A meta-analysis of previous falls and subsequent fracture risk in cohort studies

Authors: VANDERPUT, LIESBETH - Australian Catholic University; JOHANSSON, HELENA - Australian Catholic University; MCCLOSKEY, EUGENE - University Of Sheffield; LIU, ENWU - Australian Catholic University; SCHINI, MARIAN - University Of Sheffield; AKESSON, KRISTINA - Lund University; ANDERSON, FRED - University Of Massachusetts; AZAGRA, RAFAEL - Autonomous University Of Barcelona; BAGER, CECILIE - Nordic Bioscience As; BEAUDART, CHARLOTTE - University Of Liege; BISCHOFF-FERRARA, HEIKE - University Of Zurich; BIVER, EMMANUEL - Geneva University Hospital; BRUYERE, OLIVIER - University Of Liege; CAULEY, JANE - University Of Pittsburgh; CENTER, JACQUELINE - Garvan Institute Of Medical Research; CHAPURLAT, ROLAND - University Of Lyon; CHRISTIANSEN, CASPER - Nordic Bioscience As; COOPER, CYRUS - University Of Southampton; CRANDALL, CAROLYN - University Of California San Francisco (UCSF); CUMMINGS, STEVEN - University Of California San Francisco (UCSF); DA SILVA, JOSE - University Of Coimbra; DAWSON-HUGHES, BESS - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; DIEZ-PEREZ, ADOLFO - Hospital Del Mar Medical Research Institute; DUFOUR, ALYSSA - Harvard Medical School; EISMAN, JOHN - Garvan Institute Of Medical Research; ELDERS, PETRA - Amsterdam Public Health Research Institute; FERRARI, SERGE - Geneva University Hospital; FUJITA, YUKI - Kindai University; FUJIWARA, SAEKO - Yasuda Women'S University; GLUER, CLAUS - University Of Kiel; GOLDSHTEIN, INBAL - Maccabi Healthcare Services; GOLTZMAN, DAVID - McGill University - Canada; GUDNASON, VILMUNDUR - Icelandic Heart Association; HALL, JILL - University Of Edinburgh; HANS, DIDIER - Lausanne University Hospital; HOFF, MARI - Norwegian University Of Science And Technology; HOLLICK, ROSEMARY - University Of Aberdeen; HUISMAN, MARTIJN - Vrije University; IKI, MASAYUKI - Kindai University; SHALOM, SOPHIA - Elisha Hospital; JONES, GRAEME - University Of Tasmania; KARLSSON, MAGNUS - Lund University; KHOSLA, SUNDEEP - Mayo Clinic College Of Medicine; KIEL, DOUGLAS - Harvard Medical School; KOH, WOON-PUAY - National University Of Singapore; KOROMANI, FJORDA - Erasmus University; KOTOWICZ, MARK - Deakin University; KROGER, HEIKKI - Kuopio University Hospital; KWOK, TIMOTHY - The Chinese University Of Hong Kong (CUHK); LAMY, OLIVIER - Lausanne University Hospital; LANGHAMMER, ARNULF - Norwegian University Of Science And Technology; LARIJANI, BAGHER - Tehran University Of Medical Sciences; LIPPUNER, KURT - Bern University Of Applied Sciences; MCGUIGAN, FIONA - Lund University; MELLSTROM, DAN - University Of Gothenburg; MERLIJN, THOMAS - Amsterdam Public Health Research Institute; NGUYEN, TUAN - University Of Technology Sydney; NORDSTROM, ANNA - The Arctic University Of Norway (UIT); NORDSTROM, PETER - Uppsala University; O'NEILL, TERRENCE - University Of Manchester; OBERMAYER-PIETSCH, BARBARA - Medical University Of Graz; OHLSSON, CLAES - University Of Gothenburg; ORWOLL, ERIC - Oregon Health & Science University; PASCO, JULIE - Deakin University; RIVADENEIRA, FERNANDO - Erasmus University; SCHOTT, ANN-MARIE - University Of Lyon; SHIROMA, ERIC - National Institute On Aging (NIA, NIH); SIGGEIRSDOTTIR, KRISTIN - Icelandic Heart Association; SIMONSICK, ELEANOR - National Institute On Aging (NIA, NIH); SORNAY-RENDU, ELIZABETH - University Of Lyon; SUND, REIJO - University Of Eastern Finland; SWART, KARIN - Amsterdam Public Health Research Institute; SZULC, PAWEL - University Of Lyon; TAMAKI, JUNKO - Osaka Medical College; TORGERSON, DAVID - York University; VAN SCHOOR, NATASJA - Amsterdam Public Health Research Institute; VAN STAA, TJEERD - University Of Manchester; VILA, JOAN - Hospital Del Mar Medical Research Institute; WAREHAM, NICKOLAS - University Of Cambridge; WRIGHT, NICOLE - University Of Alabama At Birmingham; YOSHIMURA, NIROKO - University Of Tokyo; ZILLIKENS, MARIA - Erasmus University; ZWART, MARTA - University Of Girona; HARVEY, NICHOLAS - University Of Southampton; LORENTZON, MATTIAS - Australian Catholic University; LESLIE, WILLIAM - University Of Manitoba; KANIS, JOHN - Australian Catholic University

Submitted to: Osteoporosis International
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/27/2023
Publication Date: 1/17/2024
Citation: Vanderput, L., Johansson, H., McCloskey, E.V., Liu, E., Schini, M., Akesson, K.E., Anderson, F.A., Azagra, R., Bager, C.L., Beaudart, C., Bischoff-Ferrara, H., Biver, E., Bruyere, O., Cauley, J.A., Center, J.R., Chapurlat, R., Christiansen, C., Cooper, C., Crandall, C.J., Cummings, S., da Silva, J.A., Dawson-Hughes, B., Diez-Perez, A., Dufour, A.B., Eisman, J.A., Elders, P., Ferrari, S., Fujita, Y., Fujiwara, S., Gluer, C.C., Goldshtein, I., Goltzman, D., Gudnason, V., Hall, J., Hans, D., Hoff, M., Hollick, R.J., Huisman, M., Iki, M., Shalom, S.I., Jones, G., Karlsson, M., Khosla, S., Kiel, D., Koh, W., Koromani, F., Kotowicz, M., Kroger, H., Kwok, T., Lamy, O., Langhammer, A., Larijani, B., Lippuner, K., Mcguigan, F.E., Mellstrom, D., Merlijn, T., Nguyen, T.V., Nordstrom, A., Nordstrom, P., O'Neill, T.W., Obermayer-Pietsch, B., Ohlsson, C., Orwoll, E.S., Pasco, J., Rivadeneira, F., Schott, A., Shiroma, E.J., Siggeirsdottir, K., Simonsick, E.M., Sornay-Rendu, E., Sund, R., Swart, K.M., Szulc, P., Tamaki, J., Torgerson, D., van Schoor, N.C., van Staa, T.P., Vila, J., Wareham, N.J., Wright, N.C., Yoshimura, N., Zillikens, M.C., Zwart, M., Harvey, N.C., Lorentzon, M., Leslie, W.D., Kanis, J.A. 2024. A meta-analysis of previous falls and subsequent fracture risk in cohort studies. Osteoporosis International. https://doi.org/10.1007/s00198-023-07012-1.
DOI: https://doi.org/10.1007/s00198-023-07012-1

Interpretive Summary: The relationship between self-reported falls and fracture risk was estimated in an analysis of 906,532 individuals from 46 cohorts around the globe, including the STOP IT study conducted at the USDA HNRCA. Twenty-three percent of the 906,532 participants reported falling in the past year. Having a fall in the last year was associated with a 41% increase in having a fracture in the women and a 41% increase in the men. This analysis establishes the importance of a prior fall as a risk factor for fracture and provides the justification for including a fall in the last year as a risk factor in the FRAX algorithm that is used globally to assess fracture risk.

Technical Abstract: The relationship between self-reported falls and fracture risk was estimated in an international meta-analysis of individual-level data from 46 prospective cohorts. Previous falls were associated with an increased fracture risk in women and men and should be considered as an additional risk factor in the FRAX algorithm. Introduction. Previous falls are a well-documented risk factor for subsequent fracture but have not yet been incorporated into the FRAX algorithm. The aim of this study was to evaluate, in an international meta-analysis, the association between previous falls and subsequent fracture risk and its relation to sex, age, duration of follow-up, and bone mineral density (BMD). Methods. The resource comprised 906,532 women and men (64.2% female) from 46 prospective cohorts. Previous falls were uniformly defined as any fall occurring during the previous year in 43 cohorts; the remaining three cohorts had a different question construct. The association between previous falls and fracture risk (any clinical fracture, osteoporotic fracture, major osteoporotic fracture, 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. Falls in the past year were reported in 21.3% of individuals. During a follow-up of 9,114,594 person-years, 87,518 fractures occurred of which 19,557 were hip fractures. A previous fall was associated with a significantly increased risk of any clinical fracture both in women (hazard ratio [HR] 1.41, 95% confidence interval [CI] 1.32-1.50) and men (HR 1.51, 95% CI 1.31-1.73). The HRs were of similar magnitude for osteoporotic, major osteoporotic fracture, and hip fracture. Sex significantly modified the association between previous fall and fracture risk, with predictive values being higher in men than in women (e.g., for major osteoporotic fracture, HR 1.52 (95% CI 1.27-1.82) in men vs. HR 1.30 (95% CI 1.19-1.43) in women, P for interaction = 0.0074). The HRs associated with previous falls decreased with age in women and with duration of follow-up in men and women for most fracture outcomes. Overall, there was no evidence of an interaction between falls and BMD for fracture risk. Subsequent risk for a major osteoporotic fracture increased with each additional previous fall in women and men. Conclusion. A previous self-reported fall confers an increased risk of fracture that is largely independent of BMD. Previous falls should be considered as an additional risk factor in future iterations of FRAX to improve fracture risk prediction.