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Body mass index and subsequent fracture risk: a meta-analysis to update FRAX

  • Nicholas C. Harvey*
  • , Helena Johansson
  • , Eugene V. McCloskey
  • , Enwu Liu
  • , Kristina E. Åkesson
  • , Fred A. Anderson
  • , Rafael Azagra-Ledesma
  • , 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, Berit Schei, 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, M. Carola Zillikens, Marta Zwart, Liesbeth Vandenput, Mattias Lorentzon, William D. Leslie, John A. Kanis
*Corresponding author for this work
  • MRC Lifecourse Epidemiology Unit
  • University of Southampton
  • University of Sheffield
  • South Australian Health And Medical Research Institute
  • Lund University
  • University of Massachusetts Medical School
  • Autonomous University of Barcelona
  • Generalitat de Catalunya
  • GROICAP
  • PRECIOSA-Fundación Para La Investigación
  • Nordic Bioscience AS
  • Universite de Namur
  • University of Basel
  • University of Zurich
  • University of Geneva
  • University of Liege
  • University of Pittsburgh
  • Garvan Institute of Medical Research
  • University of New South Wales
  • Universite Claude Bernard Lyon 1
  • University of Oxford
  • University of California at Los Angeles
  • California Pacific Medical Center
  • University of Coimbra
  • Tufts University
  • Children's Healthcare of Atlanta
  • Harvard University
  • University of Notre Dame Australia
  • Amsterdam UMC
  • Kansai Medical University
  • Yasuda Women's University
  • Universitätsklinikum Schleswig-Holstein Campus Kiel
  • Maccabi Healthcare Services
  • Tel Aviv University
  • McGill University
  • Icelandic Heart Association
  • University of Iceland
  • University of Edinburgh
  • University of Lausanne
  • Norwegian University of Science and Technology
  • University of Aberdeen
  • Vrije Universiteit Amsterdam
  • Kindai University
  • Elisha Hospital
  • University of Tasmania
  • Mayo Clinic Rochester, MN
  • National University of Singapore
  • Agency for Science, Technology and Research, Singapore
  • Erasmus University Rotterdam
  • Deakin University
  • Barwon Health
  • University of Melbourne
  • University of Eastern Finland
  • Chinese University of Hong Kong
  • Nord-Trøndelag Hospital Trust
  • Tehran University of Medical Sciences
  • University of Bern
  • University of Gothenburg
  • Sahlgrenska University Hospital
  • University of Technology Sydney
  • Tam Anh Hospital
  • University of Tromsø – The Arctic University of Norway
  • Mid Sweden University
  • Uppsala University
  • Manchester University NHS Foundation Trust
  • University of Manchester
  • Medical University of Graz
  • Oregon Health and Science University
  • Monash University
  • National Institutes of Health
  • Janus Rehabilitation
  • National Institute on Aging Intramural Research Program
  • Université de Lyon
  • PHARMO Institute, Utrecht
  • Osaka Medical and Pharmaceutical University
  • University of York
  • Epidemiology and Data Science, Amsterdam UMC Location Vrije Universiteit
  • Hospital del Mar
  • MRC Epidemiology Unit Insitute of Meatabolic Science University of Cambridge
  • Tulane University
  • The University of Tokyo
  • University of Girona
  • Institut Universitari d'Investigació en Atenció Primària Jordi Gol (IDIAP Jordi Gol)
  • University of Manitoba

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Abstract

The aim of this international meta-analysis was to quantify the predictive value of BMI for incident fracture and relationship of this risk with age, sex, follow-up time, and BMD. A total of 1667922 men and women from 32 countries (63 cohorts), followed for a total of 16.0 million person-years were studied. 293325 had FN BMD measured (2.2 million person-years follow-up). An extended Poisson model in each cohort was used to investigate relationships between WHO-defined BMI categories (Underweight: <18.5 kg/m2; Normal: 18.5-24.9 kg/m2; Overweight: 25.0-29.9 kg/m2; Obese I: 30.0-34.9 kg/m2; Obese II: ≥35.0 kg/m2) and risk of incident osteoporotic, major osteoporotic and hip fracture (HF). Inverse-variance weighted β-coefficients were used to merge the cohort-specific results. For the subset with BMD available, in models adjusted for age and follow-up time, the hazard ratio (95% CI) for HF comparing underweight with normal weight was 2.35 (2.10-2.60) in women and for men was 2.45 (1.90-3.17). Hip fracture risk was lower in overweight and obese categories compared to normal weight [obese II vs normal: women 0.66 (0.55-0.80); men 0.91 (0.66-1.26)]. Further adjustment for FN BMD T-score attenuated the increased risk associated with underweight [underweight vs normal: women 1.69 (1.47-1.96); men 1.46 (1.00-2.13)]. In these models, the protective effects of overweight and obesity were attenuated, and in both sexes, the direction of association reversed to higher fracture risk in Obese II category [Obese II vs Normal: women 1.24 (0.97-1.58); men 1.70 (1.06-2.75)]. Results were similar for other fracture outcomes. Underweight is a risk factor for fracture in both men and women regardless of adjustment for BMD. However, while overweight/obesity appeared protective in base models, they became risk factors after additional adjustment for FN BMD, particularly in the Obese II category. This effect in the highest BMI categories was of greater magnitude in men than women. These results will inform the second iteration of FRAX®.

Original languageEnglish
Pages (from-to)1144-1155
Number of pages12
JournalJournal of Bone and Mineral Research
Volume40
Issue number10
DOIs
Publication statusPublished - 1 Oct 2025

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

  1. SDG 3 - Good Health and Well-being
    SDG 3 Good Health and Well-being

Keywords

  • BMI
  • FRAX
  • epidemiology
  • hip fracture
  • major osteoporotic fracture
  • meta-analysis
  • osteoporosis

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