Body mass index as a predictor of fracture risk: a meta-analysis

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De Laet, C.¹; Kanis, J. A.²; Odén, A.³; Johanson, H.³; Johnell, O.⁴; Delmas, P.⁵; Eisman, J. A.⁶; Kroger, H.⁷; Fujiwara, S.⁸; Garnero, P.⁹; McCloskey, E. V.²; Mellstrom, D.¹⁰; Melton, III, L. J.¹¹; Meunier, P. J.¹²; Pols, H. A. P.; Reeve, J.¹³; Silman, A.¹⁴; Tenenhouse, A.¹⁵

Body mass index as a predictor of fracture risk: a meta-analysis

Osteoporos Int. November 2005;16(11):1330-1338

©2005 International Osteoporosis Foundation and National Osteoporosis Foundation

Affiliations

¹Scientific Institute of Public Health, Brussels, Belgium

²WHO Collaborating Centre for Metabolic Bone Diseases, University of Sheffield Medical School, Sheffield, UK

³Consulting Statistician, Gothenburg, Sweden

⁴Department of Orthopaedics, Malmö General Hospital, Malmö, Sweden

⁵INSERM Unité 149, Villejuif, France

⁶Bone and Mineral Research Program, Garvan Institute of Medical Research, St Vincent’s Hospital and University of New South Wales, Sydney, Australia

⁷Department of Surgery, Bone and Cartilage Research Unit, Kuopio University Hospital, Kuopio, Finland

⁸Department of Clinical Studies, Radiation Effects Research Foundation, Hiroshima, Japan

⁹INSERM Unité 403, Lyon, France

¹⁰Department of Geriatric Medicine, Goteborg University, Gothenburg, Sweden

¹¹Division of Epidemiology, Mayo Clinic, Rochester, USA

¹²INSERM Unit 403, Faculty R Laennec, Lyon, France

¹³Strangeway’s Research Laboratory, Cambridge, UK

¹⁴ARC Epidemiology Unit, University of Manchester, Manchester, UK

¹⁵Division of Bone Metabolism, The Montreal General Hospital, Montreal, Canada
Abstract and keywords

Low body mass index (BMI) is a well-documented risk factor for future fracture. The aim of this study was to quantify this effect and to explore the association of BMI with fracture risk in relation to age, gender and bone mineral density (BMD) from an international perspective using worldwide data. We studied individual participant data from almost 60,000 men and women from 12 prospective population-based cohorts comprising Rotterdam, EVOS/EPOS, CaMos, Rochester, Sheffield, Dubbo, EPIDOS, OFELY, Kuopio, Hiroshima, and two cohorts from Gothenburg, with a total follow-up of over 250,000 person years. The effects of BMI, BMD, age and gender on the risk of any fracture, any osteoporotic fracture, and hip fracture alone was examined using a Poisson regression model in each cohort separately. The results of the different studies were then merged. Without information on BMD, the age-adjusted risk for any type of fracture increased significantly with lower BMI. Overall, the risk ratio (RR) per unit higher BMI was 0.98 (95% confidence interval [CI], 0.97–0.99) for any fracture, 0.97 (95% CI, 0.96–0.98) for osteoporotic fracture and 0.93 (95% CI, 0.91–0.94) for hip fracture (all p <0.001). The RR per unit change in BMI was very similar in men and women ( p >0.30). After adjusting for BMD, these RR became 1 for any fracture or osteoporotic fracture and 0.98 for hip fracture (significant in women). The gradient of fracture risk without adjustment for BMD was not linearly distributed across values for BMI. Instead, the contribution to fracture risk was much more marked at low values of BMI than at values above the median. This nonlinear relation of risk with BMI was most evident for hip fracture risk. When compared with a BMI of 25 kg/m², a BMI of 20 kg/m² was associated with a nearly twofold increase in risk ratio (RR=1.95; 95% CI, 1.71–2.22) for hip fracture. In contrast, a BMI of 30 kg/m², when compared with a BMI of 25 kg/m², was associated with only a 17% reduction in hip fracture risk (RR=0.83; 95% CI, 0.69–0.99). We conclude that low BMI confers a risk of substantial importance for all fractures that is largely independent of age and sex, but dependent on BMD. The significance of BMI as a risk factor varies according to the level of BMI. Its validation on an international basis permits the use of this risk factor in case-finding strategies.

Keywords: BMI; Fractures; Meta-analysis; Osteoporosis; Prospective studies; Risk
Links

DOI: 10.1007/s00198-005-1863-y

PubMed: 15928804

WoS: 000232907600004
History

Received: 2004-12-01

Accepted: 2005-01-27

Online: 2005-06-01

Cited Works (10)

Year	Entry
1997	Kanis JA, Delmas P, Burckhardt P, Cooper C, Torgerson D; European Foundation for Osteoporosis and Bone Disease. Guidelines for diagnosis and management of osteoporosis. Osteoporos Int. July 1997;7(4):390-406.
1999	Kreiger N, Tenenhouse A, Joseph L, Mackenzie T, Poliquin S, Brown JP, Prior JC, Rittmaster RS. The Canadian Multicentre Osteoporosis study (CaMos): background, rationale, methods. Can J Aging. 1999;18(3):376-387.
2004	Johansson H, Oden A, Johnell O, Jonsson B, de Laet C, Oglesby A, McCloskey EV, Kayan K, Jalava T, Kanis JA. Optimization of BMD measurements to identify high risk groups for treatment: a test analysis. J Bone Miner Res. June 2004;19(6):906-913.
1995	Cummings SR, Nevitt MC, Browner WS, Stone K, Fox KM, Ensrud KE, Cauley J, Black D, Vogt TM; Study of Osteoporotic Fractures Research Group. Risk factors for hip fracture in white women. NEJM. March 23, 1995;332(12):767-773.
2003	Higgins JPT, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ. September 6, 2003;327(7414):557-560.
2000	Garner P, Sornay-Rendu E, Claustrat B, Delmas PD. Biochemical markers of bone turnover, endogenous hormones and the risk of fractures in postmenopausal women: the OFELY study. J Bone Miner Res. August 2000;15(8):1526-1536.
1994	Jones G, Nguyen T, Sambrook PN, Kelly PJ, Gilbert C, Eisman JA. Symptomatic fracture incidence in elderly men and women: the Dubbo Osteoporosis Epidemiology Study (DOES). Osteoporos Int. September 1994;4(5):277-282.
1996	O'Neill TW, Felsenberg D, Varlow J, Cooper C, Kanis JA, Silman AJ; The Eutopean Vertebral Osteoporosis Study Group. The prevalence of vertebral deformity in European men and women: the European Vertebral Osteoporosis study. J Bone Miner Res. July 1996;11(7):1010-1018.
1998	Melton LJ III, Atkinson EJ, O'Connor MK, O'Fallon WM, Riggs BL. Bone density and fracture risk in men. J Bone Miner Res. December 1998;13(12):1915-1923.
1996	Marshall D, Johnell O, Wedel H. Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures. BMJ. May 18, 1996;312(7041):1254-1259.

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2017	Compston J, Cooper A, Cooper C, Gittoes N, Gregson C, Harvey N, Hope S, Kanis JA, McCloskey EV, Poole KES, Reid DM, Selby P, Thompson F, Thurston A, Vine N; The National Osteoporosis Guideline Group (NOGG). UK clinical guideline for the prevention and treatment of osteoporosis. Arch Osteoporos. December 2017;12(1):1-24.
2018	Trajanoska K, Morris JA, Oei L, Zheng H-F, Evans DM, Kiel DP, Ohlsson C, Richards JB, Rivadeneira F; GEFOS/GENOMOS consortium; 23andMe research team. Assessment of the genetic and clinical determinants of fracture risk: genome wide association and mendelian randomisation study. BMJ. August 29, 2018;362:k3225.
2020	Nakamura Y, Nakano M, Suzuki T, Sato J, Kato H, Takahashi J, Shiraki M. Two adipocytokines, leptin and adiponectin, independently predict osteoporotic fracture risk at different bone sites in postmenopausal women. Bone. August 2020;137:115404.
2020	Wu P-h, Gupta T, Chang H, Petrenko D, Schafer A, Kazakia G. Soft tissue variations influence HR-pQCT density measurements in a spatially dependent manner. Bone. September 2020;138:115505.
2021	Meyer AC, Modig K. The role of having children for the incidence of and survival after hip fracture: a nationwide cohort study. Bone. April 2021;145:115873.
2021	Kim W, Nam GE, Han K, Jung J-H, Lee J, Park CM, Kim Y-H, Kim J-H, Kim SM, Park YG, Cho KH. Impact of waist circumference on the risk of vertebral fracture: a nationwide cohort study in South Korea. Bone. April 2021;145:115870.
2021	Maïmoun L, Renard E, Humbert L, Aouinti S, Mura T, Boudousq V, Lefebvre P, Mahadea K, Philibert P, de Santa-Barbara P, Avignon A, Guillaume S, Sultan A, Nocca D, Mariano-Goulart D. Modification of bone mineral density, bone geometry and volumetric BMD in young women with obesity. Bone. September 2021;150:116005.
2022	Heilmeier U, Hackl M, Schroeder F, Torabi S, Kapoor P, Vierlinger K, Eiriksdottir G, Gudmundsson EF, Harris TB, Gudnason V, Link TM, Grillari J, Schwartz AV. Circulating serum microRNAs including senescent miR-31-5p are associated with incident fragility fractures in older postmenopausal women with type 2 diabetes mellitus. Bone. May 2022;158:116308.
2023	Uragami M, Matsushita K, Shibata Y, Takata S, Karasugi T, Sueyoshi T, Masuda T, Nakamura T, Tokunaga T, Hisanaga S, Yugami M, Sugimoto K, Yonemitsu R, Ideo K, Fukuma Y, Takata K, Arima T, Kawakami J, Maeda K, Yoshimura N, Matsunaga H, Kai Y, Tanimura S, Shimada M, Tateyama M, Miyamoto K, Kubo R, Tajiri R, Tian X, Homma F, Morinaga J, Yamanouchi Y, Takebayashi M, Kajitani N, Uehara Y, Miyamoto T; Group, Kumamoto Stop OsteoPorotic Hip Fractures (K-STOP). A machine learning-based scoring system and ten factors associated with hip fracture occurrence in the elderly. Bone. November 2023;176:116865.
2020	Song J, Zhang R, Lv L, Liang J, Wang W, Liu R, Dang X. The relationship between body mass index and bone mineral density: a Mendelian randomization study. Calcif Tiss Int. November 2020;107(5):440-445.
2021	Jørgensen HS, David K, Salam S, Evenepoel P; European Renal Osteodystrophy (EUROD) workgroup, an initiative of the CKD-MBD working group of the ERA-EDTA. Traditional and non-traditional risk factors for osteoporosis in CKD. Calcif Tiss Int. April 2021;108(4):496-511.
2007	Bouxsein ML, Szulc P, Munoz F, Thrall E, Sornay‐Rendu E, Delmas PD. Contribution of trochanteric soft tissues to fall force estimates, the factor of risk, and prediction of hip fracture risk. J Bone Miner Res*. June 2007;22(6):825-831.
2014	Ballane G, Cauley JA, Luckey MM, Fuleihan GE-H. Secular trends in hip fractures worldwide: opposing trends east versus west. J Bone Miner Res. August 2014;29(8):1745-1755.
2015	Evans AL, Paggiosi MA, Eastell R, Walsh JS. Bone density, microstructure and strength in obese and normal weight men and women in younger and older adulthood. J Bone Miner Res. May 2015;30(5):920-928.
2020	Li G, Compston JE, Leslie WD, Thabane L, Papaioannou A, Lau A, Wang X, Qin C, Chen B, Chen M, Adachi JD. Relationship between obesity and risk of major osteoporotic fracture in postmenopausal women: taking frailty into consideration. J Bone Miner Res. December 2020;35(12):2355-2362.
2021	Rogmark C, Fedorowski A, Hamrefors V. Physical activity and psychosocial factors associated with risk of future fractures in middle-aged men and women. J Bone Miner Res. May 2021;36(5):852-860.
2021	Zheng R, Byberg L, Larsson SC, Höijer J, Baron JA, Michaëlsson K. Prior loss of body mass index, low body mass index, and central obesity independently contribute to higher rates of fractures in elderly women and men. J Bone Miner Res. July 2021;36(7):1288-1299.
2022	Johannesdottir F, Putman MS, Burnett-Bowie S-AM, Finkelstein JS, Yu EW, Bouxsein ML. Age-related changes in bone density, microarchitecture, and strength in postmenopausal black and white women: the SWAN longitudinal HR-pQCT study. J Bone Miner Res. January 2022;37(1):41-51.
2023	Su Y-H, Chien K-L, Yang S-H, Chia W-T, Chen J-H, Chen Y-C. Nonalcoholic fatty liver disease is associated with decreased bone mineral density in adults: a systematic review and meta-analysis. J Bone Miner Res. August 2023;38(8):1092-1103.
2023	Qu Y, Xiao C, Wu X, Zhu J, Qin C, He L, Cui H, Zhang L, Zhang W, Yang C, Yao Y, Li J, Liu Z, Zhang B, Wang W, Jiang X. Genetic correlation, shared loci, and causal association between sex hormone-binding globulin and bone mineral density: insights from a large-scale genomewide cross-trait analysis. J Bone Miner Res. November 2023;38(11):1635-1644.
2023	Leslie WD, Binkley N, Schousboe JT, McCloskey EV, Johansson H, Harvey NC, Kanis JA. Effect of BMI-discordant abdominal tissue thickness on fracture probability: a registry-based study. J Bone Miner Res. December 2023;38(12):1749-1756.
2008	Melton LJ III, Riggs BL, Leibson CL, Achenbach SJ, Camp JJ, Bouxsein ML, Atkinson EJ, Robb RA, Khosla S. A bone structural basis for fracture risk in diabetes. J Clin Endocrinol Metab. December 2008;03(12):4804-4809.
2023	Ben Tahar S, Garnier J, Eller K, DiMauro N, Piet J, Mehta S, Bajpayee AG, Shefelbine SJ. Adolescent obesity incurs adult skeletal deficits in murine induced obesity model. J Orthop Res. February 2023;41(2):386-395.
2007	Vestergaard P. Discrepancies in bone mineral density and fracture risk in patients with type 1 and type 2 diabetes: a meta-analysis. Osteoporos Int. April 2007;18(4):427-444.
2007	Kanis JA, Oden A, Johnell O, Johansson H, De Laet C, Brown J, Burckhardt P, Cooper C, Christiansen C, Cummings S, Eisman JA, Fujiwara S, Glüer C, Goltzman D, Hans D, Krieg M-A, La Croix A, McCloskey E, Mellstrom D, Melton LJ, Pols H, Reeve J, Sanders K, Schott A-M, Silman A, Torgerson D, van Staa T, Watts NB, Yoshimura N. The use of clinical risk factors enhances the performance of BMD in the prediction of hip and osteoporotic fractures in men and women. Osteoporos Int. August 2007;18(8):1033-1046.
2008	Kanis JA, Johnell O, Oden A, Johansson H, McCloskey E. FRAX™ and the assessment of fracture probability in men and women from the UK. Osteoporos Int. April 2008;19(4):385-397.
2008	Kanis JA, Burlet N, Cooper C, Delmas PD, Reginster J-Y, Borgstrom F, Rizzoli R; European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO). European guidance for the diagnosis and management of osteoporosis in postmenopausal women. Osteoporos Int. April 2008;19(4):399-428.
2008	Kanis JA, McCloskey EV, Johansson H, Strom O, Borgstrom F, Oden A. Case finding for the management of osteoporosis with FRAX^®: assessment and intervention thresholds for the UK. Osteoporos Int. October 2008;19(10):1395-1408.
2013	Kanis JA, McCloskey EV, Johansson H, Cooper C, Rizzoli R, Reginster J-Y; Scientific Advisory Board of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO); Committee of Scientific Advisors of the International Osteoporosis Foundation (IOF). European guidance for the diagnosis and management of osteoporosis in postmenopausal women. Osteoporos Int. January 2013;24(1):23-57.
2019	Kanis JA, Cooper C, Rizzoli R, Reginster J-Y; Scientific Advisory Board of the European Society for Clinical and Economic Aspects of Osteoporosis (ESCEO); Committees of Scientific Advisors and National Societies of the International Osteoporosis Foundation (IOF). European guidance for the diagnosis and management of osteoporosis in postmenopausal women. Osteoporos Int. January 2019;30(1):3-44.
2020	Hidayat K, Du X, Shi B-M, Qin L-Q. Systematic review and meta-analysis of the association between dairy consumption and the risk of hip fracture: critical interpretation of the currently available evidence. Osteoporos Int. August 2020;31(8):1411-1425.
2021	Litwic AE, Westbury LD, Ward K, Cooper C, Dennison EM. Adiposity and bone microarchitecture in the GLOW study. Osteoporos Int. April 2021;32(4):689-698.
2021	Rikkonen T, Sund R, Sirola J, Honkanen R, Poole KES, Kröger H. Obesity is associated with early hip fracture risk in postmenopausal women: a 25-year follow-up. Osteoporos Int. April 2021;32(4):769-777.
2007	Blake GM, Fogelman I. The role of DXA bone density scans in the diagnosis and treatment of osteoporosis. Postgrad Med J. August 2007;83(982):509-517.
2016	Pisani P, Renna MD, Conversano F, Casciaro E, Di Paola M, Quarta E, Muratore M, Casciaro S. Major osteoporotic fragility fractures: risk factor updates and societal impact. World J Orthop. March 18, 2016;7(3):171-181.
2010	Wright NC. The Association Between Rheumatoid Arthritis, Bone Strength, and Body Composition Within the Women's Health Initiative [PhD thesis]. University of Arizona; 2010.
2017	Billington E. Emerging Issues in Osteoporosis [MD thesis]. Auckland, New Zealand: University of Auckland; 2017.
2012	Moayyeri A. Risk Assessment for Osteoporotic Fractures Among Men and Women from a Prospective Population Study: The EPIC-Norfolk Study [PhD thesis]. Cambridge, UK: University of Cambridge; 2012.
2016	Oei L. Epidemiological, Radiological and Genetic Aspects of Endocrine Bone Diseases [PhD thesis]. Erasmus University Rotterdam; December 14, 2016.
2020	Yong JS-E. A Comparison of Physical and Behavioural Characteristics Between Postmenopausal Women With Low Bone Mass on or Off Bone Medication [Master's thesis]. Brisbane, Australia: Griffith University; August 2020.
2020	Axelsson KF. Aspects of Fracture Prevention: The Role of Fracture Liaison Services and Alendronate [PhD thesis]. University of Gothenburg; 2020.
2019	Hanne NJ. Characterizing Osteovascular Structure and Function With High Fat Diet-Induced Obesity and Stroke [PhD thesis]. North Carolina State University; 2019.
2022	Tice MJL. Loss and Modulation of Bone Matrix and Fragility During Diabetes Mellitus [PhD thesis]. Troy, NY: Rensselaer Polytechnic Institute; May 2022.
2013	Rubin KH. The Use of Risk Assessment Tools in the Clinical Management of Osteoporosis [PhD thesis]. University of Southern Denmark (SDU); July 2013.
2010	Trinward A. Osteoporosis Drugs Prevent Bone Loss, Normalize Metabolic Parameters and Negatively Correlate Bone and Fat [Master's thesis]. Stony Brook, NY: Stony Brook University; 2010.
2012	Kwaczala AT. Alendronate and PTH Differentially Modulate Bone Quality and Reduce Adiposity in an OVX Rat Model [PhD thesis]. Stony Brook, NY: Stony Brook University; December 2012.
2009	Varga P. Prediction of Distal Radius Fracture Load Using HR-PQCT-Based Finite Element Analysis [PhD thesis]. Vienna University of Technology; December 2009.
2018	George JK. Using Finite Element Models Under Multiple Loading Conditions to Improve the Association Between Radius and Tibia Microarchitecture and Prevalent Osteoporotic Vertebral Fracture [Master's thesis]. Calgary, AB: University of Calgary; May 2018.
2022	Martel DR. Contributors to Proximal Femur Fracture Force: Multiscale Considerations of Rate, Toughness, and Bone Composition [PhD thesis]. University of Waterloo; 2022.
2011	Burkhart TA. Biomechanics of the Upper Extremity in Response to Dynamic Impact Loading Indicative of a Forward Fall: An Experimental and Numerical Investigation [PhD thesis]. University of Windsor; 2011.