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

Liesbeth Vandenput, Helena Johansson, Eugene V. McCloskey, Enwu Liu, Marian Schini, 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. CummingsJosé 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 M. A. Swart, Pawel Szulc, Junko Tamaki, David J. Torgerson, Natasja M. van Schoor, Tjeerd P. van Staa, Joan Vila, Nicholas J. Wareham, Nicole C. Wright, Noriko Yoshimura, MCarola Zillikens, Marta Zwart, Nicholas C. Harvey, Mattias Lorentzon, William D. Leslie, John A. Kanis* (Corresponding Author)

*Corresponding author for this work

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Abstract

Summary
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 906,359 women and men (66.9% 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 21.4% of individuals. During a follow-up of 9,102,207 person-years, 87,352 fractures occurred of which 19,509 were hip fractures. A previous fall was associated with a significantly increased risk of any clinical fracture both in women (hazard ratio (HR) 1.42, 95% confidence interval (CI) 1.33–1.51) and men (HR 1.53, 95% CI 1.41–1.67). 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 1.53 (95% CI 1.27–1.84) in men vs. HR 1.32 (95% CI 1.20–1.45) in women, P for interaction = 0.013). 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. 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.

Conclusions
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.
Original languageEnglish
Article number469–494
Number of pages26
JournalOsteoporosis International
Volume35
Early online date17 Jan 2024
DOIs
Publication statusPublished - 1 Mar 2024

Bibliographical note

NC Harvey acknowledges funding from the UK Medical Research Council (MC_PC_21003; MC_PC_21001). The WHI program is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services through 75N92021D00001, 75N92021D00002, 75N92021D00003, 75N92021D00004, and 75N92021D00005. Funding for the MrOS USA study comes from the National Institute on Aging (NIA), the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), the National Center for Advancing Translational Sciences (NCATS), and NIH Roadmap for Medical Research under the following grant numbers: U01 AG027810, U01 AG042124, U01 AG042139, U01 AG042140, U01 AG042143, U01 AG042145, U01 AG042168, U01 AR066160, and UL1 TR000128. Funding for the SOF study comes from the National Institute on Aging (NIA), and the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), supported by grants (AG05407, AR35582, AG05394, AR35584, and AR35583). Funding for the Health ABC study was from the Intramural research program at the National Institute on Aging under the following contract numbers: NO1-AG-6–2101, NO1-AG-6–2103, and NO1-AG-6–2106.

Keywords

  • fracture risk
  • hip fracture
  • major osteoporotic fracture
  • meta-analysis
  • previous falls
  • Risk factors

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