Body mass index and subsequent fracture risk: a meta-analysis to update FRAX
Nicholas C. Harvey, Helena Johansson, Eugène McCloskey, Enwu Liu, Kristina Åkesson, Fred Anderson, Rafael Azagra, Cecilie L. Bager, Charlotte Beaudart, Heike A. Bischoff‐Ferrari, Emmanuel Biver, Olivier Bruyère, Jane A. Cauley, Roland Chapurlat, Claus Christiansen, Cyrus Cooper, Carolyn Crandall, Steven R. Cummings, José António Pereira da Silva, Bess Dawson‐Hughes, Adolfo Díez‐Pérez, Alyssa B. Dufour, John A. Eisman, Petra J. M. Elders, Serge Ferrari, Yuki Fujita, Saeko Fujiwara, Claus‐Christian Glüer, Inbal Goldshtein, David Goltzman, Vilmundur Guðnason, Jill Hall, Didier Hans, Mari Hoff, Rosemary 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. McGuigan, Dan Mellström, Thomas Merlijn, Tuan V. Nguyen, Anna Nordström, Peter Nordström, Terence W O’Neill, Barbara Obermayer‐Pietsch, Claes Ohlsson, Eric Orwoll, Julie A. Pasco, Fernando Rivadeneira, Berit Schei, Anne‐Marie Schott, Eric J. Shiroma, Kristín Siggeirsdóttir, Eleanor M. Simonsick, Elisabeth Sornay‐Rendu, Reijo Sund, Karin M. A. Swart, Paweł Szulc, Junko Tamaki, David Torgerson, Natasja M. van Schoor, Tjeerd 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
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®.