Osteoporosis International最新文献

{"title":"Protective role of irisin on bone in osteoporosis: a systematic review of rodent studies.","authors":"Jia Li, Xiaochen Fu, Hongfeng Shi, Jiapeng Jing, Qinzhi Zheng, Zhuo Xu","doi":"10.1007/s00198-025-07470-9","DOIUrl":"https://doi.org/10.1007/s00198-025-07470-9","url":null,"abstract":"<p><p>Osteoporosis is defined as a bone disease that is characterized by a reduction in bone mass and an elevated risk of fracture. Irisin, which is regulated by peroxisome proliferator-activated receptor γ coactivator-1α (PGC1α), is a muscle-derived protein that is induced by exercise. A number of studies have indicated that irisin has the capacity to stimulate bone formation and decrease bone resorption, which plays a crucial role in bone metabolism. Regular exercise has been demonstrated to be an effective method for maintaining and enhancing bone health, with irisin emerging as a key regulatory molecule in this process. In light of these findings, irisin represents a promising approach for the treatment of osteoporosis. Animal studies are an essential part of the clinical trial process, as they are used to assess the efficacy and potential risks associated with proposed interventions. The objective of this review was to conduct a systematic review of animal studies and discuss the effects and mechanisms of irisin on bone in osteoporosis. A systematic search was conducted across eight databases, resulting in the identification, data extraction, and quality assessment of 27 articles. The results demonstrate that irisin can restore the steady state of bone homeostasis through the activation or inhibition of multiple pathways. It can ameliorate the microstructural damage and bone turnover caused by osteoporosis; improve the response to bone mechanical stress; promote the proliferation, differentiation, and mineralization of osteoblasts; and play an important role in exercise-based prevention and treatment of osteoporosis. Furthermore, irisin can attenuate inflammatory changes in bone and participate in the regulation of cell death. This review was registered at PROSPERO (CRD42024539678).</p>","PeriodicalId":19638,"journal":{"name":"Osteoporosis International","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143796131","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between vertebral fractures and brain volume: insights from a community cohort study.","authors":"Koji Nakajima, Chiaki Horii, Hiroyasu Kodama, Tomohiko Shirokoshi, Akitoshi Ogawa, Takahiro Osada, Seiki Konishi, Yasushi Oshima, Toshiko Iidaka, Shigeyuki Muraki, Hiroyuki Oka, Hiroshi Kawaguchi, Toru Akune, Hiroshi Hashizume, Hiroshi Yamada, Munehito Yoshida, Kozo Nakamura, Masaaki Shojima, Sakae Tanaka, Noriko Yoshimura","doi":"10.1007/s00198-025-07403-6","DOIUrl":"10.1007/s00198-025-07403-6","url":null,"abstract":"<p><p>Investigating vertebral fractures and brain structure, we found significant gray matter volume reductions in the right hippocampus, amygdala, and parahippocampal gyrus, especially in males. These findings emphasize the importance of integrating skeletal and neural health in osteoporosis management.</p><p><strong>Purpose: </strong>Vertebral fractures (VF) due to osteoporosis impact morbidity and quality of life in the elderly. The relationship between VF and changes in brain structure remains underexplored. This study aimed to investigate the association between VF and gray matter volume (GMV) reductions in specific brain regions and to explore potential sex differences.</p><p><strong>Methods: </strong>Data from 1,751 participants (571 males, 1,180 females; mean age 64.9, range 18-97) in the fourth survey of the population-based Research on Osteoarthritis/Osteoporosis Against Disability study (2015-2016) were used. Participants were classified into those with and without VF (VF + and VF - groups) based on Genant's semiquantitative method, assessed by spine radiographs. Voxel-based morphometry was applied to MRI images to measure GMV, and a general linear model analysis was performed to compare GMV between groups, adjusting for age, sex, total brain volume, and Mini-Mental State Examination scores as covariates. Additionally, a two-way analysis of variance was conducted on the significant GMV cluster, with sex and VF presence as independent variables, to explore interaction effects.</p><p><strong>Results: </strong>The VF+ group consisted of 113 participants, while the VF- group included 1,638 participants. The analysis identified a significant cluster with reduced GMV in the VF + group compared to the VF - group. This cluster included the right hippocampus, right amygdala, and right parahippocampal gyrus. Further analysis revealed that males in the VF + group exhibited more pronounced GMV reductions in the significant cluster compared to females.</p><p><strong>Conclusion: </strong>These findings suggest that VF is associated with significant reductions in brain regions critical for memory, emotional processing, and visuospatial memory, with more severe effects observed in males.</p>","PeriodicalId":19638,"journal":{"name":"Osteoporosis International","volume":" ","pages":"627-636"},"PeriodicalIF":4.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12064467/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143189626","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rethinking sunlight: balancing the benefits of sun exposure and vitamin D supplementation.","authors":"Berkay Yalçınkaya, Hilmi Berkan Abacıoğlu, Ahmet Furkan Çolak, Alp Çetin","doi":"10.1007/s00198-025-07420-5","DOIUrl":"10.1007/s00198-025-07420-5","url":null,"abstract":"","PeriodicalId":19638,"journal":{"name":"Osteoporosis International","volume":" ","pages":"755-756"},"PeriodicalIF":4.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143365375","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Elevated baseline CTX levels predict enhanced therapeutic efficacy of zoledronic acid in augmenting lumbar spine bone mineral density among Chinese osteoporosis patients.","authors":"Qing Zhang, Wenxue Gao, Xiaojuan Xu, Ran Cui, Bin Su","doi":"10.1007/s00198-025-07448-7","DOIUrl":"10.1007/s00198-025-07448-7","url":null,"abstract":"<p><p>This study examined the link between baseline CTX levels and zoledronic acid's effectiveness in boosting bone density in osteoporosis patients. Among 472 Chinese patients, higher initial CTX levels correlated with greater lumbar spine bone density improvement after treatment. However, no such correlation was found for hip or femoral neck bones. This suggests CTX levels may aid in treatment selection for lumbar spine, though further research is needed. The findings have clinical implications for optimizing osteoporosis treatment.</p><p><strong>Purpose: </strong>To elucidate the correlation between baseline CTX levels and the therapeutic efficacy of zoledronic acid in augmenting bone mineral density (BMD) among individuals with osteoporosis.</p><p><strong>Methods: </strong>This study studied patients diagnosed with primary osteoporosis who were hospitalized at least twice and received annual zoledronic acid therapy. Patients were stratified into three groups based on their initial CTX levels prior to zoledronic acid administration. ANOVA was employed to compare BMD alterations across the groups. Generalized estimating equations (GEE) were utilized to analyze the relationship between baseline CTX levels and subsequent BMD changes post-zoledronic acid treatment. Statistical analyses were conducted using SPSS version 26.0.</p><p><strong>Results: </strong>A total of 472 patients were evaluated and categorized into three cohorts according to their initial CTX levels, arranged in ascending order. Notably, group 3, characterized by the highest initial CTX levels, demonstrated a significantly more pronounced increase in lumbar spine BMD compared to the other two groups. Specifically, when group 1 served as the reference, group 3 exhibited a 0.4-unit elevation in lumbar spine T-score. Conversely, no discernible relationship was observed between baseline CTX levels and BMD changes in the hip or femoral neck following zoledronic acid treatment.</p><p><strong>Conclusions: </strong>Our findings among a Chinese population indicate that elevated CTX levels, particularly exceeding 0.480 ng/ml, are notably associated with enhanced therapeutic efficacy of zoledronic acid in boosting lumbar spine BMD. However, this correlation appears less robust with respect to improvements in hip and femoral neck BMD.</p>","PeriodicalId":19638,"journal":{"name":"Osteoporosis International","volume":" ","pages":"707-714"},"PeriodicalIF":4.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143557495","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identifying proximal humerus fractures: an algorithmic approach using registers and radiological visit data.","authors":"Tomi Nissinen, Reijo Sund, Sanna Suoranta, Heikki Kröger, Sami P Väänänen","doi":"10.1007/s00198-025-07414-3","DOIUrl":"10.1007/s00198-025-07414-3","url":null,"abstract":"<p><p>In this study, we show that combining register and radiological visit data enables more accurate automated identification of proximal humerus fractures compared to traditional register analysis. In a cohort of 11,863 post-menopausal women, our proposed approach improved the coverage of identified fractures from 74 to 81%.</p><p><strong>Purpose: </strong>The aim of this study was to investigate how reliably proximal humerus fractures can be identified from different administrative datasets without manual review.</p><p><strong>Method: </strong>Using the national medical registers, namely the Care Register for Health Care and the Register for Primary Health Care Visits, as well as the regional radiological image archive PACS, we developed algorithms for automated identification of proximal humerus fractures. In addition to these sources, we used data from patient records as well as from the self-reports gathered by the Kuopio Osteoporosis Risk Factor and Prevention Study (OSTPRE) to establish a gold standard of fractures for validating the algorithms. This gold standard included proximal humerus fractures for a cohort of 11,863 post-menopausal women living in the Kuopio region between 2004 and 2022.</p><p><strong>Results: </strong>We report the national registers' yearly accuracy in identifying proximal humerus fractures. During the studied 19-year period, the registers' coverage initially improved but then settled at 75%. We show that the image archive provides almost complete coverage of radiographs for the fracture cases, but excluding false positives poses a challenge. In addition, we propose a simple approach that combines register and radiography visit data to improve the accuracy of automated fracture identification. Our algorithm improves the coverage from 74 to 81% and reduces the false discovery rate from 8 to 7% compared to the traditional register analysis.</p><p><strong>Conclusion: </strong>The proposed approach enables a more reliable way of identifying proximal humerus fractures from administrative data. This study contributes to the objective of automatically tracking all types of fragility fractures in large datasets.</p>","PeriodicalId":19638,"journal":{"name":"Osteoporosis International","volume":" ","pages":"645-651"},"PeriodicalIF":4.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12064595/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143365307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Author response to the letter to the editor \"Comment on: The risk of fragility fractures in men with prostate cancer treated with androgen deprivation therapy\" (OSIN-D-24-01632).","authors":"M M van Oostwaard, J P van den Bergh, C E Wyers","doi":"10.1007/s00198-024-07331-x","DOIUrl":"10.1007/s00198-024-07331-x","url":null,"abstract":"","PeriodicalId":19638,"journal":{"name":"Osteoporosis International","volume":" ","pages":"763-764"},"PeriodicalIF":4.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143425633","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advancing trabecular bone score (TBS): clinical performance of TBS version 4.0 with direct correction for soft tissue thickness-the osteolaus study.","authors":"Guillaume Gatineau, Karen Hind, Enisa Shevroja, Elena Gonzalez-Rodriguez, Olivier Lamy, Didier Hans","doi":"10.1007/s00198-025-07421-4","DOIUrl":"10.1007/s00198-025-07421-4","url":null,"abstract":"<p><p>This study compared TBS v4.0, which uses DXA-derived tissue thickness corrections, with TBS v3, which adjusts using BMI. TBS v4.0 improved soft tissue adjustments and maintained fracture risk prediction equivalence with TBS v3, enhancing applicability across diverse body compositions/phenotypes. Direct tissue thickness adjustment increases TBS's utility in osteoporosis assessment and management.</p><p><strong>Purpose: </strong>This study aimed to compare trabecular bone score (TBS) version 4.0, which uses direct tissue thickness correction via DXA measurements, with TBS version 3, which adjusts for soft tissues using body mass index (BMI). The objective was to assess the performance of TBS v4.0 compared to v3, for bone health evaluation and fracture risk assessment across diverse body compositions.</p><p><strong>Methods: </strong>Data from the OsteoLaus cohort were analyzed. Associations between TBS, BMI, DXA-measured tissue thickness, visceral fat (VFAT), and android fat were examined using regression and correlation analyses. Machine learning, including Random Forest (RF) and SHapley Additive exPlanations (SHAP), explored TBS changes between versions. Five-year fracture risk was assessed using FRAX adjustment, and logistic regression.</p><p><strong>Results: </strong>TBS v3 correlated with BMI (r = 0.110, p < 0 .001), VFAT mass (r =  - 0.162, p < 0 .001), and soft tissue thickness (r =  - 0.165, p < 0.001). TBS v4.0 demonstrated weaker correlations with BMI (r =  - 0.057, p > 0.999), VFAT Mass (r =  - 0.067, p > 0.779), and soft tissue thickness (r =  - 0.114, p = 0.019). Differences between TBS versions were investigated with SHapley Additive exPlanations (SHAP) and explained by BMI, tissue thickness, VFAT, and gynoid fat. Logistic regression and Delong's test revealed no significant differences in vertebral fracture prediction between the two TBS versions (p = 0.564). FRAX adjustments were highly consistent between versions (r = 0.994, p < 0.001), with no evidence of calibration bias (p = 0.241).</p><p><strong>Conclusion: </strong>TBS v4.0 enhances the adjustment for regional soft tissue effects and results suggest comparable vertebral fracture risk prediction to TBS v3. Explainable AI provided insights into the contributions of BMI, tissue thickness, visceral fat, and gynoid fat to the observed changes between TBS versions. Incorporating direct tissue thickness adjustment improves TBS applicability across diverse body sizes and compositions.</p>","PeriodicalId":19638,"journal":{"name":"Osteoporosis International","volume":" ","pages":"715-724"},"PeriodicalIF":4.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12064620/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143557489","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Changing trends in bisphosphonate therapy: a twenty-five-year surveillance in a single US integrated healthcare system.","authors":"Joan C Lo, Malini Chandra, Mehreen M Khan, Joshua Barzilay, Laura D Carbone, Susan M Ott, Robert A Adler, John T Schousboe, Elisha A Garcia, Deborah Low, Rita L Hui","doi":"10.1007/s00198-024-07372-2","DOIUrl":"10.1007/s00198-024-07372-2","url":null,"abstract":"<p><p>In a single, large integrated US healthcare system, bisphosphonate treatment initiation for fracture prevention among older adults shifted towards higher-risk populations over a 25-year time period (1998-2022). The temporal trends among women and men who initiated treatment reflected changing practice patterns and both primary and secondary fracture prevention efforts.</p><p><strong>Introduction: </strong>While bisphosphonate (BP) drugs remain first-line for fracture prevention, treatment has changed over time. This study examines trends over 25 years among adults initiating BP in a single healthcare system.</p><p><strong>Methods: </strong>Among adults aged 50-89 years who initiated alendronate, risedronate, ibandronate, or zoledronate in Kaiser Permanente Northern California during 1998-2022, age, sex, race and ethnicity, and fracture history were examined. Findings across 5-year periods were evaluated.</p><p><strong>Results: </strong>A total of 212,289 adults (86.0% women) initiated BP during 1998-2022. After 2008, a much lower proportion of adults who initiated BP were age < 65 years. Across successive 5-year periods, the percentages of women who were age < 65 years were 35.1%, 35.2%, 24.1%, 18.8%, and 17.8%. Among men, these percentages were 26.9%, 25.4%, 17.6%, 12.6%, and 4.7%. In later years, sustained or increasing numbers of adults initiating BP coincided with electronic health record targets for BMD screening (since 2016 for women, 2017-2019 for men), an impact greater for men. The proportions with prior fracture among women initiating BP increased from 21-24% (1998-2007) to 35-38% (2008-2022) after implementing a secondary fracture prevention program for women in 2008. Among men, this proportion increased from 28 to 37%, 40%, and 47% during successive 5-year periods in 1998-2017 (the secondary fracture prevention program for men began in 2015) but fell to 26% in 2018-2022 after BMD screening targeted older men.</p><p><strong>Conclusions: </strong>In a large primary care population of adults initiating BP, greater treatment of older adults and those with prior fracture highlights the key role of targeted fracture prevention initiatives, sustaining treatment efforts.</p>","PeriodicalId":19638,"journal":{"name":"Osteoporosis International","volume":" ","pages":"741-747"},"PeriodicalIF":4.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12064395/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143365344","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identifying rare variants in genes related to bone phenotypes in a cohort of postmenopausal women.","authors":"J D Patiño-Salazar, D Ovejero, M Gabernet, N Martínez-Gil, E Alcaide-Consuegra, L Mellibovsky, X Nogués, D Grinberg, S Balcells, R Rabionet, N Garcia-Giralt","doi":"10.1007/s00198-025-07413-4","DOIUrl":"10.1007/s00198-025-07413-4","url":null,"abstract":"<p><p>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.</p><p><strong>Purpose: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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).</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":19638,"journal":{"name":"Osteoporosis International","volume":" ","pages":"637-644"},"PeriodicalIF":4.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12064449/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143365310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rheumatoid arthritis and subsequent fracture risk: an individual person meta-analysis to update FRAX.","authors":"John A Kanis, Helena Johansson, Eugene V McCloskey, Enwu Liu, Marian Schini, Liesbeth Vandenput, Kristina E Åkesson, Fred A Anderson, Rafael Azagra, Cecilie L Bager, Charlotte Beaudart, Heike A Bischoff-Ferrari, Emmanuel Biver, Olivier Bruyère, Jane A Cauley, Jacqueline R Center, Roland Chapurlat, Claus Christiansen, Cyrus Cooper, Carolyn J Crandall, Steven R Cummings, José A P da Silva, Bess Dawson-Hughes, Adolfo Diez-Perez, Alyssa B Dufour, John A Eisman, Petra J M Elders, Serge Ferrari, Yuki Fujita, Saeko Fujiwara, Claus-Christian Glüer, Inbal Goldshtein, David Goltzman, Vilmundur Gudnason, Jill Hall, Didier Hans, Mari Hoff, Rosemary J Hollick, Martijn Huisman, Masayuki Iki, Sophia Ish-Shalom, Graeme Jones, Magnus K Karlsson, Sundeep Khosla, Douglas P Kiel, Woon-Puay Koh, Fjorda Koromani, Mark A Kotowicz, Heikki Kröger, Timothy Kwok, Olivier Lamy, Arnulf Langhammer, Bagher Larijani, Kurt Lippuner, Fiona E A McGuigan, Dan Mellström, Thomas Merlijn, Tuan V Nguyen, Anna Nordström, Peter Nordström, Terence W O Neill, Barbara Obermayer-Pietsch, Claes Ohlsson, Eric S Orwoll, Julie A Pasco, Fernando Rivadeneira, Anne-Marie Schott, Eric J Shiroma, Kristin Siggeirsdottir, Eleanor M Simonsick, Elisabeth Sornay-Rendu, Reijo Sund, Karin Swart, Pawel Szulc, Junko Tamaki, David J Torgerson, Natasja M van Schoor, Tjeerd P van Staa, Joan Vila, Nicole C Wright, Noriko Yoshimura, M Carola Zillikens, Marta Zwart, Nicholas C Harvey, Mattias Lorentzon, William D Leslie","doi":"10.1007/s00198-025-07397-1","DOIUrl":"10.1007/s00198-025-07397-1","url":null,"abstract":"<p><p>The relationship between rheumatoid arthritis (RA) and fracture risk was estimated in an international meta-analysis of individual-level data from 29 prospective cohorts. RA was associated with an increased fracture risk in men and women, and these data will be used to update FRAX®.</p><p><strong>Introduction: </strong>RA is a well-documented risk factor for subsequent fracture that is incorporated into the FRAX algorithm. The aim of this study was to evaluate, in an international meta-analysis, the association between rheumatoid arthritis and subsequent fracture risk and its relation to sex, age, duration of follow-up, and bone mineral density (BMD) with a view to updating FRAX.</p><p><strong>Methods: </strong>The resource comprised 1,909,896 men and women, aged 20-116 years, from 29 prospective cohorts in which the prevalence of RA was 3% or less (primary analysis) and an additional 17 cohorts with a prevalence greater than 3% (supplementary analysis). The association between RA and fracture risk (any clinical fracture, osteoporotic fracture, major osteoporotic fracture (MOF), and hip fracture) was examined using an extension of the Poisson regression model in each cohort and each sex, followed by random-effects meta-analyses of the weighted beta coefficients.</p><p><strong>Results: </strong>In the primary analysis, RA was reported in 1.3% of individuals. During 15,683,133 person-years of follow-up, 139,002 fractures occurred, of which 27,518 were hip fractures. RA was associated with an increased risk of any clinical fracture (hazard ratio [HR] 1.49, 95% confidence interval [CI] 1.35-1.65). The HRs were of similar magnitude for osteoporotic fracture and MOF but higher for hip fracture (HR = 2.23; 95% CI 1.85-2.69). For hip fracture, there was a significant interaction with age with higher HRs at younger ages. HRs did not differ between men and women and were independent of exposure to glucocorticoids and femoral neck BMD. Lower HRs were observed in the supplementary analysis cohorts, particularly in those with a high apparent prevalence of RA, possibly from conflation of RA with osteoarthritis.</p><p><strong>Conclusions: </strong>A diagnosis of RA confers an increased risk of fracture that is largely independent of BMD, sex, and corticosteroids. RA should be retained as a risk factor in future iterations of FRAX with updated risk functions to improve fracture risk prediction.</p>","PeriodicalId":19638,"journal":{"name":"Osteoporosis International","volume":" ","pages":"653-671"},"PeriodicalIF":4.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143425641","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}