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

doi:10.1093/jbmr/zjaf091

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 SilvaBess 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

Internal Medicine

Research output: Contribution to journal › Article › Academic › peer-review

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 language	English
Pages (from-to)	1144-1155
Number of pages	12
Journal	Journal of Bone and Mineral Research
Volume	40
Issue number	10
DOIs	https://doi.org/10.1093/jbmr/zjaf091
Publication status	Published - Oct 2025

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Publisher Copyright:
© The Author(s) 2025. Published by Oxford University Press on behalf of the American Society for Bone and Mineral Research.

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Body mass index and subsequent fracture riskFinal published version, 1.6 MBLicence: CC BY

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Harvey, N. C., Johansson, H., McCloskey, E. V., Liu, E., Åkesson, K. E., Anderson, F. A., Azagra-Ledesma, R., Bager, C. L., Beaudart, C., Bischoff-Ferrari, H. A., Biver, E., Bruyère, O., Cauley, J. A., Center, J. R., Chapurlat, R., Christiansen, C., Cooper, C., Crandall, C. J., Cummings, S. R., ... Kanis, J. A. (2025). Body mass index and subsequent fracture risk: a meta-analysis to update FRAX. Journal of Bone and Mineral Research, 40(10), 1144-1155. https://doi.org/10.1093/jbmr/zjaf091

@article{5fe89600b99b4a37b6616dbbb1059f68,

title = "Body mass index and subsequent fracture risk: a meta-analysis to update FRAX",

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{\textregistered}.",

author = "Harvey, \{Nicholas C.\} and Helena Johansson and McCloskey, \{Eugene V.\} and Enwu Liu and {\AA}kesson, \{Kristina E.\} and Anderson, \{Fred A.\} and Rafael Azagra-Ledesma and Bager, \{Cecilie L.\} and Charlotte Beaudart and Bischoff-Ferrari, \{Heike A.\} and Emmanuel Biver and Olivier Bruy{\`e}re and Cauley, \{Jane A.\} and Center, \{Jacqueline R.\} and Roland Chapurlat and Claus Christiansen and Cyrus Cooper and Crandall, \{Carolyn J.\} and Cummings, \{Steven R.\} and \{Da Silva\}, \{Jos{\'e} A.P.\} and Bess Dawson-Hughes and Adolfo Diez-Perez and Dufour, \{Alyssa B.\} and Eisman, \{John A.\} and Elders, \{Petra J.M.\} and Serge Ferrari and Yuki Fujita and Saeko Fujiwara and Gl{\"u}er, \{Claus Christian\} and Inbal Goldshtein and David Goltzman and Vilmundur Gudnason and Jill Hall and Didier Hans and Mari Hoff and Hollick, \{Rosemary J.\} and Martijn Huisman and Masayuki Iki and Sophia Ish-Shalom and Graeme Jones and Karlsson, \{Magnus K.\} and Sundeep Khosla and Kiel, \{Douglas P.\} and Koh, \{Woon Puay\} and Fjorda Koromani and Kotowicz, \{Mark A.\} and Heikki Kr{\"o}ger and Timothy Kwok and Olivier Lamy and Arnulf Langhammer and Bagher Larijani and Kurt Lippuner and McGuigan, \{Fiona E.A.\} and Dan Mellstr{\"o}m and Thomas Merlijn and Nguyen, \{Tuan V.\} and Anna Nordstr{\"o}m and Peter Nordstr{\"o}m and O{\textquoteright}Neill, \{Terence W.\} and Barbara Obermayer-Pietsch and Claes Ohlsson and Orwoll, \{Eric S.\} and Pasco, \{Julie A.\} and Fernando Rivadeneira and Berit Schei and Schott, \{Anne Marie\} and Shiroma, \{Eric J.\} and Kristin Siggeirsdottir and Simonsick, \{Eleanor M.\} and Elisabeth Sornay-Rendu and Reijo Sund and Swart, \{Karin M.A.\} and Pawel Szulc and Junko Tamaki and Torgerson, \{David J.\} and \{Van Schoor\}, \{Natasja M.\} and \{Van Staa\}, \{Tjeerd P.\} and Joan Vila and Wareham, \{Nicholas J.\} and Wright, \{Nicole C.\} and Noriko Yoshimura and Zillikens, \{M. Carola\} and Marta Zwart and Liesbeth Vandenput and Mattias Lorentzon and Leslie, \{William D.\} and Kanis, \{John A.\}",

note = "Publisher Copyright: {\textcopyright} The Author(s) 2025. Published by Oxford University Press on behalf of the American Society for Bone and Mineral Research.",

year = "2025",

month = oct,

doi = "10.1093/jbmr/zjaf091",

language = "English",

volume = "40",

pages = "1144--1155",

journal = "Journal of Bone and Mineral Research",

issn = "0884-0431",

publisher = "Oxford University Press",

number = "10",

}

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 2025, 'Body mass index and subsequent fracture risk: a meta-analysis to update FRAX', Journal of Bone and Mineral Research, vol. 40, no. 10, pp. 1144-1155. https://doi.org/10.1093/jbmr/zjaf091

TY - JOUR

T1 - Body mass index and subsequent fracture risk

T2 - a meta-analysis to update FRAX

AU - Harvey, Nicholas C.

AU - Johansson, Helena

AU - McCloskey, Eugene V.

AU - Liu, Enwu

AU - Åkesson, Kristina E.

AU - Anderson, Fred A.

AU - Azagra-Ledesma, Rafael

AU - Bager, Cecilie L.

AU - Beaudart, Charlotte

AU - Bischoff-Ferrari, Heike A.

AU - Biver, Emmanuel

AU - Bruyère, Olivier

AU - Cauley, Jane A.

AU - Center, Jacqueline R.

AU - Chapurlat, Roland

AU - Christiansen, Claus

AU - Cooper, Cyrus

AU - Crandall, Carolyn J.

AU - Cummings, Steven R.

AU - Da Silva, José A.P.

AU - Dawson-Hughes, Bess

AU - Diez-Perez, Adolfo

AU - Dufour, Alyssa B.

AU - Eisman, John A.

AU - Elders, Petra J.M.

AU - Ferrari, Serge

AU - Fujita, Yuki

AU - Fujiwara, Saeko

AU - Glüer, Claus Christian

AU - Goldshtein, Inbal

AU - Goltzman, David

AU - Gudnason, Vilmundur

AU - Hall, Jill

AU - Hans, Didier

AU - Hoff, Mari

AU - Hollick, Rosemary J.

AU - Huisman, Martijn

AU - Iki, Masayuki

AU - Ish-Shalom, Sophia

AU - Jones, Graeme

AU - Karlsson, Magnus K.

AU - Khosla, Sundeep

AU - Kiel, Douglas P.

AU - Koh, Woon Puay

AU - Koromani, Fjorda

AU - Kotowicz, Mark A.

AU - Kröger, Heikki

AU - Kwok, Timothy

AU - Lamy, Olivier

AU - Langhammer, Arnulf

AU - Larijani, Bagher

AU - Lippuner, Kurt

AU - McGuigan, Fiona E.A.

AU - Mellström, Dan

AU - Merlijn, Thomas

AU - Nguyen, Tuan V.

AU - Nordström, Anna

AU - Nordström, Peter

AU - O’Neill, Terence W.

AU - Obermayer-Pietsch, Barbara

AU - Ohlsson, Claes

AU - Orwoll, Eric S.

AU - Pasco, Julie A.

AU - Rivadeneira, Fernando

AU - Schei, Berit

AU - Schott, Anne Marie

AU - Shiroma, Eric J.

AU - Siggeirsdottir, Kristin

AU - Simonsick, Eleanor M.

AU - Sornay-Rendu, Elisabeth

AU - Sund, Reijo

AU - Swart, Karin M.A.

AU - Szulc, Pawel

AU - Tamaki, Junko

AU - Torgerson, David J.

AU - Van Schoor, Natasja M.

AU - Van Staa, Tjeerd P.

AU - Vila, Joan

AU - Wareham, Nicholas J.

AU - Wright, Nicole C.

AU - Yoshimura, Noriko

AU - Zillikens, M. Carola

AU - Zwart, Marta

AU - Vandenput, Liesbeth

AU - Lorentzon, Mattias

AU - Leslie, William D.

AU - Kanis, John A.

PY - 2025/10

Y1 - 2025/10

N2 - 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®.

AB - 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®.

UR - https://www.scopus.com/pages/publications/105017660752

U2 - 10.1093/jbmr/zjaf091

DO - 10.1093/jbmr/zjaf091

M3 - Article

C2 - 40795319

AN - SCOPUS:105017660752

SN - 0884-0431

VL - 40

SP - 1144

EP - 1155

JO - Journal of Bone and Mineral Research

JF - Journal of Bone and Mineral Research

IS - 10

ER -

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

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