Kanis John A, Johansson Helena, McCloskey Eugene V, Liu Enwu, Schini Marian, Vandenput Liesbeth, Åkesson Kristina E, Anderson Fred A, Azagra Rafael, Bager Cecilie L, Beaudart Charlotte, Bischoff-Ferrari Heike A, Biver Emmanuel, Bruyère Olivier, Cauley Jane A, Center Jacqueline R, Chapurlat Roland, Christiansen Claus, Cooper Cyrus, Crandall Carolyn J, Cummings Steven R, da Silva José A P, Dawson-Hughes Bess, Diez-Perez Adolfo, Dufour Alyssa B, Eisman John A, Elders Petra J M, Ferrari Serge, Fujita Yuki, Fujiwara Saeko, Glüer Claus-Christian, Goldshtein Inbal, Goltzman David, Gudnason Vilmundur, Hall Jill, Hans Didier, Hoff Mari, Hollick Rosemary J, Huisman Martijn, Iki Masayuki, Ish-Shalom Sophia, Jones Graeme, Karlsson Magnus K, Khosla Sundeep, Kiel Douglas P, Koh Woon-Puay, Koromani Fjorda, Kotowicz Mark A, Kröger Heikki, Kwok Timothy, Lamy Olivier, Langhammer Arnulf, Larijani Bagher, Lippuner Kurt, McGuigan Fiona E A, Mellström Dan, Merlijn Thomas, Nguyen Tuan V, Nordström Anna, Nordström Peter, O Neill Terence W, Obermayer-Pietsch Barbara, Ohlsson Claes, Orwoll Eric S, Pasco Julie A, Rivadeneira Fernando, Schott Anne-Marie, Shiroma Eric J, Siggeirsdottir Kristin, Simonsick Eleanor M, Sornay-Rendu Elisabeth, Sund Reijo, Swart Karin, Szulc Pawel, Tamaki Junko, Torgerson David J, van Schoor Natasja M, van Staa Tjeerd P, Vila Joan, Wright Nicole C, Yoshimura Noriko, Zillikens M Carola, Zwart Marta, Harvey Nicholas C, Lorentzon Mattias, Leslie William D
Centre for Metabolic Bone Diseases, University of Sheffield, Sheffield, UK.
Sahlgrenska Osteoporosis Centre, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Osteoporos Int. 2025 Apr;36(4):653-671. doi: 10.1007/s00198-025-07397-1. Epub 2025 Feb 16.
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®.
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.
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.
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.
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.
在一项对来自29个前瞻性队列的个体水平数据进行的国际荟萃分析中，评估了类风湿关节炎（RA）与骨折风险之间的关系。RA与男性和女性骨折风险增加相关，这些数据将用于更新FRAX®。
RA是后续骨折的一个有充分记录的风险因素，已纳入FRAX算法。本研究的目的是通过一项国际荟萃分析，评估类风湿关节炎与后续骨折风险之间的关联及其与性别、年龄、随访时间和骨密度（BMD）的关系，以便更新FRAX。
该资源包括来自29个前瞻性队列的1,909,896名年龄在20 - 116岁之间的男性和女性，其中RA患病率为3%或更低（主要分析），以及另外17个患病率大于3%的队列（补充分析）。在每个队列和每种性别中，使用泊松回归模型的扩展来检查RA与骨折风险（任何临床骨折、骨质疏松性骨折、主要骨质疏松性骨折（MOF）和髋部骨折）之间的关联，随后对加权β系数进行随机效应荟萃分析。
在主要分析中，1.3%的个体报告患有RA。在15,683,133人年的随访期间，发生了139,002例骨折，其中27,518例为髋部骨折。RA与任何临床骨折风险增加相关（风险比[HR] 1.49，95%置信区间[CI] 1.35 - 1.65）。骨质疏松性骨折和MOF的HRs幅度相似，但髋部骨折的HRs更高（HR = 2.23；95% CI 1.85 - 2.69）。对于髋部骨折，与年龄存在显著交互作用，年龄越小HRs越高。HRs在男性和女性之间没有差异，且与糖皮质激素暴露和股骨颈BMD无关。在补充分析队列中观察到较低的HRs，特别是在那些RA明显患病率高的队列中，可能是由于RA与骨关节炎的混淆。
RA的诊断使骨折风险增加，这在很大程度上独立于BMD、性别和皮质类固醇。在未来更新风险函数的FRAX迭代中，RA应保留为风险因素，以改善骨折风险预测。
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