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Hasvik E, Haugen AJ, Grøvle L. Clinical characteristics of patients with bone marrow edema syndrome, transient osteoporosis or migratory osteoporosis: a scoping review. Bone 2025; 198:117535. [PMID: 40389186 DOI: 10.1016/j.bone.2025.117535] [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: 11/17/2024] [Revised: 05/06/2025] [Accepted: 05/16/2025] [Indexed: 05/21/2025]
Abstract
Bone marrow edema syndrome (BMES), transient osteoporosis of the hip (TOH), and regional migratory osteoporosis (RMO), along with numerous variants of these terms, are used inconsistently to describe spontaneous pain, typically in the lower extremity, accompanied by bone marrow edema on MRI and/or bone demineralization. In the present review, we aimed to determine whether these designations represent distinct conditions or varying manifestations of a shared pathology. We employed a scoping review methodology, following a preregistered protocol, utilizing a comprehensive systematic search of electronic databases. Eligible publications reported on patients designated with BMES, TOH, RMO, or related terms. A total of 2924 patients, across 561 studies, were included. Data extraction focused on demographics, clinical features and imaging results. Descriptive statistics and meta-analytic methods were used to synthesize the data. Our results show that patients described by terms related to bone marrow edema syndrome, or transient or migratory osteoporosis, displayed similar demographic and clinical profiles. Our findings strongly suggest that these various designations refer to the same clinical entity. Bone marrow edema syndrome appears to be the most suitable term to describe this condition, facilitating a more standardized approach to future diagnosis, management and research.
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Affiliation(s)
- Eivind Hasvik
- Dept. of Physical Medicine and Rehabilitation, Østfold Hospital Trust, Norway.
| | | | - Lars Grøvle
- Dept. of Rheumatology, Østfold Hospital Trust, Norway
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Liu J, Ji F, Lee H, Kim JH. Association between the appendicular skeletal muscle mass-to-visceral fat area ratio and bone mineral density and osteoporosis: A cross-sectional study. Exp Gerontol 2025; 206:112772. [PMID: 40339765 DOI: 10.1016/j.exger.2025.112772] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2025] [Revised: 04/28/2025] [Accepted: 05/01/2025] [Indexed: 05/10/2025]
Abstract
OBJECTIVE This cross-sectional study investigated the association between appendicular skeletal muscle mass-to-visceral fat area ratio (SVR), bone mineral density (BMD), and osteoporosis in U.S. adults using NHANES data. METHODS Data from the 2013-2014 and 2017-2018 NHANES cycles were analyzed. Multivariable regression models assessed associations between SVR, BMD, and osteoporosis, adjusting for demographic, lifestyle, metabolic, and comorbidity variables. Generalized Additive Models with smooth curve fitting and likelihood ratio tests evaluated model fit. Subgroup analyses explored effect modifications. RESULTS The study included 2325 individuals with a mean age of 50.66 ± 5.55 years. In fully adjusted models, the highest SVR tertile was associated with a 0.05 g/cm2 higher BMD (β = 0.05, 95 % CI: 0.03-0.08, P = 0.002) and 57 % lower odds of osteoporosis (OR = 0.43, 95 % CI: 0.24-0.78, P = 0.028) than the lowest tertile. As a continuous variable, SVR remained significantly associated with BMD (β = 0.03, 95 % CI: 0.02-0.04, P = 0.002) and osteoporosis (OR = 0.67, 95 % CI: 0.50-0.91, P = 0.033). Stronger associations were found in individuals with diabetes (β = 0.09, 95 % CI: 0.06-0.12, P < 0.01) and BMI ≥ 30 (β = 0.07, 95 % CI: 0.05-0.09, P < 0.01). CONCLUSION Higher SVR was significantly associated with increased BMD and lower odds of osteoporosis, suggesting its potential as a marker for bone health assessment. However, the cross-sectional design limits causal inference. Further longitudinal and mechanistic studies are warranted to confirm these findings and explore clinical applicability.
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Affiliation(s)
- Jiao Liu
- Major in Sport Science, Division of Sport Industry and Science, College of Performing Arts and Sport, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul 04763, Republic of Korea
| | - Fujue Ji
- Major in Sport Science, Division of Sport Industry and Science, College of Performing Arts and Sport, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul 04763, Republic of Korea; BK21 FOUR Human-Tech Convergence Program, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, 004763, Republic of Korea
| | - Haesung Lee
- Major in Sport Science, Division of Sport Industry and Science, College of Performing Arts and Sport, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul 04763, Republic of Korea; BK21 FOUR Human-Tech Convergence Program, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, 004763, Republic of Korea
| | - Jong-Hee Kim
- Major in Sport Science, Division of Sport Industry and Science, College of Performing Arts and Sport, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul 04763, Republic of Korea; BK21 FOUR Human-Tech Convergence Program, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, 004763, Republic of Korea.
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Uemura K, Kono S, Takashima K, Tamura K, Higuchi R, Mae H, Nakamura N, Otake Y, Sato Y, Sugano N, Okada S, Hamada H. Side-to-side differences in hip bone mineral density in patients with unilateral hip osteoarthritis. Bone 2025; 195:117456. [PMID: 40068796 DOI: 10.1016/j.bone.2025.117456] [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: 01/11/2025] [Revised: 02/18/2025] [Accepted: 03/08/2025] [Indexed: 04/11/2025]
Abstract
BACKGROUND Accurately evaluating bone mineral density (BMD) in patients with unilateral hip osteoarthritis (OA) is crucial for diagnosing osteoporosis and selecting implants for hip arthroplasty. Our goal was to measure the BMD differences between sides, examine contributing factors, and identify the optimal side for BMD assessment in these patients. METHODS We analyzed 108 women with unilateral hip OA. Bilateral hip BMD was assessed automatically through quantitative CT (QCT) utilizing a validated, deep-learning-based approach. We evaluated BMD variations between the OA and healthy hips across total, neck, and distal regions. To determine their contributions, we analyzed factors, including patient demographics, Crowe classification, Bombelli classification, knee OA status, hip functional score, and gluteal muscle volume and density. Furthermore, we examined how side-to-side BMD differences influenced osteoporosis diagnosis using T-scores based on QCT. RESULTS The average BMD on the OA side was 6.9 % lower in the total region, 14.5 % higher in the neck region, and 9.4 % lower in the distal region than on the healthy side. Contributing factors to the reduced BMD in the OA hip included younger age, Bombelli classification (atrophic type), and significant gluteal muscle atrophy. Diagnoses from the OA side revealed lower sensitivity (61 %) than those from the healthy side (88 %). CONCLUSIONS Analysis on one side alone yields a more precise osteoporosis diagnosis from the healthy side. Nonetheless, bilateral BMD assessment remains crucial, particularly in younger individuals and those with atrophic OA types. Although based on QCT, our findings support bilateral analysis by dual-energy X-ray absorptiometry for these patients.
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Affiliation(s)
- Keisuke Uemura
- Department of Orthopaedic Medical Engineering, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
| | - Sotaro Kono
- Department of Orthopaedic Surgery, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
| | - Kazuma Takashima
- Department of Orthopaedic Surgery, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
| | - Kazunori Tamura
- Department of Orthopaedics, Kyowakai hospital, Suita, Osaka, Japan
| | - Ryo Higuchi
- Department of Orthopaedic Surgery, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
| | - Hirokazu Mae
- Department of Orthopaedic Surgery, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
| | - Nobuo Nakamura
- Department of Orthopaedics, Kyowakai hospital, Suita, Osaka, Japan
| | - Yoshito Otake
- Division of Information Science, Graduate School of Science and Technology, Nara Institute of Science and Technology, Ikoma, Nara, Japan
| | - Yoshinobu Sato
- Division of Information Science, Graduate School of Science and Technology, Nara Institute of Science and Technology, Ikoma, Nara, Japan
| | - Nobuhiko Sugano
- Department of Orthopaedic Medical Engineering, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
| | - Seiji Okada
- Department of Orthopaedic Surgery, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
| | - Hidetoshi Hamada
- Department of Orthopaedic Medical Engineering, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
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Albrecht AP, Kistler-Fischbacher M, De Godoi Rezende Costa Molino C, Armbrecht G, Freystaetter G, Theiler R, Kressig RW, Da Silva JAP, Rizzoli R, Wanner GA, Egli A, Dawson-Hughes B, Bischoff-Ferrari HA. Prevalence and incidence of osteoporotic vertebral fractures in community-dwelling European older adults: an observational analysis of the DO-HEALTH trial. Osteoporos Int 2025; 36:1077-1088. [PMID: 40278864 PMCID: PMC12122559 DOI: 10.1007/s00198-025-07489-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/21/2025] [Accepted: 04/01/2025] [Indexed: 04/26/2025]
Abstract
We examined vertebral fracture (VF) prevalence, incidence, and treatment among 1488 older adults. VF prevalence and incidence were higher in women, older participants, and those with low bone density. In addition to VFs being underdiagnosed (only 20.7% of VFs clinically recognized), treatment rates were low, underscoring the need for improved screening and management. PURPOSE To estimate prevalence and incidence of osteoporotic VFs and VF progressions overall and by sex, age, and bone status and to describe the proportion of participants with VFs in reporting osteoporosis (OP) medication use. METHODS This observational analysis of the DO-HEALTH trial, a three-year, randomized, controlled trial among community-dwelling adults age ≥ 70 years, includes a subsample of participants recruited at four study sites equipped with DXA machines. Prevalence and incidence rates (IR) of VFs and VF progressions were described overall and by subgroups of sex, age, and bone status. Incidence of VFs which were clinically recognized was also estimated. Further, we estimated the proportion of participants on OP medication. RESULTS A total of 1488 participants were included (mean age 74.9 years, 63.1% women, 77.0% had osteopenia or osteoporosis). One hundred forty-four (9.7%) participants had at least one radiographic VF at baseline and of those 19.4% participants reported OP medication use. Over the three-year follow-up, 50 participants sustained 58 new radiographic VFs (IR 1.4, 95% CI 1.1, 1.9). Of the 58 radiographic VFs, only 12 (20.7%) were clinically recognized. Furthermore, 31 participants sustained 35 VF progressions (N = 157; IR 7.7, 95% CI 5.5, 10.7). Prevalence and incidence were significantly higher in women, in older participants and those with osteopenia or osteoporosis compared to those with normal bone density. CONCLUSIONS This study suggests a high prevalence and incidence of VFs in community-dwelling European older adults. Underdiagnosis may be even more prevalent than previously observed, and treatment rates were low.
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Affiliation(s)
- Andreas P Albrecht
- Department of Aging Medicine and Aging Research, University of Zurich, Zurich, Switzerland
- Centre On Aging and Mobility, University of Zurich, Zurich, Switzerland
| | - Melanie Kistler-Fischbacher
- Department of Aging Medicine and Aging Research, University of Zurich, Zurich, Switzerland
- Centre On Aging and Mobility, University of Zurich, Zurich, Switzerland
| | - Caroline De Godoi Rezende Costa Molino
- Department of Aging Medicine and Aging Research, University of Zurich, Zurich, Switzerland
- Centre On Aging and Mobility, University of Zurich, Zurich, Switzerland
| | - Gabriele Armbrecht
- Department of Radiology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität Zu Berlin, Berlin, Germany
| | - Gregor Freystaetter
- Centre On Aging and Mobility, University of Zurich, Zurich, Switzerland
- University Clinic for Aging Medicine, Zurich City Hospital, Zurich, Switzerland
| | - Robert Theiler
- Centre On Aging and Mobility, University of Zurich, Zurich, Switzerland
| | - Reto W Kressig
- Dept. of Aging Medicine FELIX PLATTER, University of Basel, Basel, Switzerland
- Faculty of Medicine, University of Basel, Basel, Switzerland
| | - Jose A P Da Silva
- Centro Hospitalar E Universitário de Coimbra, Coimbra, Portugal
- Faculty of Medicine, Coimbra Institute for Clinical and Biomedical Research (iCBR), University of Coimbra, Coimbra, Portugal
| | - René Rizzoli
- Division of Bone Diseases, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland
| | - Guido A Wanner
- Spine Clinic and Traumatology, Private Hospital Bethanien, Zurich, Switzerland
| | - Andreas Egli
- Department of Aging Medicine and Aging Research, University of Zurich, Zurich, Switzerland
- Centre On Aging and Mobility, University of Zurich, Zurich, Switzerland
| | - Bess Dawson-Hughes
- Jean Mayer USDA Human Nutrition Research Center On Aging, Tufts University, Boston, MA, USA
| | - Heike A Bischoff-Ferrari
- Department of Aging Medicine and Aging Research, University of Zurich, Zurich, Switzerland.
- Centre On Aging and Mobility, University of Zurich, Zurich, Switzerland.
- Dept. of Aging Medicine FELIX PLATTER, University of Basel, Basel, Switzerland.
- Faculty of Medicine, University of Basel, Basel, Switzerland.
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Wei Y, Li D, Wang M, Li G, Liu F, Liu X, Wang S, Wang L. Diagnostic value of 99mTc-MDP single-photon emission computed tomography/computed tomography in medication-related osteonecrosis of the jaw: A single-center retrospective study of 39 patients. JOURNAL OF STOMATOLOGY, ORAL AND MAXILLOFACIAL SURGERY 2025; 126:102262. [PMID: 39855303 DOI: 10.1016/j.jormas.2025.102262] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/17/2024] [Revised: 01/13/2025] [Accepted: 01/22/2025] [Indexed: 01/27/2025]
Abstract
OBJECTIVE The focus of this study was to assess the diagnostic effectiveness of 99mTc-MDP single-photon emission computed tomography/computed tomography (SPECT/CT) in pinpointing medication-related osteonecrosis of the jaw (MRONJ). METHODS We gathered a total of 39 patients who were suspected of having MRONJ and displayed radionuclide concentration in the jaws on whole-body bone scans. These patients were subjected to simultaneous SPECT/CT fusion imaging of the jaws during delayed imaging. A consistent team of nuclear medicine physicians and oral and maxillofacial surgeons carried out diagnostic evaluations using SPECT/CT image analysis and dental specialist examinations, and the diagnoses were documented. RESULTS Based on the SPECT/CT image analysis and dental specialist examination outcomes, we calculated the sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of 99mTc-MDP SPECT/CT in diagnosing suspected MRONJ. Further, we enumerated the number and proportion of patients at each stage. CONCLUSION Our findings suggest that 99mTc-MDP SPECT/CT demonstrates high diagnostic precision in patients suspected of MRONJ who display radionuclide concentration in the jaw on whole-body bone scans. Moreover, it proves beneficial in identifying the early stages of MRONJ.
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Affiliation(s)
- Yubo Wei
- Department of Oral & Maxillofacial Surgery, the Affiliated Hospital of Qingdao University, Shandong Province, Qingdao 266000, China; School of Stomatology, Qingdao University, Shandong Province, Qingdao 266000, China
| | - Dongpo Li
- Department of Oral & Maxillofacial Surgery, the Affiliated Hospital of Qingdao University, Shandong Province, Qingdao 266000, China; School of Stomatology, Qingdao University, Shandong Province, Qingdao 266000, China
| | - Meng Wang
- Department of Oral & Maxillofacial Surgery, the Affiliated Hospital of Qingdao University, Shandong Province, Qingdao 266000, China; School of Stomatology, Qingdao University, Shandong Province, Qingdao 266000, China
| | - Guoliang Li
- Department of Radiation Oncology, Affiliated Hospital of Qingdao University, Qingdao 266000, Shandong, China
| | - Fengzhi Liu
- School of Stomatology, Qingdao University, Shandong Province, Qingdao 266000, China; Department of Stomatology, Affiliated Hospital of Qingdao University, Qingdao 266000, Shandong, China
| | - Xinfeng Liu
- Department of Nuclear Medicine, Affiliated Hospital of Qingdao University, Qingdao 266000, Shandong, China
| | - Shuangyi Wang
- Department of Oral & Maxillofacial Surgery, the Affiliated Hospital of Qingdao University, Shandong Province, Qingdao 266000, China; School of Stomatology, Qingdao University, Shandong Province, Qingdao 266000, China.
| | - Lin Wang
- Department of Oral & Maxillofacial Surgery, the Affiliated Hospital of Qingdao University, Shandong Province, Qingdao 266000, China; School of Stomatology, Qingdao University, Shandong Province, Qingdao 266000, China.
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Ma Y, Zou X, Jian Q, Dong J, Huang X, Zhai Y, Qian L. A-485 alleviates postmenopausal osteoporosis by activating GLUD1 deacetylation through the SENP1-Sirt3 signal pathway. J Orthop Surg Res 2025; 20:542. [PMID: 40442713 PMCID: PMC12121107 DOI: 10.1186/s13018-025-05839-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2025] [Accepted: 04/22/2025] [Indexed: 06/02/2025] Open
Abstract
OBJECTIVE Postmenopausal osteoporosis (OP) is a bone disease caused by estrogen deficiency. A-485 is a selective inhibitor of p300/CBP histone acetyltransferase (HAT) with potential regulatory effects on bone remodeling. This study aims to investigate the effects of A-485 on postmenopausal OP and its underlying mechanisms. METHODS For animal experiments, 61 female Wistar rats were used to establish an OP model through ovariectomy (OVX). The rats were administered with A-485 (100 mg/kg/day) via intraperitoneal injection for six weeks. Bone mineral density (BMD) was measured using dual-energy X-ray absorptiometry (DXA). Histopathological changes were observed using HE and Masson's trichrome staining. ELISA was used to measure bone resorption markers (CTX-1, DPD) and the bone formation marker (P1NP) in rats. Osteoblast differentiation markers (Runx2, OCN), SENP1, Sirt3 expression levels, and GLUD1 acetylation were assessed via Western blot (WB) and RT-qPCR. In vitro, MC3T3-E1 osteogenic progenitor cells were cultured in osteogenic differentiation medium supplemented with ascorbic acid, β-glycerophosphate, dexamethasone, and fulvestrant. CCK-8 was performed to evaluate cell proliferation. Flow cytometry was selected to measure apoptosis and mitochondrial membrane potential. WB and RT-qPCR were employed to analyze ERα, ERβ, Runx2, Sirt3, and GLUD1 acetylation. Additionally, Alizarin red staining was applied to monitor osteoblast mineralization. ATP levels were detected using a commercial kit, and ROS levels were measured by MitoSOX Red. RESULTS In vivo, ovariectomized rats exhibited lower BMD, impaired bone trabeculae, increased CTX-1 and DPD, and altered expression of Runx2 and OCN, all of which were reversed by A-485 treatment. In vitro, A-485 activated GLUD1 deacetylation, enhanced osteogenic differentiation, and improved mitochondrial function. Regarding the mechanism, A-485 activated the SENP1-Sirt3 signal pathway, with SENP1 knockdown negating the effects of A-485. In vivo, A-485 reduced GLUD1 acetylation and promoted improvement of OP, which were reversed by SENP1 knockdown. CONCLUSION A-485 ameliorates postmenopausal OP by activating GLUD1 deacetylation via the SENP1-Sirt3 signal pathway, thus improving mitochondrial function, and promoting osteogenic differentiation and mineralization.
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Affiliation(s)
- Yinghong Ma
- College of Anesthesia, Guizhou Medical University, Guiyang, Guizhou, 550000, China
- Department of Pain Medicine, Beijing Jishuitan Hospital Guizhou Hospital, Guiyang, Guizhou, 550000, China
| | - Xiaohua Zou
- College of Anesthesia, Guizhou Medical University, Guiyang, Guizhou, 550000, China.
- Department of Anesthesiology, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, 550000, China.
- , No. 28 Guiyi Street, Yunyan District, Guiyang City, Guizhou Province, China.
| | - Qianhong Jian
- Department of Pain Medicine, Beijing Jishuitan Hospital Guizhou Hospital, Guiyang, Guizhou, 550000, China
| | - Jiaxin Dong
- Department of Pain Medicine, Beijing Jishuitan Hospital Guizhou Hospital, Guiyang, Guizhou, 550000, China
| | - Xianbing Huang
- Department of Pain Medicine, Beijing Jishuitan Hospital Guizhou Hospital, Guiyang, Guizhou, 550000, China
| | - Yue Zhai
- Department of Pain Medicine, Beijing Jishuitan Hospital Guizhou Hospital, Guiyang, Guizhou, 550000, China
| | - Li Qian
- Department of Pain Medicine, Beijing Jishuitan Hospital Guizhou Hospital, Guiyang, Guizhou, 550000, China.
- , 123 Shachong South Road, Nanming District, Guiyang City, Guizhou Province, China.
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Dai X, Liu C, Bi W, Zheng G, Lv K, Xia Z. Estradiol and vitamin D exert a synergistic effect on preventing osteoporosis via the miR-351-5p/IRS1 axis and mTOR/NFκB signaling pathway. Sci Rep 2025; 15:18678. [PMID: 40436926 PMCID: PMC12119810 DOI: 10.1038/s41598-025-02808-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2025] [Accepted: 05/15/2025] [Indexed: 06/01/2025] Open
Abstract
This study aimed to investigate the antiosteoporotic effects and regulatory mechanisms of estradiol (E2) and vitamin D. MC3T3-E1 cells were treated with E2, vitamin D, or their combination, followed by a systematic assessment of cell proliferation and osteogenic differentiation capacity across the treatment groups. Subsequently, miRNA sequencing was performed to analyze differentially expressed miRNAs between the control and E2&vitamin D groups. The target relationship between miR-351-5p and IRS1 was validated, and the effects of the miR-351-5p/IRS1 axis on osteogenesis and mTOR/NFκB signaling pathway were determined after combination treatment. Additionally, an ovariectomized (OVX) osteoporosis mouse model was established to systematically examine the effects of E2, vitamin D, and their combination on osteoporosis and mTOR/NFκB signaling pathway. E2 and vitamin D synergistically promoted MC3T3-E1 cell proliferation and osteogenic differentiation. miR-351-5p was identified through miRNA sequencing analysis. miR-351-5p was downregulated in MC3T3-E1 cells after E2 and vitamin D combination treatment, and its overexpression partially reversed the effect of the combination treatment on osteogenesis. IRS1 was a target of miR-351-5p. When overexpressed, IRS1 partially mitigated the impact of miR-351-5p overexpression on osteogenesis and mTOR/NFκB signaling pathway under the combination treatment. Furthermore, in vivo experiments demonstrated that E2 and vitamin D could synergistically prevent osteoporosis in OVX mice by inhibiting the mTOR/NFκB signaling pathway. In conclusion, E2 and vitamin D exhibited a synergistic effect in preventing osteoporosis through the miR-351-5p/IRS1 axis and mTOR/NFκB signaling pathway. E2 and vitamin D combination treatment could be a potential anti-osteoporotic strategy for osteoporosis treatment.
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Affiliation(s)
- Xiaoyan Dai
- Department of Otolaryngology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
| | - Changcun Liu
- Department of Nuclear Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, P.R. China
| | - Wenkai Bi
- Department of Nuclear Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
| | - Guiwen Zheng
- Department of Nuclear Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
| | - Kuan Lv
- Department of Nuclear Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
| | - Zhiming Xia
- Department of Nuclear Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China.
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van Veelen NM, Horvat M, Link BC, van de Wall BJM, Beeres FJP. Locking pegs versus locking screws in volar plating of distal radius fractures. Eur J Trauma Emerg Surg 2025; 51:217. [PMID: 40404837 PMCID: PMC12098432 DOI: 10.1007/s00068-025-02876-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2025] [Accepted: 04/27/2025] [Indexed: 05/24/2025]
Abstract
PURPOSE The aim of this study was to compare the radiological outcome of patients with distal radius fractures stabilized with a volar plate using either locking screws or pegs. MATERIAL & METHODS For this retrospective study all adult patients that received volar plating of a distal radius fracture at a trauma center between 06/2019 and 06/2022 were eligible for inclusion. Only patients who received an implant allowing both locking pegs and screws were included. Primary outcome was radiological loss of reduction at the 6-week and at the 12-month follow-up. Secondary outcomes were duration of surgery, implant removal, fracture union and complications. RESULTS Fourty-nine patients treated with pegs and 39 with screws were included. Patient demographics were comparable, however there were more complex fractures in the peg group. There was no significant difference in the occurrence of radiological loss of reduction between the groups at 6 weeks or 12 months (p = 1). Patients treated with pegs were more frequently operated upon by experienced surgeons while screws were more often used by more junior staff. The duration of surgery was longer for patients who received screws (p = 0.003). Union was achieved in all fractures for which a 12-month x-ray was available. There was no significant difference in implant removal rate or other complications. CONCLUSIONS Regarding secondary loss of reduction both locking pegs and screws show similar results. Considering the potential benefits of pegs, such as the smooth surface which may reduce the risk of joint penetration, pegs are a viable alternative to screws.
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Affiliation(s)
- Nicole M van Veelen
- Department of Orthopaedic and Trauma Surgery, Luzerner Kantonsspital, Spitalstrasse 166000, Lucerne, Switzerland.
| | - Matija Horvat
- Department of Orthopaedic and Trauma Surgery, Luzerner Kantonsspital, Spitalstrasse 166000, Lucerne, Switzerland
| | - Björn-Christian Link
- Department of Orthopaedic and Trauma Surgery, Luzerner Kantonsspital, Spitalstrasse 166000, Lucerne, Switzerland
| | - Bryan J M van de Wall
- Department of Orthopaedic and Trauma Surgery, Luzerner Kantonsspital, Spitalstrasse 166000, Lucerne, Switzerland
- Faculty of Health Sciences and Medicine, University of Lucerne, Alpenquai 4, 6005, Lucerne, Switzerland
| | - Frank J P Beeres
- Department of Orthopaedic and Trauma Surgery, Luzerner Kantonsspital, Spitalstrasse 166000, Lucerne, Switzerland
- Faculty of Health Sciences and Medicine, University of Lucerne, Alpenquai 4, 6005, Lucerne, Switzerland
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9
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Kluijver LG, Wagenmakers MAEM, Wilson JHP, Langendonk JG. The Impact of Minimal Sunlight Exposure on Bone Health: Insights From a Cohort Study in Erythropoietic Protoporphyria. J Clin Endocrinol Metab 2025; 110:1633-1646. [PMID: 39401412 DOI: 10.1210/clinem/dgae729] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/30/2024] [Indexed: 05/20/2025]
Abstract
CONTEXT Erythropoietic protoporphyria (EPP) is a rare inherited metabolic disease, causing lifelong painful phototoxic reactions, minimal sunlight exposure, and vitamin D deficiency. Previous studies reported a high osteoporosis prevalence in EPP patients. OBJECTIVE To identify those at risk for low bone mineral density (BMD) and assess which factors, including treatment with cholecalciferol and afamelanotide, improve BMD in EPP. METHODS A longitudinal ambispective single-center cohort study. Data from patient files and two-time questionnaires from adult patients with EPP who underwent at least one dual-energy x-ray absorptiometry (DXA) scan between 2012 and 2023 were used. RESULTS BMD is low in EPP patients, with 82.7% of the 139 patients having a Z-score below 0 SD at baseline. Low BMD classified as osteopenia was found in 39.5%, and osteoporosis in 15.3%. There were 50 osteoporosis-related fractures in 34.2% of patients. Aging (odds ratio [OR] 1.08; CI, 1.03-1.12), persistent vitamin D deficiency (OR 1.11; 95% CI, 1.00-1.23) and a low body mass index (OR 0.91; 95% CI, 0.82-0.99) increased the odds of low BMD. Patients with a vitamin D deficiency (OR 5.51; 95% CI, 1.69-17.92) and no cholecalciferol at baseline (OR 0.22; 95% CI, 0.04-1.34) had the highest odds of improving their BMD. Afamelanotide did not improve BMD. CONCLUSION 25-hydroxyvitamin D (25(OH)D) status plays a crucial role in both preventing low BMD and improving BMD. EPP is a natural model for lack of sunlight exposure and vitamin D deficiency, underlining the importance of lifelong adequate vitamin D status for bone health in the general population.
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Affiliation(s)
- Louisa G Kluijver
- Porphyria Center Rotterdam, Center for Lysosomal and Metabolic Disease, Department of Internal Medicine, Erasmus MC, Erasmus University Medical Center, 3000 WB, Rotterdam, The Netherlands
| | - Margreet A E M Wagenmakers
- Porphyria Center Rotterdam, Center for Lysosomal and Metabolic Disease, Department of Internal Medicine, Erasmus MC, Erasmus University Medical Center, 3000 WB, Rotterdam, The Netherlands
| | - J H Paul Wilson
- Porphyria Center Rotterdam, Center for Lysosomal and Metabolic Disease, Department of Internal Medicine, Erasmus MC, Erasmus University Medical Center, 3000 WB, Rotterdam, The Netherlands
| | - Janneke G Langendonk
- Porphyria Center Rotterdam, Center for Lysosomal and Metabolic Disease, Department of Internal Medicine, Erasmus MC, Erasmus University Medical Center, 3000 WB, Rotterdam, The Netherlands
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10
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Makras P, Erickson D, Davidge-Pitts CJ, Diamond EL, Allen CE, McClain KL, Abeykoon JP, Go RS, Siwakoti K, Sotoudeh H, Ravindran A, Gruber LM, Goyal G. Approach to the Patient: From Endocrinopathy to the Diagnosis of a Histiocytic Disorder. J Clin Endocrinol Metab 2025; 110:1756-1766. [PMID: 39699236 DOI: 10.1210/clinem/dgae827] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/26/2024] [Indexed: 12/20/2024]
Abstract
Endocrinopathies are frequently the initial presentation of histiocytic neoplasms, which are rare hematologic disorders affecting multiple organ systems. Langerhans cell histiocytosis and Erdheim-Chester disease are 2 such disorders known to infiltrate the hypothalamus and/or pituitary gland, leading to arginine vasopressin deficiency (AVP-D) and anterior pituitary dysfunction (APD) in 20% to 30% of cases, often as the first manifestation. Conversely, histiocytic disorders account for a notable proportion (10-15%) of all pituitary stalk lesions. The diagnosis of histiocytoses is often delayed in such cases due to the nonspecific presentation of endocrinopathies and pituitary involvement. Consequently, endocrinologists are at the frontline and uniquely positioned to achieve early diagnosis by recognizing the varied nonendocrine features of these disorders. This article provides an overview of the endocrine manifestations of histiocytic disorders and presents a simplified algorithm to guide the diagnostic workup in cases presenting with "idiopathic" AVP-D or APD. Such cases should be evaluated for histiocytic neoplasms with additional imaging studies and biopsies of suspected disease sites. If no disease site beyond the pituitary is identified, the risks and benefits of a pituitary stalk lesion biopsy must be carefully considered. While treatments of histiocytic neoplasms are highly efficacious, endocrinopathies are considered permanent and require long-term hormone replacement. It remains unclear whether early diagnosis and novel targeted therapies can reverse these endocrine disorders. Therefore, the role of the endocrinologist role is critical in the diagnosis and management of these rare diseases.
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Affiliation(s)
- Polyzois Makras
- Department of Endocrinology and Diabetes and Department of Medical Research, LCH Adult Clinic, 251 Hellenic Air Force & VA General Hospital, Athens 11525, Greece
| | - Dana Erickson
- Division of Endocrinology, Diabetes, Metabolism and Nutrition, Mayo Clinic, Rochester, MN 55902, USA
| | - Caroline J Davidge-Pitts
- Division of Endocrinology, Diabetes, Metabolism and Nutrition, Mayo Clinic, Rochester, MN 55902, USA
| | - Eli L Diamond
- Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
| | - Carl E Allen
- Department of Pediatrics, Baylor College of Medicine and Texas Children's Cancer Center, Texas Children's Hospital, Houston, TX 77030, USA
| | - Kenneth L McClain
- Department of Pediatrics, Baylor College of Medicine and Texas Children's Cancer Center, Texas Children's Hospital, Houston, TX 77030, USA
| | | | - Ronald S Go
- Division of Hematology, Mayo Clinic, Rochester, MN 55902, USA
| | - Krishmita Siwakoti
- Division of Endocrinology, University of Alabama at Birmingham, Birmingham, AL 35233, USA
| | - Houman Sotoudeh
- Department of Radiology, University of Alabama at Birmingham, Birmingham, AL 35233, USA
| | - Aishwarya Ravindran
- Division of Laboratory Medicine-Hematopathology, Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35233, USA
| | - Lucinda M Gruber
- Division of Endocrinology, Diabetes, Metabolism and Nutrition, Mayo Clinic, Rochester, MN 55902, USA
| | - Gaurav Goyal
- Division of Hematology- Oncology, University of Alabama at Birmingham, Birmingham, AL 35233, USA
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Gu P, Shi B, Zhang Z, Du Y, Jia Y, Zhu G, Wen T, Jia Z, Wu Y, Zhao X. Association of visceral fat metabolic score with bone mineral density and osteoporosis: a NHANES cross-sectional study. JOURNAL OF HEALTH, POPULATION, AND NUTRITION 2025; 44:156. [PMID: 40369619 PMCID: PMC12079861 DOI: 10.1186/s41043-025-00914-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/28/2025] [Accepted: 05/03/2025] [Indexed: 05/16/2025]
Abstract
BACKGROUND Metabolic Score for Visceral Fat (METS-VF) is commonly used as an indicator for assessing visceral fat metabolism. However, the relationship between METS-VF, Bone Mineral Density (BMD), and osteoporosis remains unclear in the American population. METHODS This study utilized cross-sectional data from the National Health and Nutrition Examination Survey (NHANES), including participants aged 20 years and older, from the survey cycles conducted between 2005 and 2010, 2013-2014, and 2017-2018. Multivariable weighted linear regression and logistic regression analyses were first applied to investigate the associations between the METS-VF, femoral BMD, and osteoporosis. In addition, subgroup interaction analyses were performed to evaluate the robustness of these associations. To address potential non-linear relationships, restricted cubic spline regression was employed. All statistical analyses were conducted using R software version 4.3.3. P values were two-tailed, with P < 0.05 considered statistically significant. RESULTS After adjusting for all covariates, the positive correlations between METS-VF and BMD measurements at all sites remained statistically significant (p < 0.001 & p for trend < 0.001). Multivariable logistic regression analysis indicated that, after adjusting for covariates related to osteoporosis, each one-unit increase in METS-VF was associated with a 63.1% reduction in the risk of developing osteoporosis. Moreover, the direction of the associations between METS-VF and both BMD and osteoporosis remained consistent across all subgroups, while restricted cubic spline (RCS) analyses suggested nonlinear relationships. The 5.82-7.35 METS-VF range yielded a mean 51.9% osteoporosis risk reduction (sustained ≥ 30% peak efficacy in 66.7% of participants). CONCLUSIONS METS-VF demonstrated a nonlinear positive association with BMD and a nonlinear inverse relationship with osteoporosis risk. Future studies should establish optimal biological thresholds of METS-VF for skeletal health. CLINICAL TRIAL NUMBER Not applicable.
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Affiliation(s)
- Peng Gu
- Department of Orthopedics, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, 100700, China
- Clinical Medical School, Qinghai University, Xining, 810001, China
| | - Bowen Shi
- Department of Orthopedic Traumatology, Tianjin Hospital, Tianjin, 300200, China
| | - Zheng Zhang
- Department of Public Health, Qinghai University School of Medicine, Xining, 810008, China
| | - Ying Du
- Department of Orthopedics, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, 100700, China
| | - Yanqing Jia
- Department of Orthopedics, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, 100700, China
| | - Guowei Zhu
- The Centre Hospital of Jinzhou, Emergency Department, Jinzhou, 121000, China
| | - Tianlin Wen
- Department of Orthopedics, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, 100700, China
| | - Zhiwei Jia
- Department of Orthopedics, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, 100700, China.
| | - Yaohong Wu
- Department of Spine Surgery, Ganzhou People's Hospital, Ganzhou, 341000, China.
| | - Xiyan Zhao
- Department of Endocrinology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, 10053, China.
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12
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Ruotsalainen T, Panfilov E, Thevenot J, Tiulpin A, Saarakkala S, Niinimäki J, Lehenkari P, Valkealahti M. Total radius BMD correlates with the hip and lumbar spine BMD among post-menopausal patients with fragility wrist fracture in a machine learning model. Arch Osteoporos 2025; 20:66. [PMID: 40366492 DOI: 10.1007/s11657-025-01542-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/31/2024] [Accepted: 04/15/2025] [Indexed: 05/15/2025]
Abstract
Osteoporosis screening should be systematic in the group of over 50-year-old females with a radius fracture. We tested a phantom combined with machine learning model and studied osteoporosis-related variables. This machine learning model for screening osteoporosis using plain radiographs requires further investigation in larger cohorts to assess its potential as a replacement for DXA measurements in settings where DXA is not available. PURPOSE The main purpose of this study was to improve osteoporosis screening, especially in post-menopausal patients with fragility wrist fractures. The secondary objective was to increase understanding of the connection between osteoporosis and aging, as well as other risk factors. METHODS We collected data on 83 females > 50 years old with a distal radius fracture treated at Oulu University Hospital in 2019-2020. The data included basic patient information, WHO FRAX tool, blood tests, X-ray imaging of the fractured wrist, and DXA scanning of the non-fractured forearm, both hips, and the lumbar spine. Machine learning was used in combination with a custom phantom. RESULTS Eighty-five percent of the study population had osteopenia or osteoporosis. Only 28.4% of patients had increased bone resorption activity measured by ICTP values. Total radius BMD correlated with other osteoporosis-related variables (age r = - 0.494, BMI r = 0.273, FRAX osteoporotic fracture risk r = - 0.419, FRAX hip fracture risk r = - 0.433, hip BMD r = 0.435, and lumbar spine BMD r = 0.645), but the ultra distal (UD) radius BMD did not. Our custom phantom combined with a machine learning model showed potential for screening osteoporosis, with the class-wise accuracies for "Osteoporotic vs. osteopenic & normal bone" of 76% and 75%, respectively. CONCLUSION We suggest osteoporosis screening for all females over 50 years old with wrist fractures. We found that the total radius BMD correlates with the central BMD. Due to the limited sample size in the phantom and machine learning parts of the study, further research is needed to make a clinically useful tool for screening osteoporosis.
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Affiliation(s)
- Tapio Ruotsalainen
- Division of Musculoskeletal Surgery, University Hospital of Oulu, Oulu, Finland.
| | - Egor Panfilov
- Research Unit of Health Sciences and Technology, University of Oulu, Oulu, Finland
| | - Jerome Thevenot
- Research Unit of Health Sciences and Technology, University of Oulu, Oulu, Finland
| | - Aleksei Tiulpin
- Research Unit of Health Sciences and Technology, University of Oulu, Oulu, Finland
| | - Simo Saarakkala
- Research Unit of Health Sciences and Technology, University of Oulu, Oulu, Finland
| | - Jaakko Niinimäki
- Department of Diagnostic Radiology, Oulu University Hospital and Research Unit of Health Sciences and Technology, Medical Research Center Oulu, University of Oulu, Oulu, Finland
| | - Petri Lehenkari
- Division of Musculoskeletal Surgery, University Hospital of Oulu, Oulu, Finland
- Research Unit of Translational Medicine, Faculty of Medicine, University of Oulu, Oulu, Finland
| | - Maarit Valkealahti
- Division of Musculoskeletal Surgery, University Hospital of Oulu, Oulu, Finland
- Research Unit of Translational Medicine, Faculty of Medicine, University of Oulu, Oulu, Finland
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13
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Glynne S. Letter to the Editor. Menopause 2025:00042192-990000000-00454. [PMID: 40366377 DOI: 10.1097/gme.0000000000002582] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2025] [Accepted: 03/06/2025] [Indexed: 05/15/2025]
Affiliation(s)
- Sarah Glynne
- Claire Mellon & Associates, Department of Women's Health, The Portland Hospital, 205-209 Great Portland St, London W1W 5AH, UK
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Li W, Ye B, Meng S, Huang Z, Jiang X, Qie F, Liu Y, Shi X, Li M. The effect of Jintiange capsules on pain in patients with primary osteoporosis: a systematic review and meta-analysis. BMC Musculoskelet Disord 2025; 26:465. [PMID: 40361081 PMCID: PMC12070584 DOI: 10.1186/s12891-025-08694-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2024] [Accepted: 04/23/2025] [Indexed: 05/15/2025] Open
Abstract
BACKGROUND To evaluate the effectiveness of Jintiange capsules (JTG) in relieving pain in patients with primary osteoporosis (POP). METHODS A systematic review of the literature was conducted through seven databases, including PubMed, Web of Science, Cochrane Library, Embase, Chinese National Knowledge Infrastructure, Wanfang Database and SinoMed, from inception to October 2023. The control group was given conventional anti-osteoporosis drug therapy such as Alfacalcidol soft capsules, Alendronate sodium tablets, Caltrate D3, etc. The experimental group was treated with JTG alone or in combination with JTG on the basis of the drugs used in the control group. The primary outcome measure was the visual analog scale (VAS). Stata SE-64 software was used to conduct meta-analyses of the final included studies. RESULTS A total of 2916 participants were included in 21 articles. The results of meta-analysis showed that JTG relieved pain (WMD: -2.51; 95% CI: -3.30, -1.71; p < 0.05), improved the bone mineral density (BMD) of femoral neck (WMD: 0.83; 95% CI: 0.33, 1.33; p < 0.05) and lumbar (WMD: 1.14; 95% CI: 0.67, 1.62; p < 0.05), improved oswestry disability index (ODI) (WMD: -1.79; 95% CI: -3.05, -0.54; p < 0.05), enhanced timed up and go test (TUG) (WMD: -2.61; 95% CI: -4.60, -0.62; p < 0.05) and decreased fracture incidence (WMD: 0.37; 95% CI: 0.15, 0.93; p < 0.05). CONCLUSION In terms of relieving pain, improving BMD, improving activity function, and improving gait and preventing fracture, JTG is a good choice for patients with osteoporosis (OP).
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Affiliation(s)
- Wei Li
- Jiaxing Hospital of Traditional Chinese Medicine, Jiaxing, Zhejiang Province, China
- The Second School of Clinical Medicine, Zhejiang Chinese Medical University, Zhejiang Province, Hangzhou, China
| | - Baisheng Ye
- Shaoxing Shangyu Hospital of Traditional Chinese Medicine, Shaoxing, Zhejiang Province, China
- The Second School of Clinical Medicine, Zhejiang Chinese Medical University, Zhejiang Province, Hangzhou, China
| | - Shilong Meng
- The Second School of Clinical Medicine, Zhejiang Chinese Medical University, Zhejiang Province, Hangzhou, China
| | - Zhen Huang
- The Second School of Clinical Medicine, Zhejiang Chinese Medical University, Zhejiang Province, Hangzhou, China
| | - Xin Jiang
- The Second School of Clinical Medicine, Zhejiang Chinese Medical University, Zhejiang Province, Hangzhou, China
| | | | - Yaosheng Liu
- Department of Orthopedic Surgery, the Fifth Medical Center of PLA General Hospital, Beijing, China
| | - Xiaolin Shi
- The Second Affiliated Hospital of Zhejiang Chinese Medical University, Zhejiang Province, Hangzhou, China.
| | - Miaoer Li
- The Second Affiliated Hospital of Zhejiang Chinese Medical University, Zhejiang Province, Hangzhou, China.
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15
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Teng Z, Zhu J, Li K, Tong T, Li W, Chu H, Sun P. Efficacy and safety of acupuncture as an adjuvant therapy for osteoporosis: a systematic review and meta-analysis of randomized controlled trials. Front Endocrinol (Lausanne) 2025; 16:1561344. [PMID: 40416525 PMCID: PMC12098033 DOI: 10.3389/fendo.2025.1561344] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/15/2025] [Accepted: 04/16/2025] [Indexed: 05/27/2025] Open
Abstract
Objective To systematically evaluate the efficacy and safety of acupuncture as an adjuvant therapy for osteoporosis (OP) through a comprehensive synthesis of recent randomized controlled trial (RCT) evidence. Methods A systematic literature search was conducted across PubMed, Web of Science, CNKI, and Wanfang databases (2014 - 2024) to identify RCTs investigating acupuncture combined with conventional therapy for OP. Study quality was appraised using the Cochrane Risk of Bias tool, and meta-analyses were performed using RevMan 5.4 and Stata 15.0, with subgroup analyses stratified by intervention type, population characteristics, and treatment duration. Results 28 RCTs (n=2,758) were included. Meta-analysis revealed acupuncture significantly enhanced bone mineral density (BMD) versus controls: total (SMD = 0.47, p = 0.03), femoral neck (MD = 0.05, p = 0.01), lumbar spine (SMD = 0.40, p < 0.001), Ward's triangle (MD = 0.07, p = 0.02), and hip (SMD = 0.55, p < 0.001), with particularly marked improvements in the postmenopausal osteoporosis subgroup. Acupuncture demonstrated significant improvements in treatment efficacy, biochemical markers, pain scores, and symptom assessments, while reducing adverse events. Warm needle moxibustion outperformed controls in femoral neck (MD = 0.07, p = 0.002) and hip BMD (SMD = 0.87, p < 0.001), while electroacupuncture significantly elevated serum calcium (MD = 0.18, p = 0.02). Short-term interventions (≤ 3 months) demonstrated optimal efficacy. Conclusion Acupuncture demonstrates efficacy and safety as an OP adjuvant therapy. Current evidence is limited by regional bias and methodological heterogeneity. Multicenter, large-sample RCTs are needed to standardize protocols and validate long-term therapeutic efficacy. Systematic review registration https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42024499354.
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Affiliation(s)
- Zixin Teng
- Second Clinical Medical College of Anhui University of Traditional Chinese Medicine, Hefei, China
| | - Jingwei Zhu
- Second Clinical Medical College of Anhui University of Traditional Chinese Medicine, Hefei, China
| | - Kuiwu Li
- Second Clinical Medical College of Anhui University of Traditional Chinese Medicine, Hefei, China
| | - Tingting Tong
- Department of Encephalopathy, Second Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Hefei, China
| | - Wei Li
- Department of Encephalopathy, Second Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Hefei, China
| | - Haoran Chu
- Mingyi Hall, Second Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Hefei, China
| | - Peiyang Sun
- Department of Encephalopathy, Second Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Hefei, China
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Wu Y, Guo X, Jiang A, Bai J, Nie X. Estrogen regulates duodenal calcium absorption and improves postmenopausal osteoporosis by the effect of ERβ on PMCA1b. Sci Rep 2025; 15:16053. [PMID: 40341576 PMCID: PMC12062487 DOI: 10.1038/s41598-025-00605-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2024] [Accepted: 04/29/2025] [Indexed: 05/10/2025] Open
Abstract
Dietary calcium supplements can prevent osteoporosis, and our previous investigation demonstrated a notable increase in duodenal calcium absorption due to the impact of estrogen. The decrease of estrogen level in postmenopausal women is significantly associated with an increased incidence of osteoporosis. In this study, we further investigated the role of estrogen regulating duodenal calcium absorption in osteoporosis and elucidated its underlying molecular mechanism. We recruited ten young women in the prefollicular stage and ten menopausal women for the study. Furthermore, we performed trials on mice, as well as human duodenal epithelial cells and SCBN cells. The measurement of calcium absorption in the duodenum of mice was conducted through single-pass perfusion in vivo. We used a calcium imaging system to evaluate calcium absorption in SCBN cells. The bone mineral density was measured using small animal computed tomography and a bone densitometer. Furthermore, The expression levels of calcium transport proteins, namely plasma membrane calcium pump (PMCA1b) and transient receptor potential cation channel (TRPV6), were evaluated using western blot analysis. Compared to young women, postmenopausal women exhibited significant reductions in estrogen levels, bone mineral density, and the expression of PMCA1b and TRPV6 in duodenal mucosal tissues (P < 0.05). A positive correlation was also observed between estrogen levels, the expression of PMCA1b and TRPV6, and bone mineral density (P < 0.05). The estrogen levels, the expression of PMCA1b and TRPV6 in the duodenal mucosa, calcium absorptions, and bone mineral density were observed to be decreased in ovariectomized mice based on in vivo animal experiments (P < 0.05). However, estrogen upplementation can enhance duodenal calcium absorptions and ameliorate osteoporosis in ovariectomized mice, with its primary mechanism of action being the regulation of PMCA1b expression and function (P < 0.05). The findings from SCBN cells further confirm that estrogen enhances duodenal calcium absorption through the effect of ERβ on PMCA1b. Estrogen enhances the expression and functionality of PMCA1b in duodenal mucosal cells via ERβ, promoting duodenal calcium absorption and ameliorating postmenopausal osteoporosis.
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Affiliation(s)
- Yingyang Wu
- Department of Gastroenterology, The Second Affiliated Hospital of Army Medical University, Chongqing, China
| | - Xian Guo
- Department of Gastroenterology, The Second Affiliated Hospital of Army Medical University, Chongqing, China
| | - Airui Jiang
- Department of Gastroenterology, The Second Affiliated Hospital of Army Medical University, Chongqing, China
| | - Jianying Bai
- Department of Gastroenterology, The Second Affiliated Hospital of Army Medical University, Chongqing, China.
| | - Xubiao Nie
- Department of Gastroenterology, The Second Affiliated Hospital of Army Medical University, Chongqing, China.
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Liu E, Liu RY, Moraros J, McCloskey EV, Harvey NC, Lorentzon M, Johansson H, Kanis JA. Association between walking and hip fracture in women aged 65 and older: 20-year follow-up from the study of osteoporotic fractures. Osteoporos Int 2025:10.1007/s00198-025-07508-y. [PMID: 40332499 DOI: 10.1007/s00198-025-07508-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/20/2024] [Accepted: 04/24/2025] [Indexed: 05/08/2025]
Abstract
Hip fractures in elderly women pose significant healthcare challenges. Promoting walking for exercise as a cost-effective intervention may help reduce the risk of fractures in this population. PURPOSE This study aimed to examine the relationship between walking and hip fracture risk among women aged 65 years and older. METHODS A 20-year prospective study (1986-2006) included 9704 women from the Study of Osteoporotic Fractures (SOF) in the USA. Participants were followed biennially, and walking exposure was assessed by the number of city blocks walked for exercise, routine activity, and total blocks walked daily. Cox regression models with time-varying covariates assessed associations, with competing risks addressed using Fine and Gray models. Penalized splines were used to explore dose-response relationships. RESULTS In total, 1419 hip fractures were identified through the study period. The mean and median follow-up times for hip fractures or censoring were 15.0 and 15.8 years in the walking for exercise group, vs. 13.2 and 13.7 years in the not walking for exercise group. The hip fracture incidence rate was 10.0 cases per 1000 person-years (py) in the walking for exercise group compared to 10.9 per 1000 py in the not walking for exercise group. All-cause mortality was 37.1 per 1000 py in the walking for exercise group compared to 46.4 per 1000 py in the not walking for exercise group. Adjusted models showed that walking for exercise significantly reduced hip fracture risk (HR, 0.864; 95% CI, 0.762-0.980; P = 0.0230), with each additional block walked for exercise reducing risk (HR per block, 0.986; 95% CI, 0.978-0.995; P = 0.0022). Walking for routine activities showed no significant association. Spline analysis indicated walking 16 blocks (≈3200 steps) daily significantly lowered hip fracture risk. CONCLUSION Walking for exercise is linked to a reduced risk of hip fractures in elderly women. Walking the equivalent of 16 blocks or more (> 3200 steps) per day might be an effective way to reduce the risk of hip fractures in this vulnerable population.
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Affiliation(s)
- Enwu Liu
- College of Medicine and Public Health, Flinders University, Adelaide, Australia.
| | - Ryan Yan Liu
- College of Medicine and Public Health, Flinders University, Adelaide, Australia
| | - John Moraros
- School of Science, Suzhou Municipal Key Lab of AI4Health, Xi'an Jiaotong-Liverpool University, Suzhou, China
| | - Eugene V McCloskey
- Division of Clinical Medicine, School of Medicine & Population Health, Versus Arthritis Centre for Integrated Research in Musculoskeletal Ageing, University of Sheffield, Sheffield, UK
| | - Nicholas C Harvey
- MRC Lifecourse Epidemiology Centre, University of Southampton, Southampton, UK
- NIHR Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, UK
| | - Mattias Lorentzon
- Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Osteoporosis Centre, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
- Geriatric Medicine, Region Västra Götaland, Sahlgrenska University Hospital, Mölndal, Sweden
| | - Helena Johansson
- Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Osteoporosis Centre, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
- Centre for Metabolic Bone Diseases, University of Sheffield, Sheffield, UK
| | - John A Kanis
- Centre for Metabolic Bone Diseases, University of Sheffield, Sheffield, UK
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Ghio C, Gravier-Dumonceau R, Lafforgue P, Giorgi R, Pham T. Identifying a predictive level of serum C-terminal telopeptide associated with a low risk of medication-related osteonecrosis of the jaw secondary to oral surgery: A systematic review and meta-analysis. PLoS One 2025; 20:e0318260. [PMID: 40323917 PMCID: PMC12052178 DOI: 10.1371/journal.pone.0318260] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2024] [Accepted: 01/14/2025] [Indexed: 05/07/2025] Open
Abstract
OBJECTIVE Our aim was to determine serum C-terminal telopeptide of type I collagen (sCTX) thresholds for predicting the minimal risk of medication-related osteonecrosis of the jaw (MRONJ) in patients undergoing anti-resorptive therapy prior to oral surgery. METHODS A systematic literature search was conducted in MEDLINE, EMBase, and the Cochrane Library up to September 2023 for case-control, prospective and retrospective studies that assessed sCTX levels in patients exposed to anti-resorptive drugs who underwent oral surgery. We extracted data using a predetermined form. We performed an original percentile meta-analysis method, following PRISMA-DTA guidelines and descriptive analysis to identify the threshold associated with the lowest risk while assessing the overall result of the 95th, 97.5th and 99th percentiles with a random-effect model with weighting by DerSimonian and Laird (RStudio software [v. 4.2.0]). RESULTS Seven studies involving 1281 patients were included. Most patients (96%) were treated for osteoporosis, predominantly with oral bisphosphonates (94.5%). Individual data were available for 58 patients. In the entire population of patients who experienced MRONJ after oral surgery (n = 113), the 95th, 97.5th and 99th percentiles of sCTX were 338.0 pg/mL [95%CI: 190,3; 485,7], 401.9 pg/mL [95%CI: 191,3; 612,6], and 458.0 pg/mL [95%CI: 190,4; 725,6], respectively. Among those treated with oral bisphosphonates for osteoporosis (n = 38), the sCTX 95th, 97.5th and 99th percentiles were 185.3 pg/mL [95%CI: 131,3; 239,3] 187.4 pg/mL [95%CI: 133,9; 240,8] and 188.6 pg/mL [95%CI: 135,4; 241,9], respectively. The determination of these same percentiles with individual data analysis yielded similar results, i.e., 202.0, 257.0 and 260.0 pg/mL. CONCLUSION This pioneering meta-analysis assesses the risk of MRONJ by analyzing sCTX levels in patients undergoing oral surgery while exposed to antiresorptive drugs. Among patients receiving oral bisphosphonate therapy for osteoporosis, a sCTX threshold of 260 pg/mL is linked to an extremely low risk of MRONJ occurrence, surpassing the 99th percentile. Conversely, for patients undergoing treatment for cancer-related conditions, sCTX levels do not reliably serve as a biomarker for identifying this risk.
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Affiliation(s)
- Camille Ghio
- Department of Rheumatology, Aix Marseille Univ, APHM, Hôpital Sainte-Marguerite, Marseille, France
| | - Robinson Gravier-Dumonceau
- Aix Marseille Univ, APHM, INSERM, IRD, SESSTIM, Sciences Economiques & Sociales de la Santé & Traitement de l’Information Médicale, ISSPAM, Hop Timone, BioSTIC, Biostatistique et Technologies de l’Information et de la Communication, Marseille, France
| | - Pierre Lafforgue
- Department of Rheumatology, Aix Marseille Univ, APHM, Hôpital Sainte-Marguerite, Marseille, France
| | - Roch Giorgi
- Aix Marseille Univ, APHM, INSERM, IRD, SESSTIM, Sciences Economiques & Sociales de la Santé & Traitement de l’Information Médicale, ISSPAM, Hop Timone, BioSTIC, Biostatistique et Technologies de l’Information et de la Communication, Marseille, France
| | - Thao Pham
- Department of Rheumatology, Aix Marseille Univ, APHM, Hôpital Sainte-Marguerite, Marseille, France
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Payer J, Jackuliak P, Vaňuga P, Killinger Z, Dubecká S, Kužma M. National guidelines for diagnosis and treatment of osteoporosis in Slovakia. Arch Osteoporos 2025; 20:56. [PMID: 40319419 PMCID: PMC12050228 DOI: 10.1007/s11657-025-01538-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2025] [Accepted: 04/02/2025] [Indexed: 05/07/2025]
Abstract
BACKGROUND Osteoporosis is a chronic, systemic skeletal disease characterized by decreased bone mass and microarchitectural deterioration, leading to increased fracture risk. In Slovakia, its prevalence is estimated at 6%, with substantial health, social, and economic burdens. OBJECTIVE The Slovak national guideline provides an overview for the diagnosis, prevention, and treatment of osteoporosis in Slovakia, reflecting recent scientific advances and recommendations from international bodies. METHODS The guidelines were developed by a multidisciplinary expert panel and officially adopted by the Ministry of Health of the Slovak Republic. They are based on current evidence and international standards, including FRAX, IOF, ISCD, and ESCEO recommendations. RESULTS Diagnosis involves clinical risk assessment, biochemical testing, and imaging-primarily DXA and trabecular bone score. FRAX with or without BMD enhances risk stratification. Osteoporosis is categorized as primary or secondary. Prevention strategies include lifestyle modification, calcium and vitamin D supplementation, and fall risk reduction. Pharmacologic treatment includes antiresorptive agents (bisphosphonates, denosumab, SERMs), osteoanabolic (teriparatide, romosozumab), and hormone therapy when indicated. Sequential treatment strategies are emphasized, particularly in high-risk individuals. Treatment monitoring includes bone turnover markers and periodic DXA. CONCLUSIONS: The Slovak guidelines provide a comprehensive and pragmatic approach for the management of osteoporosis across all stages, emphasizing early diagnosis, personalized treatment, and long-term fracture prevention. They align with European and global best practices and support clinical decision-making across specialties.
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Affiliation(s)
- Juraj Payer
- 5th Department of Internal Medicine, Faculty of Medicine, Comenius University, University Hospital Bratislava, Ružinovská 6, 82101, Bratislava, Slovakia
- Slovak Society for Osteoporosis and Metabolic Bone Disorders, Bratislava, Slovakia
| | - Peter Jackuliak
- 5th Department of Internal Medicine, Faculty of Medicine, Comenius University, University Hospital Bratislava, Ružinovská 6, 82101, Bratislava, Slovakia
- Slovak Society for Osteoporosis and Metabolic Bone Disorders, Bratislava, Slovakia
| | - Peter Vaňuga
- 5th Department of Internal Medicine, Faculty of Medicine, Comenius University, University Hospital Bratislava, Ružinovská 6, 82101, Bratislava, Slovakia
- Slovak Society for Osteoporosis and Metabolic Bone Disorders, Bratislava, Slovakia
- National Institute of Endocrinology and Diabetology, Lubochna, Slovakia
| | - Zdenko Killinger
- 5th Department of Internal Medicine, Faculty of Medicine, Comenius University, University Hospital Bratislava, Ružinovská 6, 82101, Bratislava, Slovakia
- Slovak Society for Osteoporosis and Metabolic Bone Disorders, Bratislava, Slovakia
| | - Soňa Dubecká
- 5th Department of Internal Medicine, Faculty of Medicine, Comenius University, University Hospital Bratislava, Ružinovská 6, 82101, Bratislava, Slovakia
- Slovak Society for Osteoporosis and Metabolic Bone Disorders, Bratislava, Slovakia
| | - Martin Kužma
- 5th Department of Internal Medicine, Faculty of Medicine, Comenius University, University Hospital Bratislava, Ružinovská 6, 82101, Bratislava, Slovakia.
- Slovak Society for Osteoporosis and Metabolic Bone Disorders, Bratislava, Slovakia.
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20
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Toscano-Angulo JJ, Mora-Macías J, Blázquez-Carmona P, Morgaz J, Navarrete-Calvo R, Domínguez J, Reina-Romo E. Risk of fragility fracture is aggravated during bone regeneration processes in osteoporotic sheep. PLoS One 2025; 20:e0319910. [PMID: 40315244 PMCID: PMC12047778 DOI: 10.1371/journal.pone.0319910] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2024] [Accepted: 02/10/2025] [Indexed: 05/04/2025] Open
Abstract
INTRODUCTION Bone regeneration processes are associated with a systemic skeletal change in bone quality, increasing the risk of fragility fractures. This condition may be aggravated in osteoporotic patients due to their limited osteogenic capacity. This work evaluates the impairment of the bone quality in osteoporotic sheep during a bone regeneration process. It provides a deeper understanding about the complex multiscale dynamics of bone mineral density, microstructure and chemical composition across different bone tissues, locations and time points. MATERIALS AND METHODS Osteoporosis was induced in fifteen Merino sheep. A critical-size defect was then created in the sheep's right hind metatarsus and subsequently regenerated using distraction osteogenesis. The animals were randomly sacrificed during bone regeneration, either on days 40 or 100 after surgery. Computed tomography, micro-computed tomography and chemical composition analyses were conducted on different bone tissues (cortical, trabecular and woven) at several skeletal locations (the operated metatarsus, the contralateral one and the iliac crest) to assess the individual bone quality changes relative to the non-osteoporotic time point. RESULTS After osteoporosis induction, the trabecular tissue experienced a 6.4% reduction in the bone mineral density, while no significant changes were reported in cortical tissue quality. During bone regeneration, the operated bone increased significantly the woven ossification whilst the cortical mineral density decreased by 18.7%. Simultaneously, an early deterioration in the microstructure and chemical composition of the trabecular bone was observed in the iliac crest, persisting over time in non-operated trabecular regions. CONCLUSIONS Osteoporosis causes uneven degradation to trabecular tissue quality across different bone locations. Furthermore, the bone regeneration process via bone transport in osteoporotic subjects leads to a systemic skeletal disorder that further impairs the bone quality, surpassing the damage caused by osteoporosis alone. This impairment appears to be intensified by the pre-existing osteoporotic condition.
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Affiliation(s)
- Juan J. Toscano-Angulo
- Department of Mechanical and Manufacturing Engineering, Escuela Técnica Superior de Ingeniería, Universidad de Sevilla, Sevilla, Spain
| | - Juan Mora-Macías
- Department of Mining, Mechanical, Energy and Building Engineering, Escuela Técnica Superior de Ingeniería, Universidad de Huelva, Huelva, Spain
| | - Pablo Blázquez-Carmona
- Department of Mechanical Engineering and Industrial Design, Escuela Superior de Ingeniería, Universidad de Cádiz, Puerto Real, Spain
| | - Juan Morgaz
- Department of Animal Medicine and Surgery, Facultad de Veterinaria, Universidad de Córdoba, Córdoba, Spain
| | - Rocío Navarrete-Calvo
- Department of Animal Medicine and Surgery, Facultad de Veterinaria, Universidad de Córdoba, Córdoba, Spain
| | - Jaime Domínguez
- Department of Mechanical and Manufacturing Engineering, Escuela Técnica Superior de Ingeniería, Universidad de Sevilla, Sevilla, Spain
| | - Esther Reina-Romo
- Department of Mechanical and Manufacturing Engineering, Escuela Técnica Superior de Ingeniería, Universidad de Sevilla, Sevilla, Spain
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Shashidhara A, Tahir SH, Syed ZA, Lee J, Tahir H. An update on the pharmacotherapy of osteoporosis. Expert Opin Pharmacother 2025; 26:821-833. [PMID: 40178951 DOI: 10.1080/14656566.2025.2489122] [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: 02/19/2025] [Revised: 03/27/2025] [Accepted: 04/01/2025] [Indexed: 04/05/2025]
Abstract
INTRODUCTION Osteoporosis is a chronic metabolic bone disease characterized by progressive bone loss and structural deterioration, increasing fracture risk and morbidity. As the global population ages, its incidence is rising, underscoring the urgent need for more effective prevention and treatment strategies. AREAS COVERED This review synthesizes the latest evidence and guidelines from leading international societies, establishing a contemporary framework for osteoporosis pharmacotherapy. It emphasizes best practices and explores future directions in treatment optimization and fracture prevention. EXPERT OPINION To optimize outcomes, enhancing early detection, refining treatment strategies, and prioritizing patient-centered care are essential. Improving diagnosis through increased use of bone mineral density (BMD) assessments and identifying secondary causes are critical steps to addressing underdiagnosis, particularly in men. Pharmacotherapies play a vital role in management; while bisphosphonates serve as a cost-effective first-line treatment, denosumab and anabolic agents like Teriparatide and romosozumab are essential alternatives for high-risk patients. Future directions in osteoporosis management emphasize advancing treatment strategies through novel drug targets and innovative delivery systems, alongside personalized medicine approaches considering individual genetic and comorbidity profiles. Enhanced adherence strategies and further research into combination therapies and monitoring tools are crucial for improving prevention and treatment outcomes, ultimately reducing the fragility fracture burden worldwide.
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Affiliation(s)
| | | | | | - Jeffrey Lee
- Department of Rheumatology, Royal Free London NHS Foundation Trust, London, UK
- Division of Medicine, University College London, London, UK
| | - Hasan Tahir
- Department of Rheumatology, Royal Free London NHS Foundation Trust, London, UK
- Division of Medicine, University College London, London, UK
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22
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Li X, Deng W, Tang K, Zhang S, Liang Z, Liu W, Li Y, Zhang Z, Zhao W, Zou J. Sophoraflavanone G Inhibits RANKL-Induced Osteoclastogenesis via MAPK/NF-κB Signaling Pathway. Mol Biotechnol 2025; 67:2085-2097. [PMID: 38780825 DOI: 10.1007/s12033-024-01185-8] [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: 01/12/2024] [Accepted: 04/19/2024] [Indexed: 05/25/2024]
Abstract
Osteoporosis is a common chronic bone metabolism disorder characterized by decreased bone mass and reduced bone density in the bone tissue. Osteoporosis can lead to increased fragility of the skeleton, making it prone to brittle fractures. Osteoclasts are macrophage-like cells derived from hematopoietic stem cells, and their excessive activity in bone resorption leads to lower bone formation than absorption during bone remodeling, which is one of the important factors inducing osteoporosis. Therefore, how to inhibit osteoclast formation and reducing bone loss is an important direction for treating osteoporosis. Sophoraflavanone G, derived from Sophora flavescens Alt and Rhizoma Drynariae, is a flavonoid compound with various biological activities. However, there have been few studies on osteoporosis and osteoclasts so far. Therefore, we hypothesize that genistein G can inhibit osteoclast differentiation, alleviate bone loss phenomenon, and conduct in vitro and in vivo experiments for research and verification purposes.
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Affiliation(s)
- Xinchun Li
- Guangzhou University of Chinese Medicine, Guangzhou City, 510405, Guangdong Province, China
- Department of Orthopaedic, Hainan Traditional Chinese Medicine Hospital, Hainan City, China
- Department of Orthopaedic, Affiliated Hainan Traditional Chinese Medicine Hospital, Hainan City, 570203, Hainan Province, China
- Department of Orthopaedic, Affiliated Hainan Traditional Chinese Medicine, Hainan City, 570203, Hainan Province, China
| | - Wei Deng
- Guangzhou University of Chinese Medicine, Guangzhou City, 510405, Guangdong Province, China
- The Laboratory of Orthopaedics and Traumatology of Lingnan Medical Research Center, Guangzhou University of Chinese Medicine, Guangzhou City, 510405, Guangdong Province, China
- Orthopedics Department, The Affiliated TCM Hospital of Guangzhou Medical University, Guangzhou City, 510405, Guangdong Province, China
| | - Kai Tang
- Guangzhou University of Chinese Medicine, Guangzhou City, 510405, Guangdong Province, China
- The Laboratory of Orthopaedics and Traumatology of Lingnan Medical Research Center, Guangzhou University of Chinese Medicine, Guangzhou City, 510405, Guangdong Province, China
- Orthopedics Department, The Affiliated TCM Hospital of Guangzhou Medical University, Guangzhou City, 510405, Guangdong Province, China
| | - Shiyin Zhang
- Guangzhou University of Chinese Medicine, Guangzhou City, 510405, Guangdong Province, China
- The Laboratory of Orthopaedics and Traumatology of Lingnan Medical Research Center, Guangzhou University of Chinese Medicine, Guangzhou City, 510405, Guangdong Province, China
| | - Zixuan Liang
- Guangzhou University of Chinese Medicine, Guangzhou City, 510405, Guangdong Province, China
- The Laboratory of Orthopaedics and Traumatology of Lingnan Medical Research Center, Guangzhou University of Chinese Medicine, Guangzhou City, 510405, Guangdong Province, China
| | - Weiwen Liu
- Guangzhou University of Chinese Medicine, Guangzhou City, 510405, Guangdong Province, China
- The Laboratory of Orthopaedics and Traumatology of Lingnan Medical Research Center, Guangzhou University of Chinese Medicine, Guangzhou City, 510405, Guangdong Province, China
| | - Yongyu Li
- Guangzhou University of Chinese Medicine, Guangzhou City, 510405, Guangdong Province, China
- The Laboratory of Orthopaedics and Traumatology of Lingnan Medical Research Center, Guangzhou University of Chinese Medicine, Guangzhou City, 510405, Guangdong Province, China
| | - Zhida Zhang
- Orthopedics Department, The Affiliated Traditional Chinese Medicine Hospital, Guangzhou Medical University, Guangzhou City, 510405, Guangdong Province, China.
| | - Wenhua Zhao
- Orthopedics Department, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou City, 510260, Guangdong Province, China.
| | - Jian Zou
- Orthopedic Spine Department, Dongguan Hospital of Traditional Chinese Medicine, Dongguan City, 523005, Guangdong Province, China.
- Guangzhou University of Chinese Medicine, Guangzhou City, 510405, Guangdong Province, China.
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23
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Dong X, Liu H, Yuan D, Gulati K, Liu Y. Re-engineering bone: pathogenesis, diagnosis and emerging therapies for osteoporosis. J Mater Chem B 2025; 13:4938-4963. [PMID: 40192254 DOI: 10.1039/d4tb02628d] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/02/2025]
Abstract
Osteoporosis, a multifaceted metabolic bone disease, is becoming increasingly prevalent and poses a significant burden on global healthcare systems. Given the limitations of traditional treatments such as pharmacotherapy, tissue engineering has emerged as a promising alternative for osteoporosis management. This review begins by exploring the pathogenesis of osteoporosis, with a focus on the abnormal metabolic, cellular, and molecular signalling microenvironments that drive the disease. We also examine commonly used clinical diagnostic techniques, discussing their strengths and limitations. Notably, this review evaluates various advanced tissue engineering strategies for osteoporosis treatment. Delivery systems, including injectable hydrogels and nanomaterials, are detailed alongside bone tissue engineering materials such as bioactive ceramics, bone cements, and polymers. Additionally, biologically active substances, including exosomes and cytokines, and emerging therapies that leverage small-molecule drugs are explored. Through a comprehensive analysis of the advantages and limitations of current biomaterials and therapeutic approaches, this review provides insights into future directions for tissue engineering-based solutions. By synthesizing current advancements, it aims to inspire innovative perspectives for the clinical management of osteoporosis.
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Affiliation(s)
- Xinyi Dong
- Central Laboratory, Peking University School and Hospital of Stomatology, Beijing 100081, China.
- National Center for Stomatology & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices Beijing Key Laboratory of Digital Stomatology & Translational Research Center for Oro-craniofacial Stem Cells and Systemic Health, Beijing 100081, China
| | - Hao Liu
- Central Laboratory, Peking University School and Hospital of Stomatology, Beijing 100081, China.
- National Center for Stomatology & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices Beijing Key Laboratory of Digital Stomatology & Translational Research Center for Oro-craniofacial Stem Cells and Systemic Health, Beijing 100081, China
| | - Dian Yuan
- Hubei University of Science and Technology, School of Dentistry and Optometry, Xianning 430030, China
| | - Karan Gulati
- School of Dentistry, The University of Queensland, Herston, QLD, 4006, Australia.
- Centre for Orofacial Regeneration, Reconstruction and Rehabilitation (COR3), Herston, QLD 4006, Australia
| | - Yan Liu
- Central Laboratory, Peking University School and Hospital of Stomatology, Beijing 100081, China.
- Centre for Orofacial Regeneration, Reconstruction and Rehabilitation (COR3), Herston, QLD 4006, Australia
- Department of Orthodontics, Peking University School and Hospital of Stomatology, Beijing 100081, China
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24
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Mahapatra B, Pal B. From healthy to osteoporotic: Exploring how bone quality alters implant performance in Pauwels type III fracture. Proc Inst Mech Eng H 2025; 239:436-447. [PMID: 40257380 DOI: 10.1177/09544119251333671] [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] [Indexed: 04/22/2025]
Abstract
Osteoporosis compromises bone strength, making bone more susceptible to fractures. Decreased bone density heightens susceptibility to femoral neck fractures. The study investigated the impact of bone density on implant performance across three categories of bone quality: healthy, osteopenic, and osteoporotic. The effectiveness of three commonly used implant types (Femoral Neck System, Dynamic Condylar Screw, and Dynamic Hip Screw, where later two equipped with an anti-rotational screw) was evaluated through finite element analysis for treating Pauwels type III fracture. The bone geometry and material properties were based on a subject-specific CT data. The density and Young's modulus of bone elements were adjusted to simulate osteopenic and osteoporotic bone. FE models were developed and the peak loading values for normal walking and stair climbing conditions were considered. Stability and performance of the implant were assessed using bone strain, implant stress, deformation and rotation of the femoral head, micromotion at the interfaces, strain shielding, and risk of implant cut-out. Except for DCS with AR-screw and FNS implants under stair climbing conditions in weaker bone qualities, the implant stress remained within the yield limit of Ti-alloy. The comprehensive assessment identified DHS2 as the preferred implant option for treating such fractures, even in poor bone quality. The risk of cut-out risk was up to 3.9% higher in DCS2 and 6.3% higher in FNS implanted models than in DHS2. The effect of change in bone quality was comparatively less in DHS2 implants than the other two types.
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Affiliation(s)
- Biswajit Mahapatra
- Department of Mechanical Engineering, Indian Institute of Engineering Science and Technology, Howrah, West Bengal, India
| | - Bidyut Pal
- Department of Mechanical Engineering, Indian Institute of Engineering Science and Technology, Howrah, West Bengal, India
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25
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Wei H, Jin Z, Zhou L, Tang G, Chai S, Che X, Tan Y, Zeng W. Association between RBC folate and lumbar bone mineral density in postmenopausal women, a cross-sectional study from NHANES 2009-2018. Front Endocrinol (Lausanne) 2025; 16:1559043. [PMID: 40357211 PMCID: PMC12066272 DOI: 10.3389/fendo.2025.1559043] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/21/2025] [Accepted: 04/03/2025] [Indexed: 05/15/2025] Open
Abstract
Background Postmenopausal women are at an increased risk of bone density reduction, with multiple factors implicated, including folate, a B vitamin whose impact on bone health is gaining attention. The purpose of this research was to examine the association between red blood cell (RBC) folate levels and lumbar bone mineral density (BMD) in postmenopausal women. Methods We performed a cross-sectional study to investigate the association between postmenopausal women's lumbar BMD and RBC folate levels, using the data from the 2009-2018 National Health and Nutrition Examination Survey (NHANES). Participants were categorized into quartiles based on RBC folate levels (Q1-Q4). Univariate and multivariate regression models assessed the association between RBC folate levels and lumbar BMD, with threshold effect analysis performed. Results A total of 1315 postmenopausal women were included. RBC folate levels were positively associated with lumbar BMD. The trend analysis across the quartiles of RBC folate indicated a statistically significant trend in all models (P for trend: Model 1 = 0.020; Model 2 = 0.015; Model 3 = 0.037), suggesting that higher RBC folate levels are associated with increased lumbar BMD. In the unadjusted model 1, a 10 nmol/L increase in RBC folate was associated with a 0.0002 g/cm² increase in lumbar BMD (P=0.002509). The correlation was still significant (P=0.0006) even after age and race were taken into account (model 2). Further adjustment for multiple variables (model 3) showed a 0.0002 g/cm² increase in lumbar BMD per 10 nmol/L increase in RBC folate (P=0.0212). Threshold effect analysis revealed a breakpoint at 92.4 nmol/dL, suggesting a nonlinear relationship between RBC folate levels and lumbar BMD. Conclusions Postmenopausal women's RBC folate levels had a positive association with their lumbar BMD. Maintaining appropriate RBC folate levels may help preserve bone density and offer a fresh approach to avoiding osteoporosis in postmenopausal women.
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Affiliation(s)
- Hua Wei
- Department of Orthopedics, Guilin Municipal Hospital of Traditional Chinese Medicine, Guilin, Guangxi, China
| | - Ziqi Jin
- Department of Orthopedics, Guilin Municipal Hospital of Traditional Chinese Medicine, Guilin, Guangxi, China
- Graduate College, Guangxi University of Chinese Medicine, Nanning, Guangxi, China
| | - Liangji Zhou
- Department of Orthopedics, Guilin Municipal Hospital of Traditional Chinese Medicine, Guilin, Guangxi, China
- Graduate College, Guangxi University of Chinese Medicine, Nanning, Guangxi, China
| | - Gangjian Tang
- Department of Orthopedics, Guilin Municipal Hospital of Traditional Chinese Medicine, Guilin, Guangxi, China
| | - Sheng Chai
- Department of Orthopedics, Guilin Municipal Hospital of Traditional Chinese Medicine, Guilin, Guangxi, China
| | - Xiaoqiao Che
- Department of Orthopedics, Guilin Municipal Hospital of Traditional Chinese Medicine, Guilin, Guangxi, China
| | - Yongxing Tan
- Department of Orthopedics, Guilin Municipal Hospital of Traditional Chinese Medicine, Guilin, Guangxi, China
| | - Weiqing Zeng
- Department of Orthopedics, Guilin Municipal Hospital of Traditional Chinese Medicine, Guilin, Guangxi, China
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26
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Wong RMY, Wong PY, Chau WW, Liu C, Zhang N, Cheung WH. Very high prevalence of osteosarcopenia in hip fracture patients: risk and protective factors. J Orthop Surg Res 2025; 20:423. [PMID: 40296076 PMCID: PMC12036194 DOI: 10.1186/s13018-025-05828-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/03/2025] [Accepted: 04/17/2025] [Indexed: 04/30/2025] Open
Abstract
BACKGROUND Hip fractures are one of the most serious forms of osteoporotic fractures. Osteosarcopenia is a growing geriatric giant with increased risk of falls, fractures, disability and mortality. The objective of this cross-sectional study was to determine the prevalence and risk factors of osteosarcopenia amongst hip fracture patients. METHODS All patients received a dual energy x-ray absorptiometry (DXA) scan for diagnosis of osteopenia and osteoporosis. For sarcopenia assessment, patients received a bioimpedance analysis (BIA) measurement, handgrip strength and 5-time chair stand test. Osteosarcopenia was defined with the presence of osteopenia/osteoporosis and sarcopenia. Risk factors for osteosarcopenia were analysed using logistic regression. RESULTS A total of 342 hip fracture patients (n = 342) were recruited. Sarcopenia was present in 286 hip fracture patients (83.6%). 335 hip fracture patients (97.95%) had osteopenia/osteoporosis. Osteosarcopenia was present in 281 hip fracture patients (82.2%). For osteosarcopenia, patients with body mass index (BMI) < 23 kg/m2 were 4.33 (2.35 to 7.95; p < 0.001) times more likely to have osteosarcopenia regardless of age and gender. Males were 3.24 (1.38 to 7.58; p = 0.007) more likely to have osteosarcopenia regardless of age and BMI group. CONCLUSIONS Our study had shown a very high prevalence of osteosarcopenia amongst hip fracture patients, especially in male patients, and identified associated risk and protective factors. Given the potential clinical implications, we would recommend that in addition to bone mineral density assessment, routine sarcopenia assessment should also be incorporated into Fracture Liaison Services. Further research should be conducted on optimal body weight and BMI, and as to why male patients have more likelihood of sarcopenia.
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Affiliation(s)
- Ronald Man Yeung Wong
- Department of Orthopaedics & Traumatology, The Chinese University of Hong Kong, Hong Kong SAR, China.
| | - Pui Yan Wong
- Department of Orthopaedics & Traumatology, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Wai Wang Chau
- Department of Orthopaedics & Traumatology, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Chaoran Liu
- Department of Orthopaedics & Traumatology, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Ning Zhang
- Department of Orthopaedics & Traumatology, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Wing Hoi Cheung
- Department of Orthopaedics & Traumatology, The Chinese University of Hong Kong, Hong Kong SAR, China
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Hunegnaw MT, Mesinovic J, Jansons P, George ES, De Ross B, Kiss N, Ebeling PR, Daly RM, Gvozdenko E, Scott D. Feasibility and effectiveness of a digital voice assistant for improving anti-osteoporosis medication adherence, and osteoporosis knowledge and attitudes, in postmenopausal women with osteoporosis: A 12-month randomised controlled trial. Arch Osteoporos 2025; 20:43. [PMID: 40202535 PMCID: PMC11982083 DOI: 10.1007/s11657-025-01529-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/04/2024] [Accepted: 03/15/2025] [Indexed: 04/10/2025]
Abstract
Digital voice assistants (DVAs) are feasible for delivering a digital health intervention designed to improve osteoporosis self-management in postmenopausal women with osteoporosis. However, the DVA intervention did not improve anti-osteoporosis drug adherence, nor did it enhance osteoporosis knowledge or attitudes in this population. PURPOSE To determine feasibility and effectiveness of a digital voice assistant (DVA) intervention for improving anti-osteoporosis medication adherence, and osteoporosis knowledge and attitudes, in postmenopausal women with osteoporosis. METHODS This 12-month single-blinded, randomised controlled trial included 50 postmenopausal women with osteoporosis randomised to DVA (N = 25) or control (N = 25) for 6 months, followed by a 6-month follow-up period. DVA participants received an Amazon Alexa device that delivered osteoporosis education videos, medication reminders and interactive quizzes. Control participants received emails with links to osteoporosis information. Anti-osteoporosis medication possession ratio (MPR; acceptable adherence defined as ≥ 0.8) was determined using Pharmaceutical Benefits Schedule data. Osteoporosis knowledge was measured using the Osteoporosis Knowledge Assessment Tool (OKAT) and medication attitudes were measured using the Adherence Evaluation of Osteoporosis Treatment (ADEOS-12) questionnaire. RESULTS The mean ± SD age of participants was 64.3 ± 6.1 years and 6-month DVA intervention adherence (number of DVA sessions accessed) was 79.5% (95%CI: 73.9, 84.9). The proportion of participants with acceptable 12-month MPRs was similar between groups (control: 86.4% [95%CI: 77.0, 93.6]; DVA: 95.0% [95%CI: 88.4, 100.0], P = 0.34). Mean OKAT scores improved in both groups after both 6- and 12 months, but there were no significance between groups. Changes in mean ADEOS-12 scores did not differ between baseline and 6 months in DVA compared to control (0.61 [95%CI: - 0.80, 2.03]) but worsened post-intervention from 6 to 12 months (net difference: - 1.42 [95%CI: - 2.80, - 0.06]). CONCLUSIONS This DVA-delivered intervention achieved good adherence but did not improve medication adherence, osteoporosis knowledge, or attitudes compared with control. Future studies should target populations with poor adherence to anti-osteoporosis medication.
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Affiliation(s)
- Melkamu Tamir Hunegnaw
- Institute for Physical Activity and Nutrition, Deakin University, Geelong, Australia.
- University of Gondar College of Medicine and Health Sciences, Institute of Public Health, Gondar, Ethiopia.
| | - Jakub Mesinovic
- Institute for Physical Activity and Nutrition, Deakin University, Geelong, Australia
- Department of Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, Australia
| | - Paul Jansons
- Institute for Physical Activity and Nutrition, Deakin University, Geelong, Australia
- Department of Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, Australia
| | - Elena S George
- Institute for Physical Activity and Nutrition, Deakin University, Geelong, Australia
| | - Belinda De Ross
- Institute for Physical Activity and Nutrition, Deakin University, Geelong, Australia
| | - Nicole Kiss
- Institute for Physical Activity and Nutrition, Deakin University, Geelong, Australia
| | - Peter R Ebeling
- Department of Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, Australia
| | - Robin M Daly
- Institute for Physical Activity and Nutrition, Deakin University, Geelong, Australia
| | | | - David Scott
- Institute for Physical Activity and Nutrition, Deakin University, Geelong, Australia
- Department of Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, Australia
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Bucak ÖF, Cinar C. The Role of ChatGPT in osteoporosis management: a comparative analysis with clinical expertise. Arch Osteoporos 2025; 20:51. [PMID: 40205011 DOI: 10.1007/s11657-025-01533-4] [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: 12/26/2024] [Accepted: 03/13/2025] [Indexed: 04/11/2025]
Abstract
This study evaluates the role of ChatGPT in osteoporosis management, demonstrating 91% diagnostic accuracy and significantly faster response times compared to clinicians. The findings highlight the potential for artificial intelligence (AI) to revolutionize clinical decision-making while emphasizing the critical need for professional oversight to ensure patient safety and comprehensive care. OBJECTIVE Osteoporosis is a progressive skeletal disease that is characterized by increased bone fragility and an increased risk of fracture. Early diagnosis and effective treatment can significantly reduce healthcare costs; however, limited access to clinical expertise represents a significant challenge to patient care. This study evaluates the diagnostic and treatment recommendations provided by natural language processing (NLP)-based AI models for osteoporosis management and compares them with those of healthcare professionals. METHODS A multicenter, cross-sectional study was conducted with the creation of 100 real scenarios from 206 patients with a diagnosis of osteoporosis. The data pertaining to bone mineral density (BMD) and the clinical parameters were subjected to analysis using ChatGPT-4.0. Thereafter, the recommendations proffered by this software were compared to those of five independent physiatrists. A statistical validation of the model's accuracy was conducted through the use of categorical distribution analysis. RESULTS ChatGPT exhibited a high degree of diagnostic accuracy, with 91% of responses being entirely accurate. It provided recommendations for both pharmacological and non-pharmacological interventions that were consistent with current clinical guidelines. Nevertheless, 8% of the responses were reported as incomplete. Furthermore, ChatGPT was able to produce diagnoses and treatment recommendations at a significantly faster rate than clinicians, while the mean answer time is 5.4 ± 2.45 min in clinicians and 2.3 ± 0.76 min in ChatGPT (p < 0.001). CONCLUSION These findings highlight the potential of AI tools like ChatGPT to improve efficiency in clinical decision-making while underscoring the necessity of collaboration with healthcare professionals to guarantee comprehensive patient care.
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Affiliation(s)
- Ömer Faruk Bucak
- Başakşehir Çam and Sakura City Hospital, Physical Medicine and Rehabilitation, University of Health Sciences, İstanbul, Turkey.
| | - Cigdem Cinar
- Department of Interventional Physiatry, Biruni University, Istanbul, Turkey
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Deng B, Xu T, Deng Z, Jiang Y, Li L, Liang W, Zhang Y, Wang H, Xu Y, Chen G. Efficacy of acupuncture-related therapy for postmenopausal osteoporosis: a systematic review and network meta-analysis based on randomized controlled trials. Front Med (Lausanne) 2025; 12:1483819. [PMID: 40270507 PMCID: PMC12015985 DOI: 10.3389/fmed.2025.1483819] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2024] [Accepted: 03/18/2025] [Indexed: 04/25/2025] Open
Abstract
Introduction To compare and analyze the clinical effects of acupuncture-related therapies for postmenopausal osteoporosis (PMOP) and propose the optimal scheme, we utilized a network meta-analysis to evaluate the therapeutic effects of various commonly used acupuncture methods for PMOP. Methods Randomized controlled trials of acupuncture-related therapies for PMOP were searched in eight databases (PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, China Science and Technology Journal Database, China Biomedical Literature Database, and Wanfang database) from January 1, 2002 to December 31, 2023. Our primary outcomes included overall clinical effectiveness rate, bone mineral density (BMD), and visual analog scale scores (VAS). The secondary outcome is adverse events. The entire process of literature screening and data analysis was conducted by 2 independent investigators. Results A total of 30 studies with 2,342 participants provided data suitable for analysis. We compared six interventions: manual acupuncture, electroacupuncture, acupoint catgut embedding, moxibustion, acupoint application, and warm acupuncture. The results of the network meta-analysis revealed that, when compared to conventional Western medication (CWM), multiple acupuncture therapies had a greater impact on the overall clinical effectiveness rate. Electroacupuncture combined with CWM demonstrated superior clinical effectiveness and lumbar spine BMD improvement. Moxibustion with CWM ranked highest for femoral neck BMD, while warm acupuncture showed optimal effects on Ward's triangle and trochanter BMD. Acupoint catgut embedding provided the greatest pain reduction. The most prevalent minor adverse effects included hematoma, discomfort, and scorching. Conclusion The results suggest that several acupuncture-related therapies, either alone or in conjunction with CWM, outperform CWM alone and may be regarded as an alternative or supplementary therapy to PMOP, though higher-quality trials are needed.
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Affiliation(s)
- Bing Deng
- Shenzhen Bao’an Traditional Chinese Medicine Hospital, Guangzhou University of Chinese Medicine, Shenzhen, China
- Clinical Medical College of Acupuncture-Moxibustion and Rehabilitation, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Tiantian Xu
- Clinical Medical College of Acupuncture-Moxibustion and Rehabilitation, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Zilan Deng
- Clinical Medical College of Acupuncture-Moxibustion and Rehabilitation, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Yue Jiang
- Clinical Medical College of Acupuncture-Moxibustion and Rehabilitation, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Li Li
- Shenzhen Bao’an Traditional Chinese Medicine Hospital, Guangzhou University of Chinese Medicine, Shenzhen, China
| | - Wankun Liang
- Shenzhen Bao’an Traditional Chinese Medicine Hospital, Guangzhou University of Chinese Medicine, Shenzhen, China
| | - Yuewen Zhang
- Clinical Medical College of Acupuncture-Moxibustion and Rehabilitation, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Hongjin Wang
- Clinical Medical College of Acupuncture-Moxibustion and Rehabilitation, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Yunxiang Xu
- Clinical Medical College of Acupuncture-Moxibustion and Rehabilitation, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Guizhen Chen
- Shenzhen Bao’an Traditional Chinese Medicine Hospital, Guangzhou University of Chinese Medicine, Shenzhen, China
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Tao R, Qiao MQ, Wang B, Fan JP, Gao F, Wang SJ, Guo SY, Xia SL. Laboratory-based Biomarkers for Risk Prediction, Auxiliary Diagnosis and Post-operative Follow-up of Osteoporotic Fractures. Curr Osteoporos Rep 2025; 23:19. [PMID: 40199776 PMCID: PMC11978538 DOI: 10.1007/s11914-025-00914-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 03/26/2025] [Indexed: 04/10/2025]
Abstract
PURPOSE OF REVIEW Osteoporosis (OP) is characterized by degraded bone microstructure, loss of bone mass and increased risk of fragility fractures. Currently, T-score determined by dual-energy X-ray absorptiometry (DEXA) measurements has been regarded as the gold standard for the diagnosis of osteoporosis. However, multiple factors have indicated that the T-score is insufficient to identify individuals with osteoporosis at a potentially high risk of fracture, or accurately detect those who require treatment, or continuously monitor the risk of re-fracture and clinical outcomes after treatment. This review covers publications in a range of ten years and comprehensively summarizes the studies in laboratory-based biomarkers for osteoporotic fractures (OF), aiming to provide physicians and surgeons with an update of clinical research in identification, verification and application of these tools, and to provide useful information for the design of future clinical studies. RECENT FINDINGS It was found that bone formation markers (such as PINP, BGP, ECM1 and SOST), bone resorption markers (such as β-CTX, TRAcP5b, osteocalcin, RANKL, RANKL/OPG ratio, and t-PINP/β-CTX), hormonal biomarkers (such as IGF- 1, PTH, leptin, adiponectin and AMH), indicators of inflammation and oxidative stress (SII, IL- 6, LTL, FlOP_360, FlOP_400, and GGT), microRNAs (such as miR- 21, miR- 320a- 3p, miR- 491 - 5p, miR- 485 - 3p, miR- 19b- 1- 5p, miR- 203a, miR- 31 - 5p, miR- 502 - 3p, miR- 4739, miR- 497, miR- 19b, and miR- 107), other biomarkers (SAF-AGEs and glycine), adipocytokines (irisin and Omentin- 1), senescence biomarkers (RDW), and lncRNAs (MIAT) may be useful biomarkers for clinical practice. Further validation of these biomarkers and a better understanding of the underlying molecular mechanisms may help in the development and application of these biomarkers for risk prediction of OF, differential diagnosis among OP, OF and healthy individuals, as well as post-operative monitoring of re-fracture risk and treatment outcomes.
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Affiliation(s)
- Rui Tao
- Department of Orthopedics, Shanghai University of Medicine & Health Sciences Affiliated Zhoupu Hospital, 1500 Zhoupu Zhouyuan Road, Pudong New Area, Shanghai, 201318, China
- Graduate School, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Pudong New Area, Shanghai, 201203, China
| | - Mei-Qi Qiao
- Department of Orthopedics, Shanghai University of Medicine & Health Sciences Affiliated Zhoupu Hospital, 1500 Zhoupu Zhouyuan Road, Pudong New Area, Shanghai, 201318, China
- Graduate School, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Pudong New Area, Shanghai, 201203, China
| | - Bin Wang
- Department of Orthopedics, Shanghai University of Medicine & Health Sciences Affiliated Zhoupu Hospital, 1500 Zhoupu Zhouyuan Road, Pudong New Area, Shanghai, 201318, China
| | - Jian-Pin Fan
- Department of Orthopedics, Shanghai University of Medicine & Health Sciences Affiliated Zhoupu Hospital, 1500 Zhoupu Zhouyuan Road, Pudong New Area, Shanghai, 201318, China
| | - Feng Gao
- Department of Orthopedics, Shanghai University of Medicine & Health Sciences Affiliated Zhoupu Hospital, 1500 Zhoupu Zhouyuan Road, Pudong New Area, Shanghai, 201318, China
| | - Shao-Jun Wang
- Department of Orthopedics, Shanghai University of Medicine & Health Sciences Affiliated Zhoupu Hospital, 1500 Zhoupu Zhouyuan Road, Pudong New Area, Shanghai, 201318, China
| | - Sheng-Yang Guo
- Department of Orthopedics, Shanghai University of Medicine & Health Sciences Affiliated Zhoupu Hospital, 1500 Zhoupu Zhouyuan Road, Pudong New Area, Shanghai, 201318, China
| | - Sheng-Li Xia
- Department of Orthopedics, Shanghai University of Medicine & Health Sciences Affiliated Zhoupu Hospital, 1500 Zhoupu Zhouyuan Road, Pudong New Area, Shanghai, 201318, China.
- Graduate School, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Pudong New Area, Shanghai, 201203, China.
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Sicras-Mainar A, Sorio-Vilela F, Sacrest-Soy M, Gatell S, Sicras-Navarro A, Villoro-Valdés R, Rebollo-Gómez E, Hernández I. Real-World Osteoporosis Treatment Gap and Costs in Spain: Data from Women with a First Fragility Fracture or Diagnosis of Postmenopausal Osteoporosis. Rheumatol Ther 2025; 12:315-335. [PMID: 39932674 PMCID: PMC11920490 DOI: 10.1007/s40744-024-00743-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2024] [Accepted: 12/23/2024] [Indexed: 03/19/2025] Open
Abstract
INTRODUCTION Postmenopausal osteoporosis (PMO) increases the risk of fragility fractures (FF), leading to disability, higher mortality, and elevated healthcare costs. Despite available treatments, osteoporosis (OP) remains undertreated, especially in women over 50 years at high risk for FF. Real-world data on OP care in Spain are limited. This study aims to assess the OP treatment gap, healthcare resource utilisation (HCRU), and costs among Spanish women following a first FF or PMO diagnosis. METHODS This retrospective study used data from the BIG-PAC® administrative database on women aged ≥ 50 years with a first FF (cohort 1) or newly diagnosed PMO (cohort 2) between 2014 and 2018. Patients were followed for 2 years after the index event. The primary outcome was the proportion of women not prescribed OP medication within 6 months after the index event (treatment gap). Secondary outcomes included fracture incidence, mortality, HCRU, and costs. RESULTS The study included 22,142 women: 3190 in cohort 1 and 18,952 in cohort 2. The OP treatment gap was higher in cohort 1 vs cohort 2 (41.5% vs 23.6%). In cohort 1, 59.2% were diagnosed with PMO after the first FF, with 88% experiencing subsequent fracture(s). OP treatment persistence decreased over time in both cohorts. Fracture rates were lower in women prescribed OP treatment vs those who were not (8.35 vs 13.8 per 1000 patient-years) and in those who showed 24-month-persistence and 12-month adherence to treatment vs those who did not (8.98 and 7.66 vs 10.79 and 10.76). The 2-year mean cost per patient was higher in cohort 1 (€10,601) than in cohort 2 (€1659), with the highest costs incurred for hip (€15,833) and vertebral (€10,593) fractures. CONCLUSION This study highlights a significant treatment gap in Spanish women aged ≥ 50 with a first FF or newly diagnosed PMO. Costs are particularly high for those with a first FF, especially for hip or vertebral fractures. Improving treatment adherence could reduce fracture risk, healthcare costs, and resource utilisation.
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Affiliation(s)
| | | | | | | | | | - Renata Villoro-Valdés
- Health Economics and Outcomes Research, Atrys Health, c/Príncipe de Vergara 132, 28002, Madrid, Spain
| | - Elena Rebollo-Gómez
- Health Economics and Outcomes Research, Atrys Health, c/Príncipe de Vergara 132, 28002, Madrid, Spain
| | - Ignacio Hernández
- Health Economics and Outcomes Research, Atrys Health, c/Príncipe de Vergara 132, 28002, Madrid, Spain.
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Wolf JVE, Schoene D, Kohl M, Kemmler W, Kiesswetter E. Effects of combined protein and exercise interventions on bone health in middle-aged and older adults - A systematic literature review and meta-analysis of randomized controlled trials. Osteoporos Int 2025; 36:609-625. [PMID: 39915336 PMCID: PMC12064458 DOI: 10.1007/s00198-025-07393-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/16/2024] [Accepted: 01/11/2025] [Indexed: 05/10/2025]
Abstract
PURPOSE Osteoporosis has become a global public health concern making prevention and treatment essential to reduce severe consequences for individuals and health systems. This systematic review with meta-analysis aimed to determine the effects of combined protein and exercise interventions compared to (a) exercise alone and (b) protein alone on bone mineral content (BMC) or density (BMD) in middle-aged and older adults. METHODS We systematically searched Medline, CINAHL, CENTRAL, Web of Science, and SPORTDiscus until 24th January 2023. Pairwise random-effects meta-analyses were performed to calculate weighted mean differences (WMD) with 95% confidence intervals (95% CI). We evaluated risk of bias (Cochrane RoB2) and certainty of evidence (CoE; GRADE). If pooling was not possible, the results were summarized descriptively. RESULTS For the comparison of combined protein supplementation and exercise vs. exercise alone, no meta-analysis for BMD (2 RCTs) was possible. For BMC, little to no intervention effect was found (WMD 0.03 kg; 95% CI - 0.00 to 0.05; 4 RCTs; IG = 97/CG = 98; I2 = 58.4%). In a sensitivity analysis, restricted to combined milk-protein supplementation and exercise, the result remained similar (0.01 kg; 95% CI - 0.01 to 0.03; 4 RCTs; IG = 71/CG = 71; I2 = 0.0%; low CoE). For the comparison of combined protein and exercise interventions vs. protein alone, no RCT on BMC was identified; the results on total or regional BMD (2 RCTs) were inconclusive. CONCLUSION Based on our findings, no robust conclusions can be drawn on whether combining protein and exercise interventions is more beneficial for bone health than one component alone. Sufficiently powered studies with longer duration are required to clarify these questions (CRD42022334026).
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Affiliation(s)
- Julia V E Wolf
- Institute of Radiology, University Hospital Erlangen, Erlangen, Germany
| | - Daniel Schoene
- Institute of Radiology, University Hospital Erlangen, Erlangen, Germany
- Department of Clinical Gerontology, Robert-Bosch-Hospital, Stuttgart, Germany
- Institute of Epidemiology and Medical Biometry, Ulm University, Ulm, Germany
| | - Matthias Kohl
- Department of Medical and Life Sciences, University of Furtwangen, Schwenningen, Germany
| | - Wolfgang Kemmler
- Institute of Radiology, University Hospital Erlangen, Erlangen, Germany
| | - Eva Kiesswetter
- Institute for Biomedicine of Aging, Friedrich-Alexander-Universität Erlangen-Nürnberg, Nuremberg, Germany.
- Institute for Evidence in Medicine, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
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Tedesco C, Bernalte-Martí V, Pucciarelli G, Vellone E, Basilici Zannetti E, Cittadini N, Pennini A, Tarantino U, Alvaro R. Self-care experiences and behaviors in people with osteoporosis: A meta-synthesis. Maturitas 2025; 195:108213. [PMID: 39914137 DOI: 10.1016/j.maturitas.2025.108213] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2024] [Revised: 01/27/2025] [Accepted: 01/30/2025] [Indexed: 03/15/2025]
Abstract
Osteoporosis is a chronic systemic skeletal disease that can benefit from patient-led self-care behaviors. The purpose of this meta-synthesis is to summarize the knowledge about the experiences in self-care behaviors, according to Riegel's middle-range theory of self-care, of patients affected by osteoporosis. A systematic review of the literature and a meta-synthesis of the results were performed to identify qualitative and mixed-method studies through database research conducted on six databases until June 2023 that identified 27 articles. Three dimensions of self-care were recognized within the articles: 'maintenance' was the most reported, mostly associated with therapy adherence; 'monitoring', predominantly related to instrumental test; and, 'management', mainly related to the management of symptoms. A cross-cutting topic that emerges and has been shown to be relevant is that of the relationship with health professionals.
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Affiliation(s)
- Chiara Tedesco
- University of Rome Tor Vergata Department of Biomedicine and Prevention, Italy
| | | | | | - Ercole Vellone
- University of Rome Tor Vergata Department of Biomedicine and Prevention, Italy; Faculty of Nursing and Midwifery, Wroclaw Medical University, Wroclaw, Poland
| | | | - Noemi Cittadini
- University of Rome Tor Vergata Department of Biomedicine and Prevention, Italy
| | - Annalisa Pennini
- University of Rome Tor Vergata Department of Biomedicine and Prevention, Italy
| | | | - Rosaria Alvaro
- University of Rome Tor Vergata Department of Biomedicine and Prevention, Italy
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Kong CH, Steffi C, Cai Y, Wang W. E-jet printed polycaprolactone with strontium-substituted mesoporous bioactive glass nanoparticles for bone tissue engineering. BIOMATERIALS ADVANCES 2025; 169:214173. [PMID: 39754870 DOI: 10.1016/j.bioadv.2024.214173] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/03/2024] [Revised: 12/29/2024] [Accepted: 12/30/2024] [Indexed: 01/06/2025]
Abstract
Osteoporosis, characterized by reduced bone mineral density and increased fracture risk, poses a significant health challenge, particularly for aging populations. Systemic treatments often lead to adverse side effects, emphasizing the need for localized solutions. This study introduces a 3D-printed polycaprolactone (PCL) scaffold embedded with strontium-substituted mesoporous bioactive glass nanoparticles (Sr-MBGNPs) and icariin (ICN) for the targeted regeneration of osteoporotic bone. The scaffold was characterized using scanning electron microscopy (SEM), energy-dispersive spectroscopy (EDS), ion release studies, and cellular assays, which confirmed its dual functionality in both enhancing osteoblast proliferation and differentiation and inhibiting osteoclastogenesis. The optimized Sr-MBGNP concentration ensured sustained ion release, superior hydrophilicity, and bioactivity without compromising scaffold integrity. Additionally, e-jet printing provided high precision and uniform pore sizes conducive to cellular activity. This novel scaffold platform demonstrates a promising localized treatment strategy, reducing systemic side effects while improving fixation stability. The innovative integration of Sr-MBGNPs and ICN highlights its potential to revolutionize osteoporosis therapy by promoting bone regeneration and mitigating bone resorption.
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Affiliation(s)
- Chee Hoe Kong
- Department of Orthopaedic Surgery, National University of Singapore, NUHS Tower Block, Level 11, 1E Kent Ridge Road, Singapore 119228, Singapore.
| | - Chris Steffi
- Institut für Biomechanik, ETH Zürich, GLC H 20.2, Gloriastrasse 37/39, 8092 Zürich, Switzerland
| | - Yanli Cai
- NUS Centre for Additive Manufacturing (AM.NUS), National University of Singapore, Singapore 117597, Singapore
| | - Wilson Wang
- Department of Orthopaedic Surgery, National University of Singapore, NUHS Tower Block, Level 11, 1E Kent Ridge Road, Singapore 119228, Singapore
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Salcuni AS, Brunetti A, Marchese F, Carpentieri M, Baraldo M, Angelini J, Palermo A, Vescini F. Application of Calcaneal Ultrasonography for Long-Term Fracture Risk Assessment in Diabetic Osteopathy. Clin Endocrinol (Oxf) 2025. [PMID: 40166921 DOI: 10.1111/cen.15245] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2024] [Revised: 03/14/2025] [Accepted: 03/21/2025] [Indexed: 04/02/2025]
Abstract
OBJECTIVE Bone densitometry and fracture risk algorithms have proved scarce reliability for fractures risk estimation in patients with diabetic osteopathy. Calcaneal quantitative ultrasound (QUS) is a noninvasive, low-cost technique already acknowledged for fracture risk assessment in patients with primary osteoporosis. Nevertheless, there is limited evidence on the role of QUS in patients with diabetes mellitus (DM). The aim of our study was to evaluate whether calcaneal QUS may effectively estimate long-term risk of fragility fractures in a group of patients with DM. DESIGN We conducted a retrospective study including 300 patients with type 1 (T1DM) or type 2 DM (T2DM) who underwent calcaneal QUS evaluation in 2013. Information about clinical fragility fractures, DM characteristics, and QUS parameters (broadband ultrasound attenuation, BUA; speed of sound, SOS; stiffness index, SI) were collected through electronic medical records. Ten years later, the patients were asked to participate to an interview about clinical fragility fractures occurring within the decade 2013-2023. PATIENTS AND MEASUREMENT At baseline, thirty-nine patients (13%) presented with at least one fragility fracture at any site. Fractured patients showed significantly lower QUS parameters than non-fractured (p < 0.0001), both in T1DM (n = 106) and in T2DM (n = 194). In 2023, 231 patients (132 with T2DM and 99 with T1DM) participated to the follow-up interview; 31 patients (13%) referred the occurrence a new clinical fragility fracture, and 14 patients (6%) a major osteoporotic fractures (MOF). Among QUS parameters, BUA was significantly associated to the occurrence of new MOF over 10-years in T2DM (p < 0.01), but not in T1DM. CONCLUSIONS Calcaneal QUS may represent an effective tool in assessment of fracture risk among patients with T2DM.
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Affiliation(s)
| | | | - Francesca Marchese
- Endocrinology Unit, University Hospital Friuli Centrale ASUFC, Udine, Italy
| | - Maria Carpentieri
- Endocrinology Unit, University Hospital Friuli Centrale ASUFC, Udine, Italy
| | - Massimo Baraldo
- Clinical Pharmacology and Toxicology Institute, University Hospital Friuli Centrale ASUFC, Udine, Italy
- Department of Medicine (DMED), University of Udine (UNIUD), Udine, Italy
| | - Jacopo Angelini
- Clinical Pharmacology and Toxicology Institute, University Hospital Friuli Centrale ASUFC, Udine, Italy
- Department of Medicine (DMED), University of Udine (UNIUD), Udine, Italy
| | - Andrea Palermo
- Unit of Metabolic Bone and Thyroid Diseases, Fondazione Policlinico Universitario Campus Bio-Medico, Rome, Italy
| | - Fabio Vescini
- Endocrinology Unit, University Hospital Friuli Centrale ASUFC, Udine, Italy
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Patiño-Salazar JD, Ovejero D, Gabernet M, Martínez-Gil N, Alcaide-Consuegra E, Mellibovsky L, Nogués X, Grinberg D, Balcells S, Rabionet R, Garcia-Giralt N. Identifying rare variants in genes related to bone phenotypes in a cohort of postmenopausal women. Osteoporos Int 2025; 36:637-644. [PMID: 39915337 PMCID: PMC12064449 DOI: 10.1007/s00198-025-07413-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/20/2024] [Accepted: 01/24/2025] [Indexed: 05/10/2025]
Abstract
Rare genetic variants in genes previously described to be involved in bone monogenic disorders were identified in postmenopausal women split into two groups according to extreme bone mineral density (BMD) values and lumbar spine Z-scores. A pathogenic variant in COL1A2 gene found in a woman with low BMD highlights the overlap between osteogenesis imperfecta and osteoporosis, which may share their genetic etiology. Other variants were not clearly associated with the extreme BMD, suggesting that there is little contribution of rare variants to postmenopausal osteoporosis. PURPOSE We aimed to evaluate whether extreme values of bone mineral density (BMD) in a population-based cohort of postmenopausal women (BARCOS) could be determined by rare genetic variants in genes related to monogenic bone disorders. METHODS A panel of 127 genes related to different skeletal phenotypes was designed. Massive sequencing by targeted capture of these genes was performed in 104 DNA samples from those women of the BARCOS cohort that exhibited the highest (HZ group) and lowest (LZ group) LS Z-scores, ranging from + 0.70 to + 3.80 and from - 2.35 to - 4.26, respectively. 5'UTR, 3'UTR, splice region, missense, nonsense, and short indel variants with MAF < 0.01 were annotated with CADD version 1.6 and considered in the analysis. RESULTS After filtering those variants with CADD > 25 and present only in one of the groups (either LZ or HZ), six variants were detected, most of which (5/6) were in the LZ group in TCIRG1, COL1A2, SEC24D, LRP4, and ANO5 genes, while only one, in the LMNA gene, was in the HZ group. According to the ClinVar database, the COL1A2 variant, causative of a recessive form of osteogenesis imperfecta, is described as pathogenic, while the other variants are considered of uncertain significance (VUS). CONCLUSION The variant identified in COL1A2 in a woman from the LZ group highlights the genetic overlap between monogenic diseases such as osteogenesis imperfecta and complex diseases like osteoporosis. However, the other variants were not clearly associated with the extreme BMD, suggesting that there is little contribution of rare variants to postmenopausal osteoporosis.
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Affiliation(s)
- J D Patiño-Salazar
- Department of Genetics, Microbiology and Statistics, Faculty of Biology, Universitat de Barcelona, CIBERER, IBUB, IRSJD, Barcelona, Spain
| | - D Ovejero
- Musculoskeletal Research Group, Hospital del Mar Research Institute, Centro de Investigación Biomédica en Red en Fragilidad y Envejecimiento Saludable (CIBERFES), ISCIII, Barcelona, Spain
| | - M Gabernet
- Department of Genetics, Microbiology and Statistics, Faculty of Biology, Universitat de Barcelona, CIBERER, IBUB, IRSJD, Barcelona, Spain
| | - N Martínez-Gil
- Department of Genetics, Microbiology and Statistics, Faculty of Biology, Universitat de Barcelona, CIBERER, IBUB, IRSJD, Barcelona, Spain
| | - E Alcaide-Consuegra
- Department of Genetics, Microbiology and Statistics, Faculty of Biology, Universitat de Barcelona, CIBERER, IBUB, IRSJD, Barcelona, Spain
| | - L Mellibovsky
- Musculoskeletal Research Group, Hospital del Mar Research Institute, Centro de Investigación Biomédica en Red en Fragilidad y Envejecimiento Saludable (CIBERFES), ISCIII, Barcelona, Spain
| | - X Nogués
- Musculoskeletal Research Group, Hospital del Mar Research Institute, Centro de Investigación Biomédica en Red en Fragilidad y Envejecimiento Saludable (CIBERFES), ISCIII, Barcelona, Spain
| | - D Grinberg
- Department of Genetics, Microbiology and Statistics, Faculty of Biology, Universitat de Barcelona, CIBERER, IBUB, IRSJD, Barcelona, Spain
| | - S Balcells
- Department of Genetics, Microbiology and Statistics, Faculty of Biology, Universitat de Barcelona, CIBERER, IBUB, IRSJD, Barcelona, Spain.
| | - R Rabionet
- Department of Genetics, Microbiology and Statistics, Faculty of Biology, Universitat de Barcelona, CIBERER, IBUB, IRSJD, Barcelona, Spain
| | - N Garcia-Giralt
- Musculoskeletal Research Group, Hospital del Mar Research Institute, Centro de Investigación Biomédica en Red en Fragilidad y Envejecimiento Saludable (CIBERFES), ISCIII, Barcelona, Spain
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Vieira A, Santos R. Osteoporosis Evaluation by Radiofrequency Echographic Multispectrometry (REMS) in Primary Healthcare. Diagnostics (Basel) 2025; 15:808. [PMID: 40218158 PMCID: PMC11988531 DOI: 10.3390/diagnostics15070808] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2025] [Revised: 03/19/2025] [Accepted: 03/20/2025] [Indexed: 04/14/2025] Open
Abstract
Background/Objectives: Radiofrequency echographic multispectrometry (REMS) technology has emerged as a promising alternative for osteoporosis diagnosis. This non-ionising, portable and accessible method enables early detection of osteoporosis in primary healthcare settings. The aim of this study was to assess the effectiveness of REMS in evaluating osteoporosis within primary healthcare. Methods: Bone mineral density was assessed in 86 participants trough 172 scans of the lumbar spine and femur, using REMS technology in two Portuguese primary healthcare units in Guarda. Results: In the lumbar spine evaluation, 51.2% of the participants had osteopenia and 31.4% osteoporosis; in the femur evaluation, 43.0% had osteopenia and 34.9% osteoporosis. The data indicated a significant prevalence of bone fragility. The bone mineral density estimated by radiofrequency echographic multispectrometry showed good agreement with the clinical diagnosis, suggesting that this technology is effective in the early detection of osteoporosis. Conclusions: Bone densitometry using REMS method, performed by a radiographer in primary healthcare settings, offers a viable and innovative alternative for the effective detection of osteoporosis and osteopenia.
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Affiliation(s)
- Ana Vieira
- Local Health Unit of Guarda, 6300-858 Guarda, Portugal;
- Medical Imaging and Radiotherapy Department, Coimbra Health School, Polytechnic University of Coimbra, 3045-093 Coimbra, Portugal
| | - Rute Santos
- Medical Imaging and Radiotherapy Department, Coimbra Health School, Polytechnic University of Coimbra, 3045-093 Coimbra, Portugal
- H&TRC-Health & Technology Research Centre, Coimbra Health School, Polytechnic University of Coimbra, 3045-093 Coimbra, Portugal
- Interdisciplinary Centre for the Study of Human Performance, University of Coimbra, 3004-531 Coimbra, Portugal
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RODRIGUES FREITAS G, CAPITANIO BL, WEISSHEIMER T, BARCELOS SÓ B, da SILVA EJNL, MARTINS MD, da ROSA RA, REIS SO MV. Increased Prevalence of Periapical Lesions in Osteoporosis Patients: A Systematic Review. Eur Endod J 2025; 10:94-103. [PMID: 38820458 PMCID: PMC11971693 DOI: 10.14744/eej.2024.98700] [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: 11/07/2023] [Revised: 04/15/2024] [Accepted: 05/30/2024] [Indexed: 06/02/2024] Open
Abstract
Assessing scientific literature about prevalence of periapical lesions in individuals with osteoporosis in comparison to those without osteoporosis. Systematic searches were conducted up to November 24th, 2023 in Cochrane Library, EMBASE, MEDLINE/PubMed, SCOPUS, Web of Science and Grey Literature Reports databases. Only observational studies were included. The ROBINS-E tool, a revised Cochrane instrument for assessing bias in nonrandomized exposure studies, was employed. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) tool was utilized to evaluate the certainty of the evidence. From 484 studies, three were included. One of them was categorized as having an exceptionally high risk of bias, while two were deemed to have certain concerns. Two studies reported that osteoporotic patients may have more chances to present a periapical lesion compared to non-osteoporotic patients. One study reported no differences between groups. The GRADE analysis indicated a markedly low level of certainty in the evidence. The present review indicates that osteoporotic patients may present more periapical lesions compared to non-osteoporotic patients. This statement should be cautiously interpreted and further well-designed studies are needed. (EEJ-2023-09-123).
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Affiliation(s)
- Gabiana RODRIGUES FREITAS
- Department of Conservative Dentistry, Federal University of Rio Grande do Sul (UFRGS), School of Dentistry, Porto Alegre, RS, Brazil
| | - Bárbara Luzia CAPITANIO
- Department of Conservative Dentistry, Federal University of Rio Grande do Sul (UFRGS), School of Dentistry, Porto Alegre, RS, Brazil
| | - Theodoro WEISSHEIMER
- Department of Conservative Dentistry, Federal University of Rio Grande do Sul (UFRGS), School of Dentistry, Porto Alegre, RS, Brazil
| | - Bruna BARCELOS SÓ
- Department of Conservative Dentistry, Federal University of Rio Grande do Sul (UFRGS), School of Dentistry, Porto Alegre, RS, Brazil
| | - Emmanuel João Nogueira Leal da SILVA
- Department of Endodontics, Grande Rio University (UNIGRANRIO), School of Dentistry, Rio de Janeiro, Brazil
- Department of Endodontics, Rio de Janeiro State University (UERJ), School of Dentistry, Rio de Janeiro, Brazil
| | - Manoela Domingues MARTINS
- Department of Conservative Dentistry, Federal University of Rio Grande do Sul (UFRGS), School of Dentistry, Porto Alegre, RS, Brazil
| | - Ricardo Abreu da ROSA
- Department of Conservative Dentistry, Federal University of Rio Grande do Sul (UFRGS), School of Dentistry, Porto Alegre, RS, Brazil
| | - Marcus Vinicius REIS SO
- Department of Conservative Dentistry, Federal University of Rio Grande do Sul (UFRGS), School of Dentistry, Porto Alegre, RS, Brazil
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Yordanov A, Vasileva-Slaveva M, Tsoneva E, Kostov S, Yanachkova V. Bone Health for Gynaecologists. MEDICINA (KAUNAS, LITHUANIA) 2025; 61:530. [PMID: 40142340 PMCID: PMC11944197 DOI: 10.3390/medicina61030530] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/02/2025] [Revised: 03/13/2025] [Accepted: 03/15/2025] [Indexed: 03/28/2025]
Abstract
Osteoporosis, the most common bone disorder, profoundly impacts women's health, especially during postmenopausal phases. Characterised by diminished bone mineral density (BMD), it increases the risk of fractures, affecting mobility, quality of life, and potentially mortality. The present review analyses the intricate interactions among physiological alterations, diseases, and medications that lead to bone mineral density reduction in women. It underscores the importance of gynaecologists in the prevention, diagnosis, and management of osteoporosis via early risk assessment, suitable hormone treatment, and lifestyle modifications. Essential considerations encompass the categorisation of osteoporosis into primary (age-related) and secondary (attributable to diseases or pharmacological treatments) types, with particular emphasis on predisposing conditions such as premature menopause, hormone deficits, and cancer therapies. The significance of diagnostic instruments such as DXA and novel methodologies like trabecular bone score and quantitative ultrasonography is emphasised for precise evaluation and surveillance. The review also addresses nutritional methods, physical exercise, and pharmaceutical interventions, including hormone replacement therapy (HRT), selective oestrogen receptor modulators (SERMs), and other anti-resorptive drugs, to preserve bone health. This review highlights the important role of gynaecologists in maintaining women's bone health, promoting a proactive strategy to avert osteoporosis-related complications and enhance long-term results.
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Affiliation(s)
- Angel Yordanov
- Department of Gynecologic Oncology, Medical University-Pleven, 5800 Pleven, Bulgaria
| | - Mariela Vasileva-Slaveva
- Research Institute, Medica University Pleven, 5800 Pleven, Bulgaria; (M.V.-S.); (S.K.); (V.Y.)
- Department of Breast Surgery, Specialized Hospital for Active Treatment of Obstetrics and Gynaecology “Dr Shterev”, 1330 Sofia, Bulgaria
| | - Eva Tsoneva
- Department of Reproductive Medicine, Specialized Hospital for Active Treatment of Obstetrics and Gynaecology “Dr Shterev”, 1330 Sofia, Bulgaria;
| | - Stoyan Kostov
- Research Institute, Medica University Pleven, 5800 Pleven, Bulgaria; (M.V.-S.); (S.K.); (V.Y.)
- Department of Gynecology, Hospital “Saint Anna”, Medical University—“Prof. Dr. Paraskev Stoyanov”, 9002 Varna, Bulgaria
| | - Vesselina Yanachkova
- Research Institute, Medica University Pleven, 5800 Pleven, Bulgaria; (M.V.-S.); (S.K.); (V.Y.)
- Department of Endocrinology, Specialized Hospital for Active Treatment of Obstetrics and Gynaecology “Dr Shterev”, 1330 Sofia, Bulgaria
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Fassio A, Berti A, Mantovani A, Adami G, Pollastri F, Gatti D, Bixio R, Messina V, Rossini M, Bertelle D, Bertoldo E, Galvagni I, Bortolotti R, Viapiana O. Osteoporosis and fractures in systemic vasculitides: a systematic review and meta-analysis. Front Immunol 2025; 16:1545546. [PMID: 40165972 PMCID: PMC11955673 DOI: 10.3389/fimmu.2025.1545546] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2024] [Accepted: 02/27/2025] [Indexed: 04/02/2025] Open
Abstract
Background/aim We performed a systematic review and meta-analysis of observational studies aimed at investigating the prevalence of osteoporosis and osteoporotic fractures in subjects affected by systemic vasculitides (SVs) as well as to explore their risk of osteoporosis and osteoporotic fractures when compared to healthy controls. Methods Scopus, Web of Science and PubMed were systematically searched from inception to February 2024 for observational studies investigating the prevalence of osteoporosis and fragility fractures in adults with SVs. In addition, when available, we assessed the odd ratios (OR) of prevalent osteoporosis and fragility fractures amongst subjects with SVs vs. healthy controls. Data from eligible studies were extracted, and meta-analysis was performed using a random effects model to obtain ORs with 95% confidence intervals (CIs). Subgroup analyses and meta-regressions were also performed. This study was registered in Open Science Framework (DOI: https://doi.org/10.17605/OSF.IO/3G7RJ). Results Forty studies with 23,358 individuals affected by SVs were included. The overall prevalence of osteoporosis and fragility fractures in the SV patients were respectively 14.64% (95%CI 12.21-18.89), and 17.08% (95%CI 11.42-24.78). The ORs for osteoporosis and fragility fractures in SV patients when compared with healthy controls were 2.92 (95%CI 1.72-4.98) and 2.39 (95%CI 1.34-4.26) respectively. The univariable meta-regression analysis showed a significant association between cumulative glucocorticoids' dosage (total grams) and risk of prevalent osteoporosis (estimate = 0.0995, R2 = 0.24, p=0.0194). Conclusion SVs are associated with an increased risk for osteoporosis and fragility fractures, suggesting that active vigilance and pre-emptive screening are recommended. Systematic review registration https://archive.org/details/osf-registrations-3g7rj-v1.
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Affiliation(s)
- Angelo Fassio
- Rheumatology Unit, University of Verona, Verona, Italy
| | - Alvise Berti
- Center for Medical Sciences (CISMed), Department of Cellular, Computational, and Integrative Biology (CIBIO), University of Trento, Trento, Italy
- Unit of Rheumatology, Santa Chiara Regional Hospital, Azienda Provinciale per i Servizi Sanitari (APSS), Trento, Italy
| | - Alessandro Mantovani
- Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
| | | | | | - Davide Gatti
- Rheumatology Unit, University of Verona, Verona, Italy
| | | | | | | | - Davide Bertelle
- Rheumatology Unit, University of Verona, Verona, Italy
- Rheumatology Section, Department of Medicine, Azienda Ospedaliera Friuli Occidentale, Pordenone, Italy
| | | | | | - Roberto Bortolotti
- Unit of Rheumatology, Santa Chiara Regional Hospital, Azienda Provinciale per i Servizi Sanitari (APSS), Trento, Italy
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Fan K, Hua X, Wang S, Efferth T, Tan S, Wang Z. A promising fusion: Traditional Chinese medicine and probiotics in the quest to overcome osteoporosis. FASEB J 2025; 39:e70428. [PMID: 40047492 DOI: 10.1096/fj.202403209r] [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: 12/12/2024] [Revised: 01/23/2025] [Accepted: 02/19/2025] [Indexed: 05/13/2025]
Abstract
Botanical drugs and probiotic supplements present safer alternative options for the prevention and treatment of osteoporosis (OP). However, pathological disorders of the gut microbiota and the specific properties of probiotics and traditional Chinese medicine (TCM) significantly limit their therapeutic efficacy. Given the favorable synergistic and complementary effects between probiotics and herbal medicines, a creative combination of these approaches may address the issue of their current limited efficacy. A comprehensive analysis is necessary to provide a detailed review of their potential for combination, the mechanisms behind their synergy, scientific applications, and future developments. There exists a complex relationship between gut microbiota and OP, and the underlying regulatory mechanisms are multidimensional, involving the production of pro-inflammatory metabolites, immune system disruption, and the impairment of the intestinal mucosal barrier. Furthermore, we analyzed the complex mechanisms and potential connections between probiotics, TCM, and their combined applications. We highlighted the principle of complementary gain and the substantial therapeutic potential of their organic combination, which facilitates the release of active substances in TCM, increases the bioavailability of TCM, enhances probiotic delivery efficiency, and exerts synergistic effects. The combined use of probiotics and TCM offers a safe and effective strategy for managing OP and presents an innovative and promising direction for the future development of modern phytomedicine.
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Affiliation(s)
- Kangcheng Fan
- College of Exercise and Health, Shenyang Sport University, Shenyang, China
| | - Xin Hua
- Key Laboratory of Tropical Biological Resources of Ministry of Education, School of Pharmaceutical Sciences, Hainan University, Haikou, China
| | - Shuwan Wang
- College of Exercise and Health, Shenyang Sport University, Shenyang, China
| | - Thomas Efferth
- Department of Pharmaceutical Biology, Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University, Mainz, Germany
| | - Shengnan Tan
- Key Laboratory of Tropical Biological Resources of Ministry of Education, School of Pharmaceutical Sciences, Hainan University, Haikou, China
| | - Zhuo Wang
- College of Exercise and Health, Shenyang Sport University, Shenyang, China
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Wang Y, Ma D, Wang C, Zhang X, Tang M, Hu J, Li F, Gao J, Wu Y. The Relationship Between the Heterogeneity of Lumbar Vertebral Trabecular Bone Mineral Density Distribution and Osteoporotic Vertebral Fractures. Calcif Tissue Int 2025; 116:49. [PMID: 40067443 DOI: 10.1007/s00223-025-01342-4] [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: 12/01/2024] [Accepted: 01/06/2025] [Indexed: 05/13/2025]
Abstract
This study aims to investigate the relationship between the spatial distribution and heterogeneity of lumbar vertebral trabecular volumetric bone mineral density (vBMD) and osteoporotic vertebral fractures(OVF). This retrospective study included the L1 and L2 vertebrae of 143 participants with osteoporotic vertebral fractures and 429 age- and sex-matched no-fractured controls. Spatial distribution was assessed using the superior/middle and inferior/middle ratios, while heterogeneity was indicated by the quartile coefficient of variation (QCV) and interquartile range (IQR). We used QCT to measure the integral vBMD of the vertebra and the regional vBMD in the superior, middle, and inferior subregions. QCV and IQR were computed for both integral vertebrae and three subregions using voxel values from CT images. Differences between fracture and control groups were analyzed after stratification by age and sex. T-tests and Wilcoxon rank-sum tests assessed differences in spatial distribution and heterogeneity between fracture and control groups. Conditional logistic regression was employed to evaluate the associations between spatial distribution and heterogeneity with osteoporotic vertebral fractures. Trabecular vBMD was higher in the middle subregion of the vertebrae than the superior and inferior subregions. The fracture group had lower mean integral vBMD than controls. In terms of the spatial distribution, significant differences in the superior/middle and inferior/middle ratios of the L1 vertebra were observed between the fracture and control groups in the female 40-60 years group. The superior/middle ratio of the L1 vertebra in males was positively correlated with the fracture risk. Regarding heterogeneity, the fracture group had a higher QCV than the control group. QCV was positively correlated with fracture risk, with no significant variation between sexes. The spatial distribution and heterogeneity of trabecular vBMD are crucial for predicting vertebral fracture risk. These indicators are essential for fracture risk assessment and may inform prevention and treatment strategies.
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Affiliation(s)
- Yan Wang
- Department of Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 4500052, China
| | - Duoshan Ma
- Department of Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 4500052, China
| | - Chunyu Wang
- Medical 3D Printing Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 4500052, China
| | - Xinxin Zhang
- Department of Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 4500052, China
| | - Mengna Tang
- Department of Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 4500052, China
| | - Jishuai Hu
- Department of Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 4500052, China
| | - Faxiang Li
- Department of Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 4500052, China
| | - Jianbo Gao
- Department of Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 4500052, China
| | - Yan Wu
- Department of Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 4500052, China.
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Singh A, Kumar A, Kale SY, Prakash S, Kumar V. Rehabilitation After Lower Limb Fracture Fixation in Osteoporotic Bone. Indian J Orthop 2025; 59:405-413. [PMID: 40201920 PMCID: PMC11973032 DOI: 10.1007/s43465-024-01325-x] [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: 10/25/2024] [Accepted: 11/27/2024] [Indexed: 04/10/2025]
Abstract
Background Osteoporotic fractures, particularly in the lower limbs, are a significant health burden, especially in elderly patients. With an increasing aging population globally, effective fracture fixation and rehabilitation are critical to restoring mobility and reducing complications. Objectives This study aims to review rehabilitation approaches following lower limb fracture fixation in osteoporotic bones, emphasizing the biomechanics of fracture fixation and post-surgical rehabilitation. Methods A detailed analysis of current surgical techniques for fixing osteoporotic fractures is presented, including internal fixation strategies, the use of implants, and their biomechanical performance. In addition, rehabilitation protocols post-surgery are reviewed to highlight early mobilization strategies and their impact on recovery outcomes. Results The review highlights that, despite challenges posed by osteoporotic bone quality, advancements in surgical implants and fixation techniques allow for stable fracture management. Early mobilization, while previously controversial, is increasingly supported by recent evidence, showing improved functional outcomes and reduced complications, particularly in elderly patients. Conclusions Early rehabilitation and weight-bearing strategies play a pivotal role in restoring function after osteoporotic fractures of the lower limbs. This review advocates for tailored rehabilitation protocols, considering patient age, fracture type, and the mechanical stability of the fixation.
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Affiliation(s)
- Akashdeep Singh
- Department of Orthopaedics, PGIMER, Chandigarh, 160012 India
| | - Akhilesh Kumar
- Sharnya Multispeciality Hospital, Burdwan (E), 713103 West Bengal India
| | - Sachin Yashwant Kale
- Department of Orthopaedics, Dr DY Patil School of Medicine, Nerul, Navi Mumbai, 400708 India
| | - Suraj Prakash
- National Institute of Health and Family Welfare, Munirka, New Delhi, 110067 India
| | - Vishal Kumar
- Department of Orthopaedics, PGIMER, Chandigarh, 160012 India
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Jha SS. Fragility Fracture: 10 Commandments. Indian J Orthop 2025; 59:244-255. [PMID: 40201916 PMCID: PMC11972998 DOI: 10.1007/s43465-025-01356-y] [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: 02/07/2025] [Accepted: 02/10/2025] [Indexed: 04/10/2025]
Abstract
Background Fragility fractures are a major health concern. It is a fracture that occurs from a low-impact event, such as a fall from standing height or less typically due to weakened bones. These fractures are most commonly associated with conditions like osteoporosis, where the bone density is reduced, making the bones more susceptible to get fractured. Fragility fractures often occur in older adults including post-menopausal women and commonly affect areas, such as the hip, spine, and wrist. These fractures reflect the underlying bone fragility, and following first fragility fracture, there is increased risk of getting further fractures. Apart from osteoporosis, the contributing factors have also to be considered like age, gender, nutritional deficiencies, physical activities, and medical conditions like chronic kidney disease. The other risk factors like smoking, and excessive alcohol consumption, and certain medications such as corticosteroids and anti-convulsants like sodium valproate, can overtime result into osteoporosis. Methods Fragility fractures basically revolve around the terminal management of osteoporosis and many issues have not been over emphasized. Hence, these 10 commandments have been crafted to focus on the areas which can help prevent fragility fractures or combat those cases who come with a history of fragility fractures. Results The ten commandments have crystallized into various headings, including fragility fracture-the risk factors & DEXA, subnormal turnover bone diseases, microbiota & microbiome, inflammaging including obesity, parathyroid, thyroid & testosterone, dilemmas in the management of osteoporosis in younger adults, vitamin D, calcium & albumin, pharmacologic treatment options, associated medications & alternative therapies, and monitoring. High and low turnover bone disease, dysbiosis in gut, and inflammaging are the highlights including therapy and monitoring. Conclusion Fragility fracture also known as osteoporotic fracture has significant morbidity and mortality. Management of osteoporosis has been emboldened with the existing basket of both anti-resorptive and anabolic drugs. Safety concerns on long-term use of these drugs are emerging. These ten commandments will help management strategies to concentrate on targeting therapy to persons most "at risk" of getting these fractures.
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Mariano MA, Tomori C. Fractured FRAX: Nurses' role in reckoning with racism in international osteoporosis fracture risk calculations. Nurs Outlook 2025; 73:102353. [PMID: 39933259 DOI: 10.1016/j.outlook.2025.102353] [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: 09/23/2024] [Revised: 12/08/2024] [Accepted: 01/03/2025] [Indexed: 02/13/2025]
Abstract
AIM This paper will examine racism's role in calculating fracture risk via the use of race- and ethnicity-based calculations and offer guidance for nurses to mitigate the risk of further exacerbating race-based inequities in fracture care. BACKGROUND Using race adjustments in fracture risk calculation, such as in the FRAX, reflects the history of systemic racism in nursing and medicine, particularly in screening for and treating osteoporosis. Osteoporosis-related fractures, which result in increased costs, disability, and death, are a public health problem. SOURCES OF EVIDENCE The critique examines genetic and sociohistorical evidence to illuminate the fallacy that race has biological underpinnings and outline the implications of using race in fracture risk assessment. DISCUSSION Race-based risk calculation, including assessing fracture risk, is one of the mechanisms by which the medical and healthcare sectors perpetuate systemic racism. IMPLICATIONS FOR NURSING PRACTICE AND POLICY Nurses are called to action to address the contributing role of race-based algorithms, such as the FRAX, to unequal treatment. Nurses should advocate for the removal of race in these clinical decision-making tools and case studies. Additionally, nurses should advocate for their replacement with better tools that do not use race but rather measures of structural racism to calculate risk. Policy guidance should be issued so that race, a sociohistorical tool of categorization to preserve power structures, should no longer be used as an approximation of other more relevant and precise risk factors for fractures or other diseases. CONCLUSION Nurses are critical in cultivating and implementing antiracist approaches to remediate health inequities in screening and treatment of osteoporosis and other preventable diseases.
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Affiliation(s)
- Melanie Agnes Mariano
- Johns Hopkins University School of Nursing, Baltimore, MD; Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD.
| | - Cecília Tomori
- Johns Hopkins University School of Nursing, Baltimore, MD; Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD
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Zhang X, Huang F, Liu J, Zhou Z, Yuan S, Jiang H. Molecular Mechanism of Ginsenoside Rg3 Alleviation in Osteoporosis via Modulation of KPNA2 and the NF-κB Signalling Pathway. Clin Exp Pharmacol Physiol 2025; 52:e70019. [PMID: 39821958 DOI: 10.1111/1440-1681.70019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2024] [Revised: 10/27/2024] [Accepted: 12/05/2024] [Indexed: 01/19/2025]
Abstract
Osteoporosis is mainly caused by an imbalance in osteoclast and osteoblast regulation, resulting in an imbalance in bone homeostasis. Ginsenoside Rg3 (Rg3) has been reported to have a therapeutic effect on alleviating osteoporosis. Nonetheless, the underlying mechanisms have not been completely elucidated. Herein, the molecular mechanism of Rg3 alleviation in osteoporosis was further explored. An in vitro model was established utilising the receptor activator of nuclear factor-kappaB ligand (RANKL) to induce osteoclast differentiation of RAW264.7 cells. RNA-sequencing results showed that karyopherin subunit alpha 2 (KPNA2) is one of the significantly differentially expressed genes regulated by Rg3 in RANKL-induced RAW264.7 cells. Basic experiments further suggested that KPNA2 is up-regulated in a time-dependent manner in the RANKL-induced RAW264.7 cells, while Rg3 treatment reduced its expression in a dose- and time-dependent manner. Knockdown of KPNA2 inhibited osteoclast formation and the expression of related molecules, including those in the nuclear factor kappa-B (NF-κB) pathway. The NF-κB inhibitor, JSH-23, partially abolished the impact of KPNA2 overexpression on osteoclast formation, indicating KPNA2 activates NF-κB. Furthermore, KPNA2 overexpression partially abolished the inhibitory impact of Rg3 on osteoclast formation, indicating that KPNA2 is a target of Rg3. These results suggest that KPNA2 plays a role in how Rg3 influences on osteoclast differentiation and osteoporosis through the NF-κB pathway.
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Affiliation(s)
- Xiaonan Zhang
- Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, School of Biomedical Engineering, Shenzhen University Medical School, Shenzhen, China
- Department of Orthopedics, Shenzhen Third People's Hospital, Shenzhen, China
| | - Fenglan Huang
- Department of Outpatient, Shenzhen University General Hospital, Shenzhen, China
| | - Jinzhu Liu
- Department of Orthopedics, Shenzhen Third People's Hospital, Shenzhen, China
| | - Zhenzhong Zhou
- Department of Orthopedics, Shenzhen Third People's Hospital, Shenzhen, China
| | - Shanyou Yuan
- Department of Orthopedics, Shenzhen Third People's Hospital, Shenzhen, China
| | - Haoli Jiang
- Department of Orthopedics, Shenzhen Third People's Hospital, Shenzhen, China
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Stadelmann VA, Gerossier E, Kettenberger U, Pioletti DP. Combining systemic and local osteoporosis treatments: A longitudinal in vivo microCT study in ovariectomized rats. Bone 2025; 192:117373. [PMID: 39675409 DOI: 10.1016/j.bone.2024.117373] [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: 08/22/2024] [Revised: 11/29/2024] [Accepted: 12/12/2024] [Indexed: 12/17/2024]
Abstract
INTRODUCTION Managing osteoporotic patients at immediate fracture risk is challenging, in part due to the slow and localized effects of anti-osteoporotic drugs. Combining systemic anti-osteoporotic therapies with local bone augmentation techniques offers a promising strategy, but little is known about potential interactions. We hypothesized that integrating systemic treatments with local bone-strengthening biomaterials would have an additive effect on bone density and structure. This study investigated interactions and synergies between systemic therapies and injectable biomaterials, HA2 and HA2-ZOL, designed for local bone strengthening. HA2-ZOL incorporates Zoledronate, a bisphosphonate, to enhance anti-resorptive effects. These materials were tested in an in vivo rat model of osteoporosis using microCT and histology. METHODS Thirty-six ovariectomized Wistar rats were treated systemically with vehicle (VEH), alendronate (ALN), or parathyroid hormone (PTH). One week later, their tibiae were randomly assigned to local treatment groups: HA2, HA2-ZOL, or NaCl control. Bilateral injections targeted metaphyseal trabecular bone, with microCT scans tracking changes over 8 weeks. Regions of interest (ROIs) were identified and analyzed for bone volume fraction (BV/TV), tissue mineral density (TMD), and trabecular morphology. Histological analyses were performed at week 8 to assess bone structure and mineral inclusions. RESULTS VEH animals with NaCl injections experienced marked bone loss, partially mitigated by ALN and PTH. HA2 injections increased BV/TV by factors of 2.5 to 3.4 across treatments compared to baseline, with effects confined to the injected material. HA2-ZOL amplified this response, with BV/TV increases up to 4.8-fold, particularly in VEH and PTH animals. The effects peaked at 2-4 weeks post-injection, followed by remodeling and restoration. Both local treatments increased trabecular thickness, with HA2-ZOL showing slower post-peak resorption. DISCUSSION HA2 injections significantly densified bone, independent of systemic therapy. Zoledronate in HA2-ZOL enhanced bone formation and delayed resorption in control and PTH animals, but offered no additional benefit when combined with systemic bisphosphonate. These findings support the hypothesis of an additive effect, suggesting that injectable hydrogels with localized drug delivery can complement systemic therapies by rapidly increasing local bone density, thereby potentially preventing fractures in high-risk osteoporotic patients.
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Affiliation(s)
| | - Estelle Gerossier
- Laboratory of Biomechanical Orthopedics, Institute of Bioengineering, EPFL, Lausanne, Switzerland
| | | | - Dominique P Pioletti
- Laboratory of Biomechanical Orthopedics, Institute of Bioengineering, EPFL, Lausanne, Switzerland
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Opsomer M, Iterbeke L, Borghs H, De Cuyper T, Dejaeger M, Dupont P, Claeys KG. Fractures in Hereditary Neuromuscular Disorders: Frequency, Risk Factors, and Implications. Eur J Neurol 2025; 32:e70099. [PMID: 40040345 PMCID: PMC11880628 DOI: 10.1111/ene.70099] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2024] [Revised: 01/08/2025] [Accepted: 02/20/2025] [Indexed: 03/06/2025]
Abstract
BACKGROUND Hereditary neuromuscular disorders (NMD) are associated with compromised bone health and elevated fracture risk, though data are largely lacking. OBJECTIVE This study aimed to assess the prevalence and risk factors of fractures in hereditary NMD. METHODS We conducted a retrospective study in a cohort of adult patients with diverse hereditary NMD, using data from electronic medical records. RESULTS Among 469 patients, 505 fractures were recorded, with 5.5% of patients experiencing a fracture within the past year. In the 10 years preceding study inclusion, 31.1% of all patients sustained at least one fracture. The fracture rate was 47.3/1000 patient-years. Fracture incidence was highest in the second decade of life and the first five years after symptom onset. Fracture recurrence occurred in 25.6% over the next two years. Fractures were most prevalent in patients with Duchenne muscular dystrophy, myotonic dystrophy type 1/2, and spinal muscular atrophy. Patients with Vignos scale 5-6 had the highest fracture risk. Major osteoporotic fractures accounted for 28.6%, and 71.3% were caused by low-energy trauma. Long-term complications of a fracture were present in 44.2%, with 9.0% losing ambulation. Osteoporosis was confirmed in 47.5% of DXA scans. In patients with a normal DXA scan, 66.7% experienced a subsequent fracture. Hip T-scores declined with increasing Vignos scale (r = -0.27, p = 0.001). Fracture risk factors included glucocorticoid use, alcohol abuse, recent falls, and previous emergency visits for falls (all p < 0.05). CONCLUSION This cohort exhibited a high prevalence of fractures and osteoporosis, emphasizing the need for regular bone health assessment and fracture prevention in hereditary NMD patients.
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Affiliation(s)
- Matthias Opsomer
- Department of NeurologyUniversity Hospitals LeuvenLeuvenBelgium
- Department of NeurosciencesLaboratory for Muscle Diseases and Neuropathies, KU Leuven, and Leuven Brain Institute (LBI)LeuvenBelgium
| | - Louise Iterbeke
- Department of NeurosciencesLaboratory for Muscle Diseases and Neuropathies, KU Leuven, and Leuven Brain Institute (LBI)LeuvenBelgium
| | - Herman Borghs
- Centre for Metabolic Bone DiseasesUniversity Hospitals LeuvenLeuvenBelgium
| | - Tine De Cuyper
- Centre for Metabolic Bone DiseasesUniversity Hospitals LeuvenLeuvenBelgium
| | - Marian Dejaeger
- Centre for Metabolic Bone DiseasesUniversity Hospitals LeuvenLeuvenBelgium
- Department of Geriatric MedicineUniversity Hospitals LeuvenLeuvenBelgium
- Department of Public Health and Primary CareLaboratory of Gerontology and Geriatrics, KU LeuvenLeuvenBelgium
| | - Patrick Dupont
- Department of NeurosciencesLaboratory for Cognitive Neurology, KU Leuven, and Leuven Brain Institute (LBI)LeuvenBelgium
| | - Kristl G. Claeys
- Department of NeurologyUniversity Hospitals LeuvenLeuvenBelgium
- Department of NeurosciencesLaboratory for Muscle Diseases and Neuropathies, KU Leuven, and Leuven Brain Institute (LBI)LeuvenBelgium
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Higuchi R, Uemura K, Kono S, Mae H, Takashima K, Abe H, Imagama T, Sakai T, Okada S, Hamada H. Osteoporosis screening using X-ray assessment and osteoporosis self-assessment tool for Asians in hip surgery patients. J Bone Miner Metab 2025; 43:158-165. [PMID: 39656248 PMCID: PMC11993500 DOI: 10.1007/s00774-024-01569-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/12/2024] [Accepted: 11/18/2024] [Indexed: 04/13/2025]
Abstract
OBJECTIVES As many patients with osteoporosis remain undiagnosed, we aimed to develop a simple method to efficiently screen for osteoporosis using a combination of anteroposterior hip X-ray assessment and the Osteoporosis Self-Assessment Tool for Asians (OSTA), which is calculated as (body weight - age) × 0.2. METHODS One hundred Japanese women (age: 73 ± 11 years, body weight: 54.4 ± 11.1 kg) who underwent hip surgery, anteroposterior hip X-ray, and DXA were included. Based on the DXA results of the total proximal femur, 35 cases were diagnosed with osteoporosis. Fifteen orthopaedic surgeons visually inspected the hip X-ray images and scored the suspicion of osteoporosis on a scale of 1-4 (1: very unlikely, 4: very suspicious), which is referred to as "pred-score." In addition, OSTA was calculated as a continuous variable (OSTA score). Osteoporosis was screened using the pred-score and OSTA score, and both scores were analyzed using the receiver operating characteristic curves. RESULTS The area under the curves (AUCs) of the pred-score and OSTA score were 0.626-0.875 and 0.817 across surgeons, respectively. When both scores were used, the AUC for screening osteoporosis ranged from 0.821 to 0.915 across surgeons. Significant improvement from AUCs calculated with the pred-score or OSTA score was found in 11 surgeons (73.3%). CONCLUSION The combination of X-ray assessment and OSTA can be used to screen for osteoporosis and has the potential to be used as a new simple screening tool in daily clinical practice.
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Affiliation(s)
- Ryo Higuchi
- Department of Orthopaedics, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Keisuke Uemura
- Department of Orthopaedic Medical Engineering, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
| | - Sotaro Kono
- Department of Orthopaedics, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Hirokazu Mae
- Department of Orthopaedics, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Kazuma Takashima
- Department of Orthopaedics, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Hirohito Abe
- Department of Orthopaedics, Japan Community Health Care Organization Hoshigaoka Medical Center, 4-8-1, Hoshigaoka, Hirakata, Osaka, 573-0013, Japan
| | - Takashi Imagama
- Department of Orthopaedics, Yamaguchi University Graduate School of Medicine, 1-1-1, Minamikogushi, Ube, Yamaguchi, 755-0046, Japan
| | - Takashi Sakai
- Department of Orthopaedics, Yamaguchi University Graduate School of Medicine, 1-1-1, Minamikogushi, Ube, Yamaguchi, 755-0046, Japan
| | - Seiji Okada
- Department of Orthopaedics, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Hidetoshi Hamada
- Department of Orthopaedic Medical Engineering, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan
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Ó Breasail M, Singh KP, Lithander FE, Soh S, McConvey V, McGinley J, Morris ME, Ebeling PR, Zanker J, Zengin A. Management of Osteoporosis in Parkinson's Disease: A Systematic Review of Clinical Practice Guidelines. Mov Disord Clin Pract 2025; 12:285-295. [PMID: 39704021 PMCID: PMC11952945 DOI: 10.1002/mdc3.14311] [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: 07/07/2024] [Revised: 11/20/2024] [Accepted: 12/02/2024] [Indexed: 12/21/2024] Open
Abstract
BACKGROUND Parkinson's disease (PD) is the fastest-growing neurological disorder globally. Defining features include tremor, muscular rigidity, bradykinesia, and postural instability, which in combination with nonmotor symptoms such as cognitive impairment and orthostatic hypotension increase the risk of falls. Along with low bone mineral density, fracture risk is high in PD. OBJECTIVES The aims were to identify and appraise clinical practice guidelines, consensus statements, and treatment algorithms containing recommendations for bone health in people with PD (PwP). METHODS We systematically searched 4 electroninc databases (MEDLINE, Embase, Emcare, and Web of Science) (n = 78), in addition to the websites of organizations, societies, and professional bodies focused on PD or osteoporosis (n = 28), up to April 22, 2024. RESULTS After duplicate removal, screening, and full-text review, 6 records were included. Included records were appraised using the AGREE II (Appraisal of Guidelines for Research and Evaluation) tool. All records recognized bone health as a concern in PD, yet recommendations for fracture-risk screening were inconsistent. Two of six records grouped PD under the broad category of neurological diseases. The acceptability and tolerance of anti-osteoporosis medications in PwP was discussed only in 1 record, which incorporated national osteoporosis guidelines into a PD-specific treatment algorithm. CONCLUSIONS This review highlights that despite the documented high fracture rates of PwP, health professionals do not always have adequate resources to support them when considering how to manage osteoporosis. Osteoporosis screening and management needs to be incorporated into PD treatment guidelines, and equally providing specific recommendations for PwP related to bone health in national osteoporosis guidelines should be a priority given the high burden of fracture in the patient population.
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Affiliation(s)
- Mícheál Ó Breasail
- Department of Medicine, School of Clinical Sciences at Monash Health, Faculty of Medicine, Monash Medical Centre, Nursing and Health SciencesMonash UniversityClaytonVictoriaAustralia
| | - Karan P. Singh
- Department of Medicine, School of Clinical Sciences at Monash Health, Faculty of Medicine, Monash Medical Centre, Nursing and Health SciencesMonash UniversityClaytonVictoriaAustralia
| | | | - Sze‐Ee Soh
- Department of Physiotherapy and the Rehabilitation, Ageing and Independent Living (RAIL) Research CentreMonash UniversityMelbourneVictoriaAustralia
| | | | - Jennifer McGinley
- Department of PhysiotherapyThe University of MelbourneParkvilleVictoriaAustralia
| | - Meg E. Morris
- Academic and Research Collaborative in Health (ARCH), and CERILa Trobe UniversityBundooraVictoriaAustralia
| | - Peter R. Ebeling
- Department of Medicine, School of Clinical Sciences at Monash Health, Faculty of Medicine, Monash Medical Centre, Nursing and Health SciencesMonash UniversityClaytonVictoriaAustralia
| | - Jesse Zanker
- Department of Medicine and Aged CareThe Royal Melbourne Hospital, The University of MelbourneParkvilleVictoriaAustralia
| | - Ayse Zengin
- Department of Medicine, School of Clinical Sciences at Monash Health, Faculty of Medicine, Monash Medical Centre, Nursing and Health SciencesMonash UniversityClaytonVictoriaAustralia
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