and cause of death will be obtained through other national health and population data registers. The linkage will be performed on an individual level using unique personal identity numbers. ETHICS AND DISSEMINATION This study received ethical approval (2019-02570) from the Swedish Ethical Review Authority. Results from this cohort will be submitted to peer-reviewed scientific journals and reported at the leading national and international meetings in the field.
Collapse
Affiliation(s)
- Andrea Dell'Isola
- Faculty of Medicine, Department of Clinical Sciences, Orthopedics, Lunds University, Lund, Sweden
- Faculty of medicine, Department of Clinical Sciences, Orthopedics, Clinical Epidemiology Unit, Lund University, Lund, Sverige, Sweden
| | - Johanna Vinblad
- Centre of Registers Västra Götaland, The Swedish Hip Arthroplasty Register, Goteborg, Sweden
- Department of Orthopaedics, Sahlgrenska Academy, University of Gothenburg, Institute of Clinical Sciences, Gothenburg, Sweden
| | - Stefan Lohmander
- Faculty of Medicine, Department of Clinical Sciences, Orthopedics, Lunds University, Lund, Sweden
| | - Ann-Marie Svensson
- National Diabetes Register, Centre of Registers in Region Västra Götaland, Goteborg, Sweden
- Department of Molecular and Clinical Medicine, University of Gothenburg, Goteborg, Sweden
| | - Aleksandra Turkiewicz
- Faculty of medicine, Department of Clinical Sciences, Orthopedics, Clinical Epidemiology Unit, Lund University, Lund, Sverige, Sweden
| | - Stefan Franzén
- National Diabetes Register, Centre of Registers Västra Götaland, Gothenburg, Sweden
- Health Metrics Unit, Sahlgrenska Academy, University of Gothenburg, Goteborg, Sweden
| | - Emma Nauclér
- Centre of Registers Västra Götaland, The Swedish Hip Arthroplasty Register, Goteborg, Sweden
| | - A W-Dahl
- Department of Clinical Sciences, Lund University, Lund, Sverige, Sweden
- The Swedish Knee Arthroplasty Register, Lund, Sweden
| | - Allan Abbott
- Department of Medical and Health Sciences (IMH), division of physiotherapy, Faculty of Medicine and Health Sciences, Linkoping University, Linköping, Sweden
| | - L Dahlberg
- Faculty of Medicine, Department of Clinical Sciences, Orthopedics, Lunds University, Lund, Sweden
| | - Ola Rolfson
- Centre of Registers Västra Götaland, The Swedish Hip Arthroplasty Register, Goteborg, Sweden
- Department of Orthopaedics, Sahlgrenska Academy, University of Gothenburg, Institute of Clinical Sciences, Gothenburg, Sweden
| | - Martin Englund
- Faculty of medicine, Department of Clinical Sciences, Orthopedics, Clinical Epidemiology Unit, Lund University, Lund, Sverige, Sweden
| |
Collapse
|
|
24
|
Kroon FPB, Veenbrink AI, de Mutsert R, Visser AW, van Dijk KW, le Cessie S, Rosendaal FR, Kloppenburg M. The role of leptin and adiponectin as mediators in the relationship between adiposity and hand and knee osteoarthritis. Osteoarthritis Cartilage 2019; 27:1761-1767. [PMID: 31450004 DOI: 10.1016/j.joca.2019.08.003] [Citation(s) in RCA: 50] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/02/2019] [Revised: 08/06/2019] [Accepted: 08/12/2019] [Indexed: 02/07/2023]
Abstract
OBJECTIVES To investigate associations of leptin and adiponectin levels with knee and hand osteoarthritis, and explore whether these mediate the association between adiposity and osteoarthritis. METHODS This is a cross-sectional analysis of baseline data from the population-based Netherlands Epidemiology of Obesity study. Adiposity was assessed with body mass index (BMI) and percentage total body fat (%TBF). Osteoarthritis, defined as hand or knee osteoarthritis, was determined using American College of Rheumatology criteria. Fasting serum adipokine levels were measured using immunoassays. Associations between adiposity and osteoarthritis were examined with logistic regression, adjusted for age, sex, ethnicity and education, and additionally for leptin and adiponectin as potential mediators. RESULTS In 6408 participants (56% women, median age 56 years), prevalence of osteoarthritis was 22% (10% isolated knee and 8% isolated hand osteoarthritis). Leptin levels were positively associated with osteoarthritis, while adiponectin levels were not. Leptin partially mediated the association of adiposity with osteoarthritis (OR 1.40 (95%CI 1.30; 1.52) attenuated to 1.38 (1.24; 1.54) per 5 units BMI and OR 1.25 (1.17; 1.35) to 1.20 (1.10; 1.32) per 5 units %TBF, representing 4% and 17% mediation, respectively). Larger proportion mediation by leptin was found in knee (13%/27%) than in hand osteoarthritis (9%/18%). Sex-stratified analyses generally showed stronger associations between adiposity, leptin and osteoarthritis in women than in men. CONCLUSIONS Serum leptin levels were associated with osteoarthritis, and partially mediated the association between adiposity and osteoarthritis, while adiponectin levels were not associated with osteoarthritis. These findings provide evidence for systemic effects of adipose tissue in osteoarthritis.
Collapse
Affiliation(s)
- F P B Kroon
- Department of Rheumatology, Leiden University Medical Centre (LUMC), Leiden, the Netherlands.
| | - A I Veenbrink
- Department of Internal Medicine, Medisch Spectrum Twente, the Netherlands
| | - R de Mutsert
- Department of Clinical Epidemiology, LUMC, Leiden, the Netherlands
| | - A W Visser
- Department of Rheumatology, Leiden University Medical Centre (LUMC), Leiden, the Netherlands
| | - K W van Dijk
- Department of Internal Medicine, LUMC, Leiden, the Netherlands; Department of Human Genetics, LUMC, Leiden, the Netherlands
| | - S le Cessie
- Department of Clinical Epidemiology, LUMC, Leiden, the Netherlands; Department of Biomedical Data Sciences, LUMC, Leiden, the Netherlands
| | - F R Rosendaal
- Department of Clinical Epidemiology, LUMC, Leiden, the Netherlands
| | - M Kloppenburg
- Department of Rheumatology, Leiden University Medical Centre (LUMC), Leiden, the Netherlands; Department of Clinical Epidemiology, LUMC, Leiden, the Netherlands
| |
Collapse
|
|
25
|
Park CY. Vitamin D in the Prevention and Treatment of Osteoarthritis: From Clinical Interventions to Cellular Evidence. Nutrients 2019; 11:E243. [PMID: 30678273 PMCID: PMC6413222 DOI: 10.3390/nu11020243] [Citation(s) in RCA: 30] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2018] [Revised: 01/03/2019] [Accepted: 01/06/2019] [Indexed: 12/11/2022] Open
Abstract
Older adults are recommended vitamin D to prevent fractures. Though this population is also at risk of osteoarthritis (OA), the effect of vitamin D on OA is unclear and may differ by disease state. The relationship between vitamin D and OA during OA initiation and progression were considered in this narrative review of in vivo and in vitro studies. Regarding OA initiation in humans, the small number of published observational studies suggest a lack of association between induction of OA and vitamin D status. Most randomized controlled trials were performed in White OA patients with relatively high vitamin D status (>50 nmol/L). These studies found no benefit of vitamin D supplementation on OA progression. However, subset analyses and one randomized controlled pilot trial indicated that vitamin D supplementation may alleviate joint pain in OA patients with low vitamin D status (<50 nmol/L). As the etiology of OA is recently being more fully uncovered, better animal and cell models are needed. According to currently available clinical results, evidence is lacking to set a vitamin D level to prevent OA, and increasing vitamin D status above 50 nmol/L does not seem to benefit OA patients.
Collapse
|
|
26
|
Murata K, Uchida K, Takano S, Shoji S, Iwase D, Inoue G, Aikawa J, Yokozeki Y, Sekiguchi H, Takaso M. Osteoarthritis patients with high haemoglobin A1c have increased Toll-like receptor 4 and matrix metalloprotease-13 expression in the synovium. Diabetes Metab Syndr Obes 2019; 12:1151-1159. [PMID: 31406471 PMCID: PMC6642645 DOI: 10.2147/dmso.s209677] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/22/2019] [Accepted: 07/04/2019] [Indexed: 12/22/2022] Open
Abstract
PURPOSE While research has identified diabetes mellitus (DM) as a risk factor for knee osteoarthritis (KOA), the underlying mechanisms are not fully understood. Studies suggest that Toll-like receptor 4 (TLR4) expression is elevated in osteoarthritic lesions of OA patients and in target tissues of insulin resistance such as adipose tissue and skeletal muscle in patients with DM. TLR4 is associated with inflammation and catabolic response via regulation of matrix metalloproteases (MMPs). We hypothesized that TLR4 and MMP expression may be increased in the synovial tissue (SYN) of KOA patients with diabetic pathology. We therefore investigated TLR and MMP expression in the SYN of KOA patients with and without high haemoglobin A1c concentrations. PATIENTS AND METHODS A total of 171 patients radiographically diagnosed with KOA were grouped based on their HbA1c concentration (HbA1c ≥6.5 and HbA1c <6.5). We used real-time polymerase chain reaction to compare the expression of TLRs (TLR2, TLR4) and MMPs (MMP2, MMP3, MMP9 and MMP13) in patients' SYN between the two groups. MMP13 regulation by the TLR4 ligand, lipopolysaccharide (LPS), in SYN cells was examined in culture by stimulating SYN cells with LPS or vehicle (culture medium) for 24 h. RESULTS The expression of TLR4 and MMP13 in the HbA1c ≥6.5 group was significantly elevated compared to that in the HbA1c <6.5 group. In contrast, TLR2, MMP2, MMP3 and MMP9 expression levels were similar between the groups. MMP13 mRNA and MMP13 protein levels in SYN cells were significantly higher following stimulation with LPS compared to vehicle. CONCLUSIONS TLR4 and MMP13 expression were elevated in the synovium of osteoarthritis patients with high HbA1c concentrations. Our results may provide insight into the pathology of OA patients with DM.
Collapse
Affiliation(s)
- Kosuke Murata
- Department of Orthopedic Surgery, Kitasato University School of Medicine, Sagamihara City, Kanagawa252-0374, Japan
| | - Kentaro Uchida
- Department of Orthopedic Surgery, Kitasato University School of Medicine, Sagamihara City, Kanagawa252-0374, Japan
- Correspondence: Kentaro UchidaDepartment of Orthopedic Surgery, Kitasato University School of Medicine, 1-15-1 Minami-ku Kitasato, Sagamihara City, Kanagawa252-0374, JapanTel/Fax +81 042 778 9217 Email
| | - Shotaro Takano
- Department of Orthopedic Surgery, Kitasato University School of Medicine, Sagamihara City, Kanagawa252-0374, Japan
| | - Shintaro Shoji
- Department of Orthopedic Surgery, Kitasato University School of Medicine, Sagamihara City, Kanagawa252-0374, Japan
| | - Dai Iwase
- Department of Orthopedic Surgery, Kitasato University School of Medicine, Sagamihara City, Kanagawa252-0374, Japan
| | - Gen Inoue
- Department of Orthopedic Surgery, Kitasato University School of Medicine, Sagamihara City, Kanagawa252-0374, Japan
| | - Jun Aikawa
- Department of Orthopedic Surgery, Kitasato University School of Medicine, Sagamihara City, Kanagawa252-0374, Japan
| | - Yuji Yokozeki
- Department of Orthopedic Surgery, Kitasato University School of Medicine, Sagamihara City, Kanagawa252-0374, Japan
| | - Hiroyuki Sekiguchi
- Shonan University of Medical Sciences Research Institute, Chigasaki City, Kanagawa253-0083, Japan
| | - Masashi Takaso
- Department of Orthopedic Surgery, Kitasato University School of Medicine, Sagamihara City, Kanagawa252-0374, Japan
| |
Collapse
|
|
27
|
Castano Betancourt MC, Morais CL, Vannucci Nunes Lipay M, Aragão J, de Azevedo e Souza Munhoz M, Gomes Machado E, Marchi E. Gender differences in the effect of diabetes mellitus and its treatment on osteoarthritic pain. BMJ Open Diabetes Res Care 2019; 7:e000736. [PMID: 31798897 PMCID: PMC6861009 DOI: 10.1136/bmjdrc-2019-000736] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/04/2019] [Revised: 09/13/2019] [Accepted: 10/09/2019] [Indexed: 11/06/2022] Open
Abstract
OBJECTIVE (1) To investigate differences in pain severity and its distribution between patients with and without diabetes mellitus (DM) in a population with advanced osteoarthritis (OA). (2) To explore the role of medication used for diabetes in these associations. RESEARCH DESIGN AND METHODS This is a hospital-based cohort study of patients with advanced OA requiring total joint arthroplasty. Interviews and electronic records included: age, gender, occupation, DM (including medication and duration), analgesics used, anthropometry, joints affected by pain and disease duration. Joint pain was scored by the patients using numerical rating scale. Pain severity score was calculated by adding the number of joints affected by pain and the maximum pain score. All analyses were adjusted and/or stratified by gender, age and body mass index. RESULTS In total, 489 patients with painful OA were included. From those, 139 patients had DM (30% males and 28% females, p=0.03). Pain severity, principally the number of joints affected by pain, and analgesic consumption, was higher in males with diabetes compared with males without diabetes (p=0.012 and OR=3.03; 95% CI 1.24 to 7.36, p=0.015, respectively). These associations were not significant in females (p=0.41 and p=0.66). Pain was more severe in males using insulin versus those who did not (p=0.025). Male subjects with diabetes had higher odds of hand pain or knee and hand pain compared with males without diabetes (OR=3.7, 95% CI 1.15 to 12; p=0.028 and OR=5.54; 95% CI 1.43 to 21.5, p=0.013, respectively). CONCLUSIONS Males with diabetes, especially those who require insulin, have more severe joint pain and consume more analgesics than males without diabetes or those who have DM and use other DM medication.
Collapse
Affiliation(s)
| | | | | | - Jordani Aragão
- Laboratory of Genetics Epidemiology, Faculdade de Medicina de Jundiai, Jundiai, Brazil
| | | | - Eduardo Gomes Machado
- Laboratory of Genetics Epidemiology, Faculdade de Medicina de Jundiai, Jundiai, Brazil
| | - Evaldo Marchi
- Laboratory of Genetics Epidemiology, Faculdade de Medicina de Jundiai, Jundiai, Brazil
| |
Collapse
|
|
28
|
Griffin TM, Huffman KM. Editorial: Insulin Resistance: Releasing the Brakes on Synovial Inflammation and Osteoarthritis? Arthritis Rheumatol 2018; 68:1330-3. [PMID: 26749517 DOI: 10.1002/art.39586] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2015] [Accepted: 01/05/2016] [Indexed: 12/15/2022]
Affiliation(s)
- Timothy M Griffin
- Oklahoma Medical Research Foundation and the University of Oklahoma Health Sciences Center, Oklahoma City
| | - Kim M Huffman
- Duke University Medical Center and Durham VA Medical Center, Durham, North Carolina
| |
Collapse
|
|
29
|
Eymard F, Parsons C, Edwards MH, Petit-Dop F, Reginster JY, Bruyère O, Chevalier X, Cooper C, Richette P. Statin use and knee osteoarthritis progression: Results from a post-hoc analysis of the SEKOIA trial. Joint Bone Spine 2017; 85:609-614. [PMID: 29037516 DOI: 10.1016/j.jbspin.2017.09.014] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2017] [Accepted: 09/27/2017] [Indexed: 02/06/2023]
Abstract
OBJECTIVE Epidemiological and experimental studies have suggested that lipid disorders might be involved in the pathophysiology of knee osteoarthritis (OA). Studies assessing the effect of statins on knee OA progression have shown conflicting results. We investigated the impact of statin use on radiological progression in patients with radiological and symptomatic knee OA. METHODS In total, 336 patients from the placebo arm of SEKOIA trial completed the 3-year follow-up and were included in this post-hoc analysis. Statin use was recorded at baseline interview. Minimal medial tibiofemoral joint space was measured on plain radiographs by an automated method at baseline and then annually. Radiologic progression was defined as joint space narrowing≥0.5mm over 3 years. RESULTS Overall, 71 patients were statin users (21.1%). They had a higher BMI (31.1±5.3 vs. 29.3±5.2kg/m2, P=0.008), a higher sum of metabolic factors (≥3 factors: 43.7% vs 7.2%; P for trend<0.001) and a higher rate of radiological progression (49.3% vs. 32.1%, P=0.007) as compared to statin non-users. The significant association between radiological progression and statin use was independent of age, gender, WOMAC global score, disease duration, baseline joint space width, hypertension, type 2 diabetes, obesity (BMI>30kg/m2) and cardiovascular diseases [relative risk 1.49 (95% CI: 1.10-2.02), P=0.010]. CONCLUSION Among patients with knee OA, statin use was associated with radiological worsening over 3 years, regardless of other potential confounding factors (obesity, type 2 diabetes, hypertension, disease duration, symptom intensity and radiological severity).
Collapse
Affiliation(s)
- Florent Eymard
- Department of rheumatology, Henri-Mondor hospital, AP-HP, 94010 Créteil cedex, France
| | - Camille Parsons
- MRC lifecourse epidemiology unit, Southampton general hospital, Southampton SO16 6YD, UK
| | - Mark H Edwards
- MRC lifecourse epidemiology unit, Southampton general hospital, Southampton SO16 6YD, UK
| | | | - Jean-Yves Reginster
- Department of public health and health economics, university of Liege, 4020 Liege, Belgium
| | - Olivier Bruyère
- Department of public health and health economics, university of Liege, 4020 Liege, Belgium
| | - Xavier Chevalier
- Department of rheumatology, Henri-Mondor hospital, AP-HP, 94010 Créteil cedex, France
| | - Cyrus Cooper
- MRC lifecourse epidemiology unit, Southampton general hospital, Southampton SO16 6YD, UK
| | - Pascal Richette
- Department of rheumatology, Lariboisière hospital, AP-HP, 75475 Paris cedex 10, France; Inserm U1132, university Paris 7, Lariboisière hospital, AP-HP, 75475 Paris cedex 10, France.
| |
Collapse
|
|
30
|
Bierma-Zeinstra S, Waarsing J. The role of atherosclerosis in osteoarthritis. Best Pract Res Clin Rheumatol 2017; 31:613-633. [DOI: 10.1016/j.berh.2018.08.006] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2018] [Revised: 05/16/2018] [Accepted: 07/06/2018] [Indexed: 01/06/2023]
|
|
31
|
Tootsi K, Märtson A, Kals J, Paapstel K, Zilmer M. Metabolic factors and oxidative stress in osteoarthritis: a case–control study. Scandinavian Journal of Clinical and Laboratory Investigation 2017; 77:520-526. [DOI: 10.1080/00365513.2017.1354255] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Affiliation(s)
- Kaspar Tootsi
- Department of Traumatology and Orthopaedics, University of Tartu, Tartu, Estonia
- Endothelial Centre, University of Tartu, Tartu, Estonia
- Department of Biochemistry, Institute of Biomedicine and Translational Medicine, Centre of Excellence for Genomics and Translational Medicine, University of Tartu, Tartu, Estonia
| | - Aare Märtson
- Department of Traumatology and Orthopaedics, University of Tartu, Tartu, Estonia
- Department of Biochemistry, Institute of Biomedicine and Translational Medicine, Centre of Excellence for Genomics and Translational Medicine, University of Tartu, Tartu, Estonia
- Clinic of Traumatology and Orthopaedics, Tartu University Hospital, Tartu, Estonia
| | - Jaak Kals
- Endothelial Centre, University of Tartu, Tartu, Estonia
- Department of Biochemistry, Institute of Biomedicine and Translational Medicine, Centre of Excellence for Genomics and Translational Medicine, University of Tartu, Tartu, Estonia
- Department of Surgery, University of Tartu, Tartu, Estonia
| | - Kaido Paapstel
- Endothelial Centre, University of Tartu, Tartu, Estonia
- Department of Biochemistry, Institute of Biomedicine and Translational Medicine, Centre of Excellence for Genomics and Translational Medicine, University of Tartu, Tartu, Estonia
| | - Mihkel Zilmer
- Department of Biochemistry, Institute of Biomedicine and Translational Medicine, Centre of Excellence for Genomics and Translational Medicine, University of Tartu, Tartu, Estonia
| |
Collapse
|
|
32
|
Hamada D, Maynard R, Schott E, Drinkwater CJ, Ketz JP, Kates SL, Jonason JH, Hilton MJ, Zuscik MJ, Mooney RA. Suppressive Effects of Insulin on Tumor Necrosis Factor-Dependent Early Osteoarthritic Changes Associated With Obesity and Type 2 Diabetes Mellitus. Arthritis Rheumatol 2017; 68:1392-402. [PMID: 26713606 PMCID: PMC4882234 DOI: 10.1002/art.39561] [Citation(s) in RCA: 79] [Impact Index Per Article: 9.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2015] [Accepted: 12/17/2015] [Indexed: 12/24/2022]
Abstract
Objective Obesity is a state of chronic inflammation that is associated with insulin resistance and type 2 diabetes mellitus (DM), as well as an increased risk of osteoarthritis (OA). This study was undertaken to define the links between obesity‐associated inflammation, insulin resistance, and OA, by testing the hypotheses that 1) tumor necrosis factor (TNF) is critical in mediating these pathologic changes in OA, and 2) insulin has direct effects on the synovial joint that are compromised by insulin resistance. Methods The effects of TNF and insulin on catabolic gene expression were determined in fibroblast‐like synoviocytes (FLS) isolated from human OA synovium. Synovial TNF expression and OA progression were examined in 2 mouse models, high‐fat (HF) diet–fed obese mice with type 2 DM and TNF‐knockout mice. Insulin resistance was investigated in synovium from patients with type 2 DM. Results Insulin receptors (IRs) were abundant in both mouse and human synovial membranes. Human OA FLS were insulin responsive, as indicated by the dose‐dependent phosphorylation of IRs and Akt. In cultures of human OA FLS with exogenous TNF, the expression and release of MMP1, MMP13, and ADAMTS4 by FLS were markedly increased, whereas after treatment with insulin, these effects were selectively inhibited by >50%. The expression of TNF and its abundance in the synovium were elevated in samples from obese mice with type 2 DM. In TNF‐knockout mice, increases in osteophyte formation and synovial hyperplasia associated with the HF diet were blunted. The synovium from OA patients with type 2 DM contained markedly more macrophages and showed elevated TNF levels as compared to the synovium from OA patients without diabetes. Moreover, insulin‐dependent phosphorylation of IRs and Akt was blunted in cultures of OA FLS from patients with type 2 DM. Conclusion TNF appears to be involved in mediating the advanced progression of OA seen in type 2 DM. While insulin plays a protective, antiinflammatory role in the synovium, insulin resistance in patients with type 2 DM may impair this protective effect and promote the progression of OA.
Collapse
Affiliation(s)
- Daisuke Hamada
- University of Rochester Medical Center, Rochester, New York
| | - Robert Maynard
- University of Rochester Medical Center, Rochester, New York
| | - Eric Schott
- University of Rochester Medical Center, Rochester, New York
| | | | - John P Ketz
- University of Rochester Medical Center, Rochester, New York
| | | | | | | | | | | |
Collapse
|
|
33
|
Eaton CB, Sayeed M, Ameernaz S, Roberts MB, Maynard JD, Driban JB, McAlindon TE. Sex differences in the association of skin advanced glycation endproducts with knee osteoarthritis progression. Arthritis Res Ther 2017; 19:36. [PMID: 28212675 PMCID: PMC5316210 DOI: 10.1186/s13075-017-1226-z] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2016] [Accepted: 01/09/2017] [Indexed: 12/16/2022] Open
Abstract
Background The accumulation of advanced glycation endproducts in articular cartilage has been suggested as an etiologic factor in the development and progression of knee osteoarthritis (KOA). Methods We conducted a prospective cohort study of skin advanced glycation endproducts (sAGEs) measured non-invasively by skin intrinsic fluorescence and the relationship between sAGE KOA progression in 160 men and 287 women in a sub-cohort of the Osteoarthritis Initiative at a single site. KOA progression was measured by yearly changes in Osteoarthritis Research Society International (OARSI)-defined joint space narrowing (JSN) and by yearly changes in joint space width (JSW) from baseline to 48 months. Sex-stratified repeated measures, mixed models to account for correlation between the knees within persons and adjusted for age, body mass index (BMI), Kellgren-Lawrence (KL) grade, beam angle and rim-to-rim distance were utilized. Results Increasing tertiles of sAGE measured at 36 months were associated with greater JSN over 4 years in men but not in women. The percentage of knees with JSN at 48 months, by tertiles of sAGE, were 7.0%, 16.0% and 17.7% in men (p for linear trend = 0.03) and 11.4%, 14.4% and 8.4% in women (p for linear trend = 0.33). Using change in JSW as the outcome, a similar trend was found in men but it was not statistically significant in fully adjusted models and no association was found in women. Conclusion This study provides preliminary evidence that sAGEs independent of age and BMI, are associated with knee JSN in men but not in women. Electronic supplementary material The online version of this article (doi:10.1186/s13075-017-1226-z) contains supplementary material, which is available to authorized users.
Collapse
Affiliation(s)
- Charles B Eaton
- Alpert Medical School of Brown University, Providence, USA. .,School of Public Health of Brown University, Providence, USA. .,Center of Primary Care and Prevention, Memorial Hospital of Rhode Island, 111 Brewster Street, Pawtucket, RI, 02860, USA.
| | - Maria Sayeed
- Department of Medicine, Memorial Hospital of Rhode Island, 111 Brewster Street, Pawtucket, RI, USA
| | - Syeda Ameernaz
- Center of Primary Care and Prevention, Memorial Hospital of Rhode Island, 111 Brewster Street, Pawtucket, RI, 02860, USA
| | - Mary B Roberts
- Center of Primary Care and Prevention, Memorial Hospital of Rhode Island, 111 Brewster Street, Pawtucket, RI, 02860, USA
| | - John D Maynard
- Vera Light Inc., 800 Bradbury Dr SE # 217, Albuquerque, NM, USA
| | - Jeffrey B Driban
- Division of Rheumatology, Tufts Medical Center, 800 Washington Street, Box 406, Boston, MA, USA
| | - Timothy E McAlindon
- Division of Rheumatology, Tufts Medical Center, 800 Washington Street, Box 406, Boston, MA, USA
| |
Collapse
|
|
34
|
Oral Administration of Resveratrol Alleviates Osteoarthritis Pathology in C57BL/6J Mice Model Induced by a High-Fat Diet. Mediators Inflamm 2017; 2017:7659023. [PMID: 28250578 PMCID: PMC5303602 DOI: 10.1155/2017/7659023] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2016] [Accepted: 01/10/2017] [Indexed: 01/22/2023] Open
Abstract
Obesity has been associated with osteoarthritis (OA) due to increased mass and metabolic factors which are independent of the biomechanical contribution to joint load. Resveratrol, a natural polyphenolic compound, exerts protective effects on OA through its anti-inflammatory property. However, the mechanism of resveratrol on obesity-related OA is unclear. To investigate the effect and possible mechanism of oral resveratrol on obesity-related OA, we fed C57BL/6J mice with a high-fat diet (HFD) for 16 weeks to establish obesity-related OA model; then two doses (22.5 mg/kg and 45 mg/kg) of resveratrol were given by gavage for additional 12 weeks. Mice with HFD significantly increased body weights compared to the control mice, while resveratrol treatment did not cause obvious weight loss. Histological assessments showed that resveratrol at 45 mg/kg significantly improved OA symptoms. Levels of serum IL-1β and leptin were decreased by resveratrol treatment and positively correlated with Mankin scores. Moreover, resveratrol significantly inhibited the expression of TLR4 and TRAF6 in cartilage. These results suggest that HFD induced obesity can lead to the occurrence of OA, and resveratrol may alleviate OA pathology by decreasing the levels of systematic inflammation and/or inhibiting TLR4 signaling pathway in cartilage. Thus, resveratrol might be a promising therapeutic treatment for obesity-related OA.
Collapse
|
|
35
|
Leung YY, Allen JC, Ang LW, Yuan JM, Koh WP. Diabetes mellitus and the risk of total knee replacement among Chinese in Singapore, the Singapore Chinese Health Study. Sci Rep 2017; 7:40671. [PMID: 28084472 PMCID: PMC5233971 DOI: 10.1038/srep40671] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2016] [Accepted: 12/09/2016] [Indexed: 01/15/2023] Open
Abstract
Association between diabetes mellitus (diabetes) and risk of knee osteoarthritis (KOA) is confounded by high body mass index (BMI), a strong risk factor for both conditions. We evaluated the association between diabetes and incidence of total knee replacement (TKR) due to severe KOA in the Singapore Chinese Health Study, a prospective cohort of 63,257 Chinese men and women, aged 45-74 years at recruitment in 1993-1998, and re-interviewed in 1999-2004. Height, weight, lifestyle factors and history of diabetes were obtained through in-person interviews at recruitment and re-interview. Incident cases of TKR were identified via record linkage with nationwide hospital discharge database. Subjects with/without prevalent diabetes had comparable BMI (24.0 kg/m2 versus 23.0 kg/m2). After an average of 14-years, 1,973 subjects had TKR attributable to KOA. Compared to subjects without diabetes, hazard ratio (HR) of TKR for subjects with diabetes was 0.63 [95% confidence interval (CI), 0.52-0.75] after controlling for BMI and other risk factors. An inverse association was also observed between incident diabetes at re-interview and subsequent risk of TKR (HR = 0.74; 95% CI = 0.58-0.94). The inverse diabetes-TKR risk association was similar by gender and across three categories of BMI. Our study does not support diabetes as a risk factor of KOA.
Collapse
Affiliation(s)
- Ying-Ying Leung
- Duke-NUS Medical School, Singapore.,Department of Rheumatology and Immunology, Singapore General Hospital, Singapore
| | | | - Li-Wei Ang
- Epidemiology &Disease Control Division, Ministry of Health, Singapore
| | - Jian-Min Yuan
- Division of Cancer Control and Population Sciences, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania, USA.,Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Woon-Puay Koh
- Duke-NUS Medical School, Singapore.,Saw Swee Hock School of Public Health, National University of Singapore, Singapore
| |
Collapse
|
|
36
|
June RK, Liu-Bryan R, Long F, Griffin TM. Emerging role of metabolic signaling in synovial joint remodeling and osteoarthritis. J Orthop Res 2016; 34:2048-2058. [PMID: 27605370 PMCID: PMC5365077 DOI: 10.1002/jor.23420] [Citation(s) in RCA: 61] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2016] [Accepted: 08/31/2016] [Indexed: 02/04/2023]
Abstract
Obesity and associated metabolic diseases collectively referred to as the metabolic syndrome increase the risk of skeletal and synovial joint diseases, including osteoarthritis (OA). The relationship between obesity and musculoskeletal diseases is complex, involving biomechanical, dietary, genetic, inflammatory, and metabolic factors. Recent findings illustrate how changes in cellular metabolism and metabolic signaling pathways alter skeletal development, remodeling, and homeostasis, especially in response to biomechanical and inflammatory stressors. Consequently, a better understanding of the energy metabolism of diarthrodial joint cells and tissues, including bone, cartilage, and synovium, may lead to new strategies to treat or prevent synovial joint diseases such as OA. This rationale was the basis of a workshop presented at the 2016 Annual ORS Meeting in Orlando, FL on the emerging role of metabolic signaling in synovial joint remodeling and OA. The topics we covered included (i) the relationship between metabolic syndrome and OA in clinical and pre-clinical studies; (ii) the effect of biomechanical loading on chondrocyte metabolism; (iii) the effect of Wnt signaling on osteoblast carbohydrate and amino acid metabolism with respect to bone anabolism; and (iv) the role of AMP-activated protein kinase in chondrocyte energetic and biomechanical stress responses in the context of cartilage injury, aging, and OA. Although challenges exist for measuring in vivo changes in synovial joint tissue metabolism, the findings presented herein provide multiple lines of evidence to support a central role for disrupted cellular energy metabolism in the pathogenesis of OA. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:2048-2058, 2016.
Collapse
Affiliation(s)
- Ronald K. June
- Depts. of Mechanical & Industrial Engineering and Cell Biology & Neuroscience, Montana State University, Bozeman, MT, USA
| | - Ru Liu-Bryan
- VA San Diego Healthcare System, Dept. of Medicine, University of California San Diego, San Diego, California, USA
| | - Fanxing Long
- Dept. of Orthopaedic Surgery, Dept. of Developmental Biology, Washington University School of Medicine, St. Louis, MO, USA
| | - Timothy M. Griffin
- Aging and Metabolism Research Program, Oklahoma Medical Research Foundation, Depts. of Biochemistry and Molecular Biology, Physiology, and Geriatric Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
| |
Collapse
|
|
37
|
Paxton RJ, Murray AM, Stevens-Lapsley JE, Sherk KA, Christiansen CL. Physical activity, ambulation, and comorbidities in people with diabetes and lower-limb amputation. JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT 2016; 53:1069-1078. [PMID: 28355032 PMCID: PMC5474964 DOI: 10.1682/jrrd.2015.08.0161] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/25/2015] [Revised: 12/01/2015] [Indexed: 11/05/2022]
Abstract
We characterized physical activity (PA) and its relation to physical function and number of comorbidities in people with diabetes and transtibial amputation (AMP), people with diabetes without AMP, and nondisabled adults without diabetes or AMP. Twenty-two individuals with type 2 diabetes mellitus (DM) and transtibial amputation (DM+AMP), 11 people with DM, and 13 nondisabled participants were recruited for this cross-sectional cohort study. Measures included PA volume and intensity, a Timed Up and Go test, a 2-min walk test, and number of comorbidities. The nondisabled group performed greater amounts of PA than the DM group, who performed greater amounts of PA than the DM+AMP group. PA was related to physical function in the DM group and in the DM+AMP group, whereas no such relationship existed in the nondisabled group. PA was not related to number of comorbidities in any group. These findings suggest the ability to walk may affect overall performance of PA. Alternately, PA may alleviate walking problems. This possibility is of interest because issues with walking may be modifiable by improved levels and intensity of PA. PA's lack of relation to number of comorbidities suggests that factors beyond multiple morbidities account for group differences in PA.
Collapse
Affiliation(s)
- Roger J. Paxton
- Physical Therapy Program, Department of Physical Medicine and Rehabilitation, University of Colorado, Aurora, CO
| | - Amanda M. Murray
- Physical Therapy Program, Department of Physical Medicine and Rehabilitation, University of Colorado, Aurora, CO
- Geriatric Research Education and Clinical Center, Department of Veterans Affairs Eastern Colorado Healthcare System, Denver, CO
| | - Jennifer E. Stevens-Lapsley
- Physical Therapy Program, Department of Physical Medicine and Rehabilitation, University of Colorado, Aurora, CO
- Geriatric Research Education and Clinical Center, Department of Veterans Affairs Eastern Colorado Healthcare System, Denver, CO
| | | | - Cory L. Christiansen
- Physical Therapy Program, Department of Physical Medicine and Rehabilitation, University of Colorado, Aurora, CO
- Geriatric Research Education and Clinical Center, Department of Veterans Affairs Eastern Colorado Healthcare System, Denver, CO
| |
Collapse
|
|
38
|
Santangelo KS, Radakovich LB, Fouts J, Foster MT. Pathophysiology of obesity on knee joint homeostasis: contributions of the infrapatellar fat pad. Horm Mol Biol Clin Investig 2016; 26:97-108. [DOI: 10.1515/hmbci-2015-0067] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2015] [Accepted: 12/15/2015] [Indexed: 12/29/2022]
Abstract
AbstractOsteoarthritis (OA) is a debilitating condition characterized by inflammation, breakdown, and consequent loss of cartilage of the joints. Epidemiological studies indicate obesity is an important risk factor involved in OA initiation and progression. Traditional views propose OA to be a biomechanical consequence of excess weight on weight-bearing joints; however, emerging data demonstrates that systemic and local factors released from white adipose depots play a role. Hence, current views characterize OA as a condition exacerbated by a metabolic link related to adipose tissue, and not solely related to redistributed/altered weight load. Factors demonstrated to influence cartilage and bone homeostasis include adipocyte-derived hormones (“adipokines”) and adipose depot released cytokines. Epidemiological studies demonstrate a positive relation between systemic circulating cytokines, leptin, and resistin with OA types, while the association with adiponectin is controversial. Local factors in joints have also been shown to play a role in OA. In particular, this includes the knee, a weight-bearing joint that encloses a relatively large adipose depot, the infrapatellar fat pad (IFP), which serves as a source of local inflammatory factors. This review summarizes the relation of obesity and OA as it specifically relates to the IFP and other integral supporting structures. Overall, studies support the concept that metabolic effects associated with systemic obesity also extend to the IFP, which promotes inflammation, pain, and cartilage destruction within the local knee joint environment, thus contributing to development and progression of OA.
Collapse
|
|
39
|
Zheng S, Xu J, Xu S, Zhang M, Huang S, He F, Yang X, Xiao H, Zhang H, Ding C. Association between circulating adipokines, radiographic changes, and knee cartilage volume in patients with knee osteoarthritis. Scand J Rheumatol 2015; 45:224-229. [PMID: 26505548 DOI: 10.3109/03009742.2015.1083053] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/11/2015] [Indexed: 11/13/2022]
Abstract
OBJECTIVES To explore the associations between serum adipokine levels, radiographic osteoarthritis (ROA) severity, and articular cartilage volume in patients with knee OA. METHOD A cross-sectional sample of 205 patients (aged 45-74 years) with knee OA were consecutively recruited to the Anhui Osteoarthritis (AHOA) study. ROA was assessed using the Kellgren-Lawrence (KL) grading system (grades 0-4). Knee cartilage volume was determined using fat-saturated T1-weighted magnetic resonance imaging (MRI). Serum levels of the adipokines leptin, adiponectin, and resistin were measured by using an enzyme-linked immunosorbent assay (ELISA). RESULTS Serum adiponectin, but not serum leptin or resitin, was significantly associated with reduced ROA severity in univariable analyses and this association remained significant after adjustment for age, sex, body mass index (BMI), and disease duration [β = -0.012, 95% confidence interval (CI) -0.021 to -0.002]. In ROA patients, leptin was significantly and positively associated with knee cartilage volume at patellar and medial tibial sites in both unadjusted and adjusted analyses (β = 0.006, 95% CI 0.02-0.010 for medial tibia and β = 0.009, 95% CI 0.001-0.018 for patella sites) but adiponectin and resistin had no significant associations with cartilage volume. In non-ROA patients, leptin, adiponectin, and resistin were not significantly associated with cartilage volume at any site. CONCLUSIONS Serum levels of leptin are independently associated with increased knee cartilage volume. In addition, serum adiponectin is significantly and negatively associated with ROA severity, suggesting a potentially protective effect.
Collapse
Affiliation(s)
- S Zheng
- a Department of Rheumatology and Immunology , First Affiliated Hospital of Anhui Medical University , Hefei , PR China
| | - J Xu
- a Department of Rheumatology and Immunology , First Affiliated Hospital of Anhui Medical University , Hefei , PR China
| | - S Xu
- a Department of Rheumatology and Immunology , First Affiliated Hospital of Anhui Medical University , Hefei , PR China
| | - M Zhang
- a Department of Rheumatology and Immunology , First Affiliated Hospital of Anhui Medical University , Hefei , PR China
| | - S Huang
- a Department of Rheumatology and Immunology , First Affiliated Hospital of Anhui Medical University , Hefei , PR China
| | - F He
- a Department of Rheumatology and Immunology , First Affiliated Hospital of Anhui Medical University , Hefei , PR China
| | - X Yang
- a Department of Rheumatology and Immunology , First Affiliated Hospital of Anhui Medical University , Hefei , PR China
| | - H Xiao
- a Department of Rheumatology and Immunology , First Affiliated Hospital of Anhui Medical University , Hefei , PR China
| | - H Zhang
- b Department of Radiology , First Affiliated Hospital of Anhui Medical University , Hefei , PR China
| | - C Ding
- c Menzies Institute of Medical Research , University of Tasmania , Australia
- d Department of Epidemiology and Preventive Medicine , Monash University Medical School , Tasmania , Australia
| |
Collapse
|
|
40
|
Paxton RJ, Melanson EL, Stevens-Lapsley JE, Christiansen CL. Physical activity after total knee arthroplasty: A critical review. World J Orthop 2015; 6:614-622. [PMID: 26396937 PMCID: PMC4573505 DOI: 10.5312/wjo.v6.i8.614] [Citation(s) in RCA: 51] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2015] [Revised: 05/07/2015] [Accepted: 07/02/2015] [Indexed: 02/06/2023] Open
Abstract
Total knee arthroplasty (TKA) is the most commonly performed elective surgery in the United States. TKA typically improves functional performance and reduces pain associated with knee osteoarthritis. Little is known about the influence of TKA on overall physical activity levels. Physical activity, defined as “any bodily movement produced by skeletal muscles that results in energy expenditure”, confers many health benefits but typically decreases with endstage osteoarthritis. The purpose of this review is to describe the potential benefits (metabolic, functional, and orthopedic) of physical activity to patients undergoing TKA, present results from recent studies aimed to determine the effect of TKA on physical activity, and discuss potential sources of variability and conflicting results for physical activity outcomes. Several studies utilizing self-reported outcomes indicate that patients perceive themselves to be more physically active after TKA than they were before surgery. Accelerometry-based outcomes indicate that physical activity for patients after TKA remains at or below pre-surgical levels. Several different factors likely contributed to these variable results, including the use of different instruments, duration of follow-up, and characteristics of the subjects studied. Comparison to norms, however, suggests that daily physical activity for patients following TKA may fall short of healthy age-matched controls. We propose that further study of the relationship between TKA and physical activity needs to be performed using accelerometry-based outcome measures at multiple post-surgical time points.
Collapse
|
|
41
|
Differences in the prevalence and characteristics of metabolic syndrome in rheumatoid arthritis and osteoarthritis: a multicentric study. Rheumatol Int 2015; 35:2047-57. [DOI: 10.1007/s00296-015-3307-0] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2015] [Accepted: 06/02/2015] [Indexed: 01/16/2023]
|
|
42
|
Louati K, Vidal C, Berenbaum F, Sellam J. Association between diabetes mellitus and osteoarthritis: systematic literature review and meta-analysis. RMD Open 2015; 1:e000077. [PMID: 26535137 PMCID: PMC4613158 DOI: 10.1136/rmdopen-2015-000077] [Citation(s) in RCA: 227] [Impact Index Per Article: 22.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2015] [Revised: 03/16/2015] [Accepted: 03/17/2015] [Indexed: 01/02/2023] Open
Abstract
Objectives To investigate the prevalence of osteoarthritis (OA) in patients with diabetes mellitus (DM) and prevalence of DM in patients with OA and whether OA and DM are associated. Design A systematic literature review and meta-analysis. We included cohort, case–control and cross-sectional studies assessing the number of patients with DM and/or OA. The mean prevalence of OA among patients with DM and DM among patients with OA was calculated. Data from trials assessing an association of diabetes and OA were pooled and results are presented as unadjusted OR and 95% CI. Results From the 299 publications, we included 49 studies in the analysis, including 28 cross-sectional studies, 11 cohort studies and 10 case–control studies. In all, 21, 5 and 23 articles involved patients with OA exclusively, patients with DM and the general population, respectively. For 5788 patients with DM, the mean OA prevalence was 29.5±1.2%. For 645 089 patients with OA, the prevalence of DM was 14.4±0.1%. The risk of OA was greater in the DM than non-DM population (OR=1.46 (1.08 to 1.96), p=0.01), as was DM in the OA than non-OA population (OR=1.41 (1.21 to 1.65), p<0.00 001). Among the 12 studies reporting an OR adjusted on at least the body mass index, 5 showed no association of DM and OA and 7 identified DM as an independent risk factor. Conclusions This meta-analysis highlights a high frequency of OA in patients with DM and an association between both diseases, representing a further step towards the individualisation of DM-related OA within a metabolic OA phenotype.
Collapse
Affiliation(s)
- Karine Louati
- Department of Rheumatology , Assistance Publique-Hôpitaux de Paris (AP-HP), Saint-Antoine Hospital , Paris , France ; Inflammation-Immunopathology-Biotherapy Department (DHU i2B), Paris , France ; Sorbonne Universités, UPMC Univ Paris 06 , Paris , France
| | - Céline Vidal
- Department of Rheumatology , Assistance Publique-Hôpitaux de Paris (AP-HP), Saint-Antoine Hospital , Paris , France ; Inflammation-Immunopathology-Biotherapy Department (DHU i2B), Paris , France
| | - Francis Berenbaum
- Department of Rheumatology , Assistance Publique-Hôpitaux de Paris (AP-HP), Saint-Antoine Hospital , Paris , France ; Inflammation-Immunopathology-Biotherapy Department (DHU i2B), Paris , France ; Sorbonne Universités, UPMC Univ Paris 06 , Paris , France ; Faculté de Médecine Saint Antoine , INSERM UMR_S 938 , Paris , France
| | - Jérémie Sellam
- Department of Rheumatology , Assistance Publique-Hôpitaux de Paris (AP-HP), Saint-Antoine Hospital , Paris , France ; Inflammation-Immunopathology-Biotherapy Department (DHU i2B), Paris , France ; Sorbonne Universités, UPMC Univ Paris 06 , Paris , France ; Faculté de Médecine Saint Antoine , INSERM UMR_S 938 , Paris , France
| |
Collapse
|
|
43
|
Eymard F, Parsons C, Edwards MH, Petit-Dop F, Reginster JY, Bruyère O, Richette P, Cooper C, Chevalier X. Diabetes is a risk factor for knee osteoarthritis progression. Osteoarthritis Cartilage 2015; 23:851-9. [PMID: 25655678 DOI: 10.1016/j.joca.2015.01.013] [Citation(s) in RCA: 129] [Impact Index Per Article: 12.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/13/2014] [Revised: 01/19/2015] [Accepted: 01/23/2015] [Indexed: 02/02/2023]
Abstract
PURPOSE Recent studies have suggested that metabolic factors (obesity, diabetes, hypertension and dyslipidemia) and their clustering in metabolic syndrome (MetS) might be involved in the pathophysiology of knee osteoarthritis (OA). We investigated their impact on radiographic progression by an annualised measure of the joint space narrowing (JSN) of the medial tibiofemoral compartment. METHODS 559 patients older than 50 years with symptomatic knee OA were recruited for the placebo arm of the SEKOIA trial. The presence of diabetes, hypertension and dyslipidemia was determined at baseline interview. Body mass index (BMI) was calculated, obesity was considered >30 kg/m(2). MetS was defined by the sum of metabolic factors ≥ 3. Minimal medial tibiofemoral joint space on plain radiographs was measured by an automated method at baseline and then annually for up to 3 years. RESULTS The mean age of patients was 62.8 [62.2-63.4] years; 392 were women. A total of 43.8% was obese, 6.6% had type 2 diabetes, 45.1% hypertension, 27.6% dyslipidemia and 13.6% MetS. Mean annualised JSN was greater for patients with type 2 diabetes than without diabetes (0.26 [-0.35 to -0.17] vs 0.14 [-0.16 to -0.12] mm; P = 0.001). This association remained significant after adjustment for sex, age, BMI, hypertension and dyslipidemia (P = 0.018). In subgroup analysis, type 2 diabetes was a significant predictor of JSN in males but not females. The other metabolic factors and MetS were not associated with annualised JSN. CONCLUSION Type 2 diabetes was a predictor of joint space reduction in men with established knee OA. No relationships were found between MetS or other metabolic factors and radiographic progression.
Collapse
Affiliation(s)
- F Eymard
- Department of Rheumatology, AP-HP Henri Mondor Hospital, F-94010 Créteil Cedex, France
| | - C Parsons
- MRC Lifecourse Epidemiology Unit, Southampton General Hospital, SO16 6YD Southampton, UK
| | - M H Edwards
- MRC Lifecourse Epidemiology Unit, Southampton General Hospital, SO16 6YD Southampton, UK
| | - F Petit-Dop
- Clinical Department, Servier Laboratory, 92150 Suresnes, France
| | - J-Y Reginster
- Department of Public Health and Health Economics, University of Liege, 4020 Liege, Belgium
| | - O Bruyère
- Department of Public Health and Health Economics, University of Liege, 4020 Liege, Belgium
| | - P Richette
- Department of Rheumatology, AP-HP Lariboisière Hospital, F-75475 Paris Cedex 10, France
| | - C Cooper
- MRC Lifecourse Epidemiology Unit, Southampton General Hospital, SO16 6YD Southampton, UK
| | - X Chevalier
- Department of Rheumatology, AP-HP Henri Mondor Hospital, F-94010 Créteil Cedex, France.
| |
Collapse
|
|
44
|
Kluzek S, Arden NK, Newton J. Adipokines as potential prognostic biomarkers in patients with acute knee injury. Biomarkers 2015; 20:519-25. [PMID: 26006054 PMCID: PMC4819580 DOI: 10.3109/1354750x.2014.948914] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
This review considers adipokines as predictive biomarkers for early onset post-traumatic knee osteoarthritis (KOA). Serum concentrations of leptin and resistin can predict radiographic changes and are elevated in early KOA, with higher leptin concentrations independently associated with more severe knee changes. Plasma concentrations of resistin are chronically elevated after injury. Leptin, resistin, chemerin and vistfatin induce catabolic enzymes associated with cartilage degeneration. Available literature on adipokines in post-traumatic KOA pathogenesis suggests that they could contribute to risk prediction of early onset post-traumatic KOA. Further research is needed to further understand the association between adipokines, synovitis and long-term outcomes in this population.
Collapse
Affiliation(s)
- Stefan Kluzek
- a Nuffield Department of Orthopaedics , Rheumatology and Musculoskeletal Sciences, University of Oxford , Oxford , UK
| | - Nigel K Arden
- b Oxford NIHR Musculoskeletal Biomedical Research Unit, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences , University of Oxford , Oxford , UK , and.,c MRC Lifecourse Epidemiology Unit , University of Southampton, Southampton General Hospital , Southampton , UK
| | - Julia Newton
- a Nuffield Department of Orthopaedics , Rheumatology and Musculoskeletal Sciences, University of Oxford , Oxford , UK
| |
Collapse
|
|
45
|
Significance of increased leptin expression in osteoarthritis patients. PLoS One 2015; 10:e0123224. [PMID: 25893833 PMCID: PMC4403877 DOI: 10.1371/journal.pone.0123224] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2014] [Accepted: 03/01/2015] [Indexed: 01/08/2023] Open
Abstract
OBJECTIVE Alterations in leptin expression contributes to the progression of various diseases, including cancers. This meta-analysis investigated the clinical significance of leptin levels in osteoarthritis (OA) patients, with the goal of building a leptin-based diagnostic criterion for OA. METHOD Multiple scientific databases in English and Chinese languages, such as the Cochrane Library Database, CINAHL, Chinese Biomedical (CBM), EMBASE, PubMed, and Web of Science, were exhaustively searched, without any language restrictions, to identify high-quality studies relevant to leptin and OA. Version 12.0 STATA software was used for data analysis. We used odds ratios (OR) and 95% confidence intervals (CI) to test the correlation between serum leptin levels and OA progression. RESULTS A total of 11 clinical studies were finally selected for their high quality and relevance to the topic in this meta-analysis. The 11 case-control studies contained a combined total of 3,625 subjects. The meta-analysis results showed that leptin expression was significantly increased in OA patients, compared with the controls (SMD = 0.87, 95%CI: 0.72-1.02, P < 0.001), and there was also a strong association between leptin expression levels and gender (SMD = 8.55, 95%CI: 4.74-12.35, P < 0.001). In ethnicity-stratified subgroup analysis, all the study populations, irrespective of ethnicity, showed remarkably high leptin expression levels in females and in OA patients (all P < 0.05), compared to their respective counterparts. CONCLUSION The present study revealed that increased leptin expression levels are associated with disease severity in OA patients, especially among the female OA patients. Based on our results, we propose that leptin level may be a useful biomarker for the assessment of the clinical status in OA patients.
Collapse
|
|
46
|
Wang X, Hunter D, Xu J, Ding C. Metabolic triggered inflammation in osteoarthritis. Osteoarthritis Cartilage 2015; 23:22-30. [PMID: 25452156 DOI: 10.1016/j.joca.2014.10.002] [Citation(s) in RCA: 184] [Impact Index Per Article: 18.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2014] [Revised: 09/23/2014] [Accepted: 10/06/2014] [Indexed: 02/02/2023]
Abstract
Osteoarthritis (OA) is a common chronic joint disorder with a multifactorial etiology including genetic and environmental factors. Metabolic triggered inflammation, induced by nutrient overload and metabolic surplus, consists of components such as obesity, pro-inflammatory cytokines and adipokines, abnormal metabolites, acute phase proteins, vitamin D deficiency, and deregulated microRNAs that may play a role in OA pathophysiology. Obesity-related metabolic factors, especially adipokines, contribute to OA development by inducing pro-inflammatory cytokines and degradative enzymes, leading to cartilage matrix impairment and subchondral bone remodeling. Ectopic metabolite deposition and low-grade systemic inflammation can contribute to a toxic internal environment that exacerbates OA. Complement components highly expressed in osteoarthritic joints have also been proposed as causative factors. Vitamin D deficiency has been associated with obesity and is implicated to be associated with cartilage loss in OA. Metabolic microRNAs may explain the inflammatory link between obesity and OA. Therapies targeting metabolic-triggered inflammation and its components are anticipated to have potential for the treatment of OA.
Collapse
Affiliation(s)
- X Wang
- Menzies Research Institute Tasmania, University of Tasmania, Hobart, Tasmania, Australia
| | - D Hunter
- Institute of Bone and Joint Research, Kolling Institute and Royal North Shore Hospital, University of Sydney, Sydney, NSW, Australia
| | - J Xu
- Department of Rheumatology and Arthritis Research Institute, 1st Affiliated Hospital, Anhui Medical University, Hefei, China
| | - C Ding
- Menzies Research Institute Tasmania, University of Tasmania, Hobart, Tasmania, Australia; Institute of Bone and Joint Research, Kolling Institute and Royal North Shore Hospital, University of Sydney, Sydney, NSW, Australia; Department of Rheumatology and Arthritis Research Institute, 1st Affiliated Hospital, Anhui Medical University, Hefei, China.
| |
Collapse
|
|
47
|
Karvonen-Gutierrez CA, Harlow SD, Jacobson J, Mancuso P, Jiang Y. The relationship between longitudinal serum leptin measures and measures of magnetic resonance imaging-assessed knee joint damage in a population of mid-life women. Ann Rheum Dis 2014; 73:883-9. [PMID: 23576710 PMCID: PMC3884071 DOI: 10.1136/annrheumdis-2012-202685] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
BACKGROUND AND OBJECTIVE Serum leptin measures are associated with radiographic knee osteoarthritis, but no studies have examined leptin levels with respect to different measures of knee joint damage from MRI. METHODS Participants in the Michigan Study of Women's Health Across the Nation underwent bilateral knee MRIs at follow-up visit 11 for assessment of cartilage defects, bone marrow lesions, osteophytes, meniscal tears, synovitis and joint effusion. Serum leptin measures were available from baseline, follow-up visits 1 and 3-7. RESULTS Baseline serum leptin levels were associated with greater odds of having more severe knee joint damage at follow-up visit 11 after adjustment for age, smoking status, menopause status and body mass index residuals. The greatest effect was observed for osteophytes; a 5 ng/ml increase in baseline leptin was associated with 24% higher odds of having larger osteophytes (95% CI 1.17 to 1.32). Correlations with baseline serum leptin were greatest for MRI-assessed osteophytes (r=0.41), followed by effusion (r=0.32), synovitis (r=0.30), cartilage defects (r=0.28), bone marrow lesions (r=0.24) and meniscal abnormalities (r=0.21). CONCLUSIONS Leptin levels 10 years prior to MRI assessment were associated with the presence of cartilage defects, bone marrow lesions, osteophytes, meniscal tears, synovitis and effusion among a population of middle-aged women. Understanding the role that leptin plays in the joint degradation process is critical for development of more targeted interventions for osteoarthritis.
Collapse
|
|
48
|
Abella V, Scotece M, Conde J, López V, Lazzaro V, Pino J, Gómez-Reino JJ, Gualillo O. Adipokines, metabolic syndrome and rheumatic diseases. J Immunol Res 2014; 2014:343746. [PMID: 24741591 PMCID: PMC3987880 DOI: 10.1155/2014/343746] [Citation(s) in RCA: 102] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2013] [Revised: 01/10/2014] [Accepted: 01/10/2014] [Indexed: 02/06/2023] Open
Abstract
The metabolic syndrome (MetS) is a cluster of cardiometabolic disorders that result from the increasing prevalence of obesity. The major components of MetS include insulin resistance, central obesity, dyslipidemia, and hypertension. MetS identifies the central obesity with increased risk for cardiovascular diseases (CVDs) and type-2 diabetes mellitus (T2DM). Patients with rheumatic diseases, such as rheumatoid arthritis, osteoarthritis, systemic lupus erythematosus, and ankylosing spondylitis, have increased prevalence of CVDs. Moreover, CVD risk is increased when obesity is present in these patients. However, traditional cardiovascular risk factors do not completely explain the enhanced cardiovascular risk in this population. Thus, MetS and the altered secretion patterns of proinflammatory adipokines present in obesity could be the link between CVDs and rheumatic diseases. Furthermore, adipokines have been linked to the pathogenesis of MetS and its comorbidities through their effects on vascular function and inflammation. In the present paper, we review recent evidence of the role played by adipokines in the modulation of MetS in the general population, and in patients with rheumatic diseases.
Collapse
Affiliation(s)
- Vanessa Abella
- SERGAS, Research Laboratory 9, NEIRID Lab (Neuroendocrine Interactions in Rheumatology and Inflammatory Diseases), Institute of Medical Research (IDIS), Santiago University Clinical Hospital, 15706 Santiago de Compostela, Spain ; Department of Molecular and Cellular Biology, University of Coruña (UDC), 15071 A Coruña, Spain
| | - Morena Scotece
- SERGAS, Research Laboratory 9, NEIRID Lab (Neuroendocrine Interactions in Rheumatology and Inflammatory Diseases), Institute of Medical Research (IDIS), Santiago University Clinical Hospital, 15706 Santiago de Compostela, Spain
| | - Javier Conde
- SERGAS, Research Laboratory 9, NEIRID Lab (Neuroendocrine Interactions in Rheumatology and Inflammatory Diseases), Institute of Medical Research (IDIS), Santiago University Clinical Hospital, 15706 Santiago de Compostela, Spain
| | - Verónica López
- SERGAS, Research Laboratory 9, NEIRID Lab (Neuroendocrine Interactions in Rheumatology and Inflammatory Diseases), Institute of Medical Research (IDIS), Santiago University Clinical Hospital, 15706 Santiago de Compostela, Spain
| | - Verónica Lazzaro
- SERGAS, Research Laboratory 9, NEIRID Lab (Neuroendocrine Interactions in Rheumatology and Inflammatory Diseases), Institute of Medical Research (IDIS), Santiago University Clinical Hospital, 15706 Santiago de Compostela, Spain ; University Magna Graecia of Catanzaro, 88100 Catanzaro, Italy
| | - Jesús Pino
- SERGAS, Division of Orthopaedics Surgery and Traumatology, Santiago University Clinical Hospital, 15706 Santiago de Compostela, Spain
| | - Juan J Gómez-Reino
- SERGAS, Research Laboratory 9, NEIRID Lab (Neuroendocrine Interactions in Rheumatology and Inflammatory Diseases), Institute of Medical Research (IDIS), Santiago University Clinical Hospital, 15706 Santiago de Compostela, Spain
| | - Oreste Gualillo
- SERGAS, Research Laboratory 9, NEIRID Lab (Neuroendocrine Interactions in Rheumatology and Inflammatory Diseases), Institute of Medical Research (IDIS), Santiago University Clinical Hospital, 15706 Santiago de Compostela, Spain
| |
Collapse
|
|
49
|
Perruccio AV, Mahomed NN, Chandran V, Gandhi R. Plasma Adipokine Levels and Their Association with Overall Burden of Painful Joints among Individuals with Hip and Knee Osteoarthritis. J Rheumatol 2013; 41:334-7. [DOI: 10.3899/jrheum.130709] [Citation(s) in RCA: 47] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
Objective.To investigate the association between plasma adipokine levels and the burden of painful joints among individuals with hip and knee osteoarthritis (OA).Methods.Adipokines (leptin, adiponectin, adipsin, resistin) were determined by ELISA (n = 78). Individuals reported painful joints on a homunculus. Associations were examined by sex-stratified Poisson analyses.Results.Adjusted for age, body mass index, and hip/knee OA, higher leptin and adiponectin and lower adipsin levels were associated with greater painful joint burden (i.e., counts) among women (p < 0.01). Among men, higher resistin levels were associated with lower counts (p = 0.03).Conclusion.Findings support the likelihood of a systemic-dependent sex-specific pain burden among individuals with OA.
Collapse
|
|
50
|
Salih S, Sutton P. Obesity, knee osteoarthritis and knee arthroplasty: a review. Sports Med Arthrosc Rehabil Ther Technol 2013; 5:25. [PMID: 24304704 PMCID: PMC3879025 DOI: 10.1186/2052-1847-5-25] [Citation(s) in RCA: 42] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2013] [Accepted: 11/24/2013] [Indexed: 12/22/2022]
Abstract
The incidence of obesity is rising worldwide. Obesity is a risk factor for developing osteoarthritis in the knee. Obesity and knee osteoarthritis are independently disabling conditions and in combination pose difficult therapeutic challenges. This review will discuss obesity, osteoarthritis, and the problems associated with knee osteoarthritis in an obese population. Treatment options including surgery and its success will be discussed.
Collapse
Affiliation(s)
- Saif Salih
- Department of Trauma and Orthopaedics, Northern General Hospital, Herries Rd, Sheffield S5 7 AU, UK.
| | | |
Collapse
|