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ARS Home » Northeast Area » Boston, Massachusetts » Jean Mayer Human Nutrition Research Center On Aging » Research » Publications at this Location » Publication #424533
Research Project: Diet Quality and Physical Activity for Healthy Aging and Chronic Disease Mitigation

Location: Jean Mayer Human Nutrition Research Center On Aging

Title: Rheumatoid arthritis and subsequent fracture risk: an individual person meta-analysis to update FRAX

Author
item KANIS, JOHN - University Of Sheffield Medical School
item JOHANSSON, HELENA - University Of Gothenburg
item MCCLOSKEY, EUGENE - University Of Sheffield
item LIU, ENWU - South Australia Health And Medical Research Institute (SAHMRI)
item SCHINI, MARIAN - University Of Sheffield
item VANDENPUT, LIESBETH - University Of Gothenburg
item AKESSON, KRISTINA - Lund University
item ANDERSON, FRED - University Of Massachusetts
item AZAGRA, RAFAEL - Autonomous University Of Barcelona
item BAGER, CECILIE - Nordic Bioscience As
item BEAUDART, CHARLOTTE - Maastricht University
item BISHCHOFF-FERRARI, HEIKE - University Of Zurich
item BIVER, EMMANUEL - University Of Geneva
item BRUYERE, OLIVIER - University Of Liege
item CAULEY, JANE - University Of Pittsburgh
item CENTER, JACQUELINE - Garvan Institute Of Medical Research
item CHAPURLAT, ROLAND - Université Claude Bernard Lyon 1
item CHRISTIANSEN, CLAUS - Nordic Bioscience As
item COOPER, CYRUS - University Of Southampton
item CRANDALL, CAROLYN - University Of California
item CUMMINGS, STEVEN - University Of California San Francisco (UCSF)
item DA SILVA, JOSE - University Of Coimbra
item DAWSON-HUGHES, BESS - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item DIEZ-PEREZ, ADOLF - Autonomous University Of Barcelona
item DUFOUR, ALYSSA - Harvard University
item EISMAN, JOHN - Garvan Institute Of Medical Research
item ELDERS, PETRA - Amsterdam Public Health Research Institute
item FERRARI, SERGE - University Of Geneva
item FUJITA, YUKI - Kansai Research Center
item FUJIWARA, SAEKO - Yasuda Women'S University
item GLUER, CLAUS CHRISTIAN - University Of Kiel
item GOLDSHTIEN, INBAL - Tel Aviv University
item GOLTZMAN, DAVID - McGill University - Canada
item GUDNASON, VILMUNDUR - University Of Iceland
item HALL, JILL - University Of Edinburgh
item HANS, DIDIER - University Of Lausanne
item HOFF, MARI - Norwegian University Of Science And Technology
item HOLLICK, ROSEMARY - University Of Aberdeen
item HUISMAN, MARTIJN - Vu University Medical Center
item IKI, MASAYUKI - Kindai University
item ISH SHALOM, SOPHIA - Elisha Hospital
item JONES, GRAEME - University Of Tasmania
item KARLSSON, MAGNUS - Lund University
item KHOSLA, SUNDEEP - Mayo Clinic
item KIEL, DOUGLAS - Marcus Institute For Aging Research
item KOH, WOON PUAY - National University Of Singapore
item KOROMANI, FJORDA - Erasmus Medical Center
item KOTOWICZ, MARK - Deakin University
item KROGER, HEIKKI - Kuopio University Hospital
item KWOK, TIMOTHY - The Chinese University Of Hong Kong (CUHK)
item LAMY, OLIVIER - University Of Lausanne
item LANGHAMMER, ARNULG - Norwegian University Of Science And Technology
item LARIJANI, BAGHER - Tehran University Of Medical Sciences
item LIPPUNER, KURT - University Of Bern
item MCGUIGAN, FIONA - Lund University
item MELLSTROM, DAN - University Of Gothenburg
item MERLJIN, THOMAS - Amsterdam Public Health Research Institute
item NGUYEN, TUAN - University Of Technology Sydney
item NORDSTROM, ANNA - Uppsala University
item NORDSTROM, PETER - Uppsala University
item O'NEILL, TERENCE - University Of Manchester
item OBERMAYER-PIETSCH, BARBARA - Medical University Of Graz
item OHLSSON, CLAES - University Of Gothenburg
item ORWOLL, ERIC - Oregon Health & Science University
item PASCO, JULIE - Deakin University
item RIVADENEIRA, FERNANDO - Erasmus Medical Center
item SCHOTT, ANNE MARIE - Université Claude Bernard Lyon 1
item SHIROMA, ERIC - National Institute On Aging (NIA, NIH)
item SIGGEIRSDOTTIR, KRISTIN - Janus Rehabilitation
item SIMONSICK, ELEANOR - National Institute On Aging (NIA, NIH)
item SORNAY-RENDU, ELISABETH - University Of Lyon
item SUND, REIJO - University Of Eastern Finland
item SWART, KARIN - Pharmo Institute For Drug Outcomes Research
item SZULC, PAWEL - University Of Lyon
item TAMAKI, JUNKO - Educational Foundation Of Osaka Medical And Pharmaceutical University
item TORGENSON, DAVID - University Of York
item VAN SCHOOR, NATASJA - Institut Universitari D'Investigacio En Atencio Primaria Jordi Gol
item VAN STAA, TJEERD - University Of Manchester
item VILA, JOAN - Hospital Del Mar Medical Research Institute
item WRIGHT, NICOLE - University Of Alabama
item YOSHIMURA, NORIKO - University Of Tokyo
item ZILLIKENS, M. CAROLA - Erasmus Medical Center
item ZWART, MARTA - Institut Universitari D'Investigacio En Atencio Primaria Jordi Gol
item HARVEY, NICHOLAS - University Of Southampton
item LORENTZON, MATTIAS - University Of Gothenburg
item LESLIE, WILLIAM - University Of Manitoba

Submitted to: Osteoporosis International
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/8/2025
Publication Date: 2/16/2025
Citation: Kanis, J.A., Johansson, H., Mccloskey, E.V., Liu, E., Schini, M., Vandenput, L., Akesson, K., Anderson, F.A., Azagra, R., Bager, C., Beaudart, C., Bishchoff-Ferrari, H., Biver, E., Bruyere, O., Cauley, J.A., Center, J.R., Chapurlat, R., Christiansen, C., Cooper, C., Crandall, C.J., Cummings, S.R., Da Silva, J.A., Dawson-Hughes, B., Diez-Perez, A., Dufour, A.B., Eisman, J.A., Elders, P.J., Ferrari, S., Fujita, Y., Fujiwara, S., Gluer, C., Goldshtien, I., Goltzman, D., Gudnason, V., Hall, J., Hans, D., Hoff, M., Hollick, R., Huisman, M., Iki, M., Ish Shalom, S., Jones, G., Karlsson, M.K., Khosla, S., Kiel, D.P., Koh, W., Koromani, F., Kotowicz, M., Kroger, H., Kwok, T., Lamy, O., Langhammer, A., Larijani, B., Lippuner, K., Mcguigan, F.E., Mellstrom, D., Merljin, T., Nguyen, T.V., Nordstrom, A., Nordstrom, P., O'Neill, T., Obermayer-Pietsch, B., Ohlsson, C., Orwoll, E., Pasco, J.A., Rivadeneira, F., Schott, A., Shiroma, E.J., Siggeirsdottir, K., Simonsick, E.M., Sornay-Rendu, E., Sund, R., Swart, K., Szulc, P., Tamaki, J., Torgenson, D.J., Van Schoor, N.M., Van Staa, T., Vila, J., Wright, N.C., Yoshimura, N., Zillikens, M., Zwart, M., Harvey, N.C., Lorentzon, M., Leslie, W.D. 2025. Rheumatoid arthritis and subsequent fracture risk: an individual person meta-analysis to update FRAX. Osteoporosis International. https://doi.org/10.1007/s00198-025-07397-1.
DOI: https://doi.org/10.1007/s00198-025-07397-1

Interpretive Summary: FRAX is an algorithm for predicting fracture risk that is widely used around the world. Rheumatoid arthritis is a recognized risk factor for fracture. 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 with a view to updating the FRAX algorithm. The study comprised 1,909,896 men and women, aged 20-116 years, from 29 prospective cohorts including the Boston STOP IT study. During 15,683,133 person-years of follow-up, 139,002 fractures occurred. RA was associated with a significant 50% increase in risk of any fracture and an even greater increase in risk of hip fracture. This analysis of data from cohorts around the world justifies the continued inclusion of rheumatoid arthritis in the FRAX calculator in order to improve fracture risk prediction.

Technical Abstract: Summary 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. Introduction 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. Methods 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. Results 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. Conclusions 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.