Scientific article
Meta-analysis
OA Policy
English

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

ContributorsHarvey, Nicholas Corcid; Johansson, Helena; McCloskey, Eugene Vorcid; Liu, Enwuorcid; Åkesson, Kristina Eorcid; Anderson, Fred A; Azagra-Ledesma, Rafael; Bager, Cecilie L; Beaudart, Charlotte; Bischoff-Ferrari, Heike A; Biver, Emmanuelorcid; Bruyère, Olivier; Cauley, Jane A; Center, Jacqueline Rorcid; Chapurlat, Roland; Christiansen, Claus; Cooper, Cyrusorcid; Crandall, Carolyn Jorcid; Cummings, Steven R; da Silva, José A P; Dawson-Hughes, Bessorcid; Diez-Perez, Adolfo; Dufour, Alyssa Borcid; Eisman, John Aorcid; Elders, Petra J M; Ferrari, Serge Livioorcid; Fujita, Yuki; Fujiwara, Saeko; Glüer, Claus-Christian; Goldshtein, Inbal; Goltzman, David; Gudnason, Vilmundur; Hall, Jill; Hans, Didierorcid; Hoff, Mari; Hollick, Rosemary J; Huisman, Martijn; Iki, Masayukiorcid; Ish-Shalom, Sophia; Jones, Graeme; Karlsson, Magnus Korcid; Khosla, Sundeeporcid; Kiel, Douglas Porcid; Koh, Woon-Puay; Koromani, Fjordaorcid; Kotowicz, Mark A; Kröger, Heikki; Kwok, Timothyorcid; Lamy, Olivierorcid; Langhammer, Arnulf; Larijani, Bagherorcid; Lippuner, Kurt; McGuigan, Fiona E Aorcid; Mellström, Dan; Merlijn, Thomasorcid; Nguyen, Tuan V; Nordström, Anna; Nordström, Peter; O'Neill, Terence W; Obermayer-Pietsch, Barbara; Ohlsson, Claesorcid; Orwoll, Eric Sorcid; Pasco, Julie A; Rivadeneira, Fernando; Schei, Berit; Schott, Anne-Marie; Shiroma, Eric J; Siggeirsdottir, Kristin; Simonsick, Eleanor Morcid; Sornay-Rendu, Elisabeth; Sund, Reijoorcid; Swart, Karin M A; Szulc, Pawelorcid; Tamaki, Junkoorcid; Torgerson, David J; van Schoor, Natasja M; van Staa, Tjeerd P; Vila, Joan; Wareham, Nicholas J; Wright, Nicole Corcid; Yoshimura, Noriko; Zillikens, M Carolaorcid; Zwart, Marta; Vandenput, Liesbeth; Lorentzon, Mattiasorcid; Leslie, William Dorcid; Kanis, John A
Published inJournal of bone and mineral research, vol. 40, no. 10, p. 1144-1155
Publication date2025-09-28
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 1 667 922 men and women from 32 countries (63 cohorts), followed for a total of 16.0 million person-years were studied. 293 325 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®.

Keywords
  • BMI
  • FRAX
  • Epidemiology
  • Hip fracture
  • Major osteoporotic fracture
  • Meta-analysis
  • Osteoporosis
  • Humans
  • Body Mass Index
  • Female
  • Male
  • Risk Factors
  • Middle Aged
  • Bone Density
  • Aged
  • Osteoporotic Fractures / epidemiology
  • Fractures, Bone / epidemiology
Funding
  • NHLBI NIH HHS [75N92021D00002]
  • WHI NIH HHS [75N92021D00005]
  • NHLBI NIH HHS [HHSN268201500001C]
  • NIAMS NIH HHS [R01 AR035583]
  • NCATS NIH HHS [UL1 TR002369]
  • NIAMS NIH HHS [R01 AR035584]
  • NIA NIH HHS [U01 AG042145]
  • NHLBI NIH HHS [75N92021D00001]
  • NIA NIH HHS [R01 AG005407]
  • NHLBI NIH HHS [N01 HC025195]
  • NIA NIH HHS [U01 AG042168]
  • NIA NIH HHS [U01 AG042140]
  • NIAMS NIH HHS [R01 AR035582]
  • NIA NIH HHS [U01 AG042139]
  • NIAMS NIH HHS [U01 AR066160]
  • NIA NIH HHS [R01 AG066671]
  • NIA NIH HHS [U01 AG042124]
  • NIAMS NIH HHS [R01 AR061445]
  • NIAMS NIH HHS [R01 AR041398]
  • NHLBI NIH HHS [HHSN268201500001I]
  • WHI NIH HHS [75N92021D00003]
  • NIA NIH HHS [U01 AG027810]
  • NIA NIH HHS [R01 AG005394]
  • WHI NIH HHS [75N92021D00004]
  • NIA NIH HHS [U01 AG042143]
Citation (ISO format)
HARVEY, Nicholas C et al. Body mass index and subsequent fracture risk : a meta-analysis to update FRAX. In: Journal of bone and mineral research, 2025, vol. 40, n° 10, p. 1144–1155. doi: 10.1093/jbmr/zjaf091
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Article (Published version)
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accessLevelPublic
Identifiers
Journal ISSN0884-0431
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Technical informations

Creation09/10/2025 12:28:20
First validation24/11/2025 07:46:07
Update24/11/2025 07:46:07
Status update24/11/2025 07:46:07
Last indexation24/11/2025 07:46:08
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