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 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

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
Early online date	8 Aug 2025
DOIs	https://doi.org/10.1093/jbmr/zjaf091
Publication status	Published - Oct 2025

Funding

H.A.B.-F. has no financial interest in FRAX. For the DO-HEALTH trial cohort, Prof. H.A.B.-F. reports independent and investigator-initiated grants from European Commission Framework 7 Research Program, from the University of Zurich, from NESTEC, from Pfizer Consumer Healthcare, from Streuli Pharma, plus non-financial support from DNP. For the study cohort extension, she reports independent and investigator-initiated grants from Pfizer and from Vifor. Further, Prof. H.A.B.-F. reports non-financial support from Roche Diagnostics and personal fees from Wild, Sandoz, Pfizer, Vifor, Mylan, Roche, Meda Pharma, outside the submitted work with regard to speaker fees and travel fees. N.C.H. has received consultancy/lecture fees/honoraria/grant funding from Alliance for Better Bone Health, Amgen, MSD, Eli Lilly, Radius Health, Servier, Shire, UCB, Consilient Healthcare, Kyowa Kirin, Theramex, and Internis Pharma. R.A. has received funding for research from Instituto Carlos III of Spanish Ministry of Health, IDIAP Jordi Gol of Catalan Government and from Scientific Societies SEMFYC and SEIOMM. We are grateful to Dr. Östen Ljunggren for contributing the MrOS Sweden cohort. UK Biobank data are included under approved access agreement 3593. The authors acknowledge the Manitoba Centre for Health Policy for use of Manitoba data contained in the Population Health Research Data Repository (HIPC 2016/2017-29). The results and conclusions are those of the authors and no official endorsement by the Manitoba Centre for Health Policy, Manitoba Health, Seniors and Active Living, or other data providers is intended or should be inferred. N.C.H. acknowledges funding from the UK Medical Research Council [MC_PC_21003; MC_PC_21001] and the NIHR Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, UK. Terence O’Neill is supported by the National Institute for Health and Care Research (NIHR) Manchester Biomedical Research Centre (BRC) (NIHR203308). The WHI program is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services through 75N92021D00001, 75N92021D00002, 75N92021D00003, 75N92021D00004, 75N92021D00005. The Osteoporotic Fractures in Men (MrOS) Study is supported by National Institutes of Health funding. The following institutes provide support: the National Institute on Aging (NIA), the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), the National Center for Advancing Translational Sciences (NCATS), and NIH Roadmap for Medical Research under the following grant numbers: U01 AG027810, U01 AG042124, U01 AG042139, U01 AG042140, U01 AG042143, U01 AG042145, U01 AG042168, U01 AR066160, R01 AG066671, and UL1 TR002369. Funding for the SOF study comes from the National Institute on Aging (NIA), and the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), supported by grants (AG05407, AR35582, AG05394, AR35584, and AR35583). Funding for the Health ABC study was from the Intramural research program at the National Institute on Aging under the following contract numbers: NO1-AG-6-2101, NO1-AG-6-2103 and NO1-AG-6-2106. The Longitudinal Aging Study Amsterdam is supported by a grant from the Netherlands Ministry of Health, Welfare and Sport, Directorate of Long-Term Care. Funding for the Framingham Study comes from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) R01 AR041398 and AR061445 and National Heart, Lung, and Blood Institute Framingham Heart Study (N01-HC-25195, HHSN268201500001I). Funding for the GOS was from the Victorian Health Promotion Foundation: ID 91-0095. For the purpose of Open Access, the author has applied a Creative Commons Attribution (CC BY) licence to any Author Accepted Manuscript version arising from this submission. J.R.C. has received honoraria for speaking at educational meetings and for advisory boards from Amgen and honoraria for an advisory board from Bayer, all unrelated to this work. R.C. has no financial interest in FRAX. He has received grant funding from Amgen, UCB, Chugai, MSD, Mylan, and Medac. He has received honoraria from Amgen, UCB, Chugai, Galapagos, Biocon, Abbvie, Haoma Medica, Pfizer, Amolyt, MSD, Lilly, BMS, Novartis, Arrow, PKMed, Kyowa-Kirin, and Sanofi. A.D.-P. reports personal fees from Amgen, Lilly, Theramex, and grants from Instituto Carlos III and owns shares of Active Life Scientific, all outside the submitted work. J.A.P. has received funding from the National Health and Medical Research Council (NHMRC) Australia, and the Medical Research Future Fund (MRFF) Australia, and Amgen, all unrelated to this work.

Funders	Funder number
European Commission Framework 7
Servier
Instituto Carlos III of Spanish Ministry of Health
National Institute of Arthritis and Musculoskeletal and Skin Diseases
Shire
National Institute for Health and Care Research
Internis Pharma
UCB
Instituto Carlos III
IDIAP
Vifor
National Institute for Health Research Southampton Biomedical Research Centre
University of Southampton
Medical Research Future Fund
DNP
University Hospital Southampton NHS Foundation Trust
Eli Lilly
Radius Health
SEIOMM
Amgen
National Center for Advancing Translational Sciences
Manchester Biomedical Research Centre
National Institute on Aging
Pfizer
National Health and Medical Research Council
University of Zurich
Scientific Societies SEMFYC
U.S. Department of Health and Human Services	75N92021D00001, 75N92021D00002, 75N92021D00003, 75N92021D00004, 75N92021D00005
VicHealth	91-0095
National Institutes of Health	U01 AG042139, U01 AG042124, U01 AG042168, U01 AG042145, AG05407, UL1 TR002369, U01 AG042143, NO1-AG-6-2101, U01 AG027810, U01 AG042140, NO1-AG-6-2103, AR35584, R01 AG066671, AR35582, NO1-AG-6-2106, U01 AR066160, AR35583, AG05394
National Heart, Lung, and Blood Institute	N01-HC-25195, HHSN268201500001I
NIHR Imperial Biomedical Research Centre	NIHR203308
Medical Research Council	MC_PC_21001, MC_PC_21003
Netherlands Ministry of Health, Welfare and Sport, Directorate of Long-Term Care	R01 AR041398, AR061445

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https://pmc.ncbi.nlm.nih.gov/articles/PMC12487781/

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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{0f7d456069c44271a7a98471cdf07fa4,

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 Claus-Christian Gl{\"u}er 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 Woon-Puay Koh 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 Anne-Marie Schott 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.\}",

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, C-C, 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, W-P, 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, A-M, 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

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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