Body mass index and subsequent fracture risk: a meta-analysis to update FRAX.
Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 2025 ; 40: 1144-1155.
Harvey NC, Johansson H, McCloskey EV, Liu E, Åkesson KE, Anderson FA, Azagra-Ledesma R, Bager CL, Beaudart C, Bischoff-Ferrari HA, Biver E, Bruyère O, Cauley JA, Center JR, Chapurlat R, Christiansen C, Cooper C, Crandall CJ, Cummings SR, da Silva JAP, Dawson-Hughes B, Diez-Perez A, Dufour AB, Eisman JA, Elders PJM, Ferrari S, Fujita Y, Fujiwara S, Glüer CC, Goldshtein I, Goltzman D, Gudnason V, Hall J, Hans D, Hoff M, Hollick RJ, Huisman M, Iki M, Ish-Shalom S, Jones G, Karlsson MK, Khosla S, Kiel DP, Koh WP, Koromani F, Kotowicz MA, Kröger H, Kwok T, Lamy O, Langhammer A, Larijani B, Lippuner K, McGuigan FEA, Mellström D, Merlijn T, Nguyen TV, Nordström A, Nordström P, O'Neill TW, Obermayer-Pietsch B, Ohlsson C, Orwoll ES, Pasco JA, Rivadeneira F, Schei B, Schott AM, Shiroma EJ, Siggeirsdottir K, Simonsick EM, Sornay-Rendu E, Sund R, Swart KMA, Szulc P, Tamaki J, Torgerson DJ, van Schoor NM, van Staa TP, Vila J, Wareham NJ, Wright NC, Yoshimura N, Zillikens MC, Zwart M, Vandenput L, Lorentzon M, Leslie WD, Kanis JA
DOI : 10.1093/jbmr/zjaf091
PubMed ID : 40795319
PMCID : PMC12487781
URL : https://academic.oup.com/jbmr/article/40/10/1144/8228261
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®.