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ARS Home » Northeast Area » Boston, Massachusetts » Jean Mayer Human Nutrition Research Center On Aging » Research » Publications at this Location » Publication #425133
Research Project: Diet Quality and Physical Activity for Healthy Aging and Chronic Disease Mitigation

Location: Jean Mayer Human Nutrition Research Center On Aging

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

Author
item HARVEY, NICOLAS - University Of Southampton
item JOHANSSON, HELENA - University Of Gothenburg
item MCCLOSKEY, EUGENE - University Of Sheffield
item LIU, ENWU - South Australia Health And Medical Research Institute (SAHMRI)
item AKESSON, KRISTINA - Lund University
item ANDERSON, FRED - University Of Massachusetts
item AZAGRA, RAFAEL - Autonomous University Of Barcelona
item BAGER, CECILIE - Nordic Bioscience As
item BEAUDART, CHARLOTTE - Maastricht University
item BISHCHOFF-FERRARI, HEIKE - University Of Zurich
item BIVER, EMMANUEL - University Of Geneva
item BRUYERE, OLIVIER - University Of Liege
item CAULEY, JANE - University Of Pittsburgh
item CENTER, JACQUELINE - Garvan Institute Of Medical Research
item CHAPURLAT, ROLAND - Université Claude Bernard Lyon 1
item CHRISTIANSEN, CLAUS - Nordic Bioscience As
item COOPER, CYRUS - University Of Southampton
item CRANDALL, CAROLYN - University Of California (UCLA)
item CUMMINGS, STEVEN - University Of California San Francisco (UCSF)
item DA SILVA, JOSE - University Of Coimbra
item DAWSON-HUGHES, BESS - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item DIEZ-PEREZ, ADOLFO - Autonomous University Of Barcelona
item DUFOUR, ALYSSA - Harvard Medical School
item EISMAN, JOHN - Garvan Institute Of Medical Research
item ELDERS, PETRA - Amsterdam Public Health Research Institute
item FERRARI, SERGE - University Of Geneva
item FUJITA, YUKI - Kansai Research Center
item GLUER, CLAUS CHRISTIAN - University Of Kiel
item GOLDSHTEIN, INBAL - Tel Aviv University
item GOLTZMAN, DAVID - McGill University - Canada
item GUDNASON, VILMUNDUR - University Of Iceland
item HALL, JILL - University Of Edinburgh
item HANS, DIDIER - University Of Lausanne
item HOFF, MARI - Norwegian University Of Science And Technology
item HOLICK, ROSEMARY - University Of Aberdeen
item HUISMAN, MARTIJN - Vrijie University (VU)
item IKI, MASAYUKI - Kindai University
item ISH SHALOM, SOPHIA - Elisha Hospital
item JONES, GRAEME - University Of Tasmania
item KARLSSON, MAGNUS - Lund University
item KHOSLA, SUNDEEP - Mayo Clinic
item KIEL, DOUGLAS - Marcus Institute For Aging Research
item KOH, WOON PUAY - National University Of Singapore
item KOROMANI, FJORDA - Erasmus Medical Center
item KOTOWICZ, MARK - Deakin University
item KROGER, HEIKKI - Kuopio University Hospital
item KWOK, TIMOTHY - The Chinese University Of Hong Kong (CUHK)
item LAMY, OLIVER - Lausanne University Hospital
item LANGHAMMER, ARNULF - Norwegian University Of Science And Technology
item LARIJANI, BAGHER - Tehran University Of Medical Sciences
item LIPPPUNER, KURT - University Of Bern
item MCGUIGAN, FIONA - Lund University
item MELLSTROM, DAN - University Of Gothenburg
item MERLJIN, THOMAS - Amsterdam Public Health Research Institute
item NGUYEN, TUAN - University Of Technology Sydney
item NORDSTROM, ANNA - Uppsala University
item NORDSTROM, PETER - Uppsala University
item O'NEILL, TERENCE - University Of Manchester
item OBERMAYER-PIETSCH, BARBARA - Medical University Of Graz
item OHLSSON, CLAES - University Of Gothenburg
item ORWOLL, ERIC - Oregon Health & Science University
item PASCO, JULIE - Deakin University
item RIVADENEIRA, FERNANDO - Erasmus Medical Center
item SCHOTT, ANNE MARIE - Université Claude Bernard Lyon 1
item SHIROMA, ERIC - National Institute On Aging (NIA, NIH)
item SIGGEIRSDOTTIR, KRISTIN - Janus Rehabilitation
item SIMONSICK, ELEANOR - National Institute On Aging (NIA, NIH)
item SORNAY-RENDU, ELISABETH - University Of Lyon
item SUND, REIJO - University Of Eastern Finland
item SWART, KARIN - Pharmo Institute For Drug Outcomes Research
item SZULC, PAWEL - University Of York
item TAMAKI, JUNKO - University Medical Center Amsterdam
item TORGERSON, DAVID - Hospital Del Mar Medical Research Institute
item VAN SCHOOR, NATASJA - University Of Cambridge
item VAN STAA, TJEERD - University Of Alabama
item VILLA, JOAN - University Of Tokyo
item WAREHAM, NICHOLAS - University Of Cambridge
item WRIGHT, NICOLE - University Of Alabama
item YOSHIMURA, NORIKO - University Of Tokyo
item ZILLIKENS, M. CAROLA - Erasmus Medical Center
item VANDENPUT, LIESBETH - University Of Gothenburg
item LORENTZON, MATTIAS - Sahlgrenska University Hospital
item LESLIE, WILLIAM - University Of Manitoba
item KANIS, JOHN - University Of Sheffield Medical School

Submitted to: Osteoporosis International
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/20/2025
Publication Date: 8/8/2002
Citation: Harvey, N.C., Johansson, H., Mccloskey, E.V., Liu, E., Akesson, K., Anderson, F.A., Azagra, R., Bager, C., Beaudart, C., Bishchoff-Ferrari, H., Biver, E., Bruyere, O., Cauley, J.A., Center, J.R., Chapurlat, R., Christiansen, C., Cooper, C., Crandall, C.J., Cummings, S.R., Da Silva, J.A., Dawson-Hughes, B., Diez-Perez, A., Dufour, A.B., Eisman, J.A., Elders, P.J., Ferrari, S., Fujita, Y., Gluer, C., Goldshtein, I., Goltzman, D., Gudnason, V., Hall, J., Hans, D., Hoff, M., Holick, R., Huisman, M., Iki, M., Ish Shalom, S., Jones, G., Karlsson, M.K., Khosla, S., Kiel, D.P., Koh, W., Koromani, F., Kotowicz, M., Kroger, H., Kwok, T., Lamy, O., Langhammer, A., Larijani, B., Lipppuner, K., Mcguigan, F.E., Mellstrom, D., Merljin, T., Nguyen, T.V., Nordstrom, A., Nordstrom, P., O'Neill, T., Obermayer-Pietsch, B., Ohlsson, C., Orwoll, E., Pasco, J.A., Rivadeneira, F., Schott, A., Shiroma, E.J., Siggeirsdottir, K., Simonsick, E.M., Sornay-Rendu, E., Sund, R., Swart, K., Szulc, P., Tamaki, J., Torgerson, D.J., Van Schoor, N.M., Van Staa, T., Villa, J., Wareham, N.J., Wright, N.C., Yoshimura, N., Zillikens, M., Vandenput, L., Lorentzon, M., Leslie, W.D., Kanis, J.A. 2002. Body mass index and subsequent fracture risk: A meta-analysis to update FRAX. Osteoporosis International. 40(10):1144-1155. https://doi.org/10.1093/jbmr/zjaf091.
DOI: https://doi.org/10.1093/jbmr/zjaf091

Interpretive Summary: Body mass index, calculated as weight divided by height squared, is an accepted indirect measure of obesity for population studies and as a clinical risk factor in the assessment of fracture risk. The World Health Organization-defined body mass index categories are: underweight: <18.5 kg/m2, normal weight: 18.5-24.9 kg/m2, overweight: 25.0-29.9 kg/m2, obese I: 30.0-34.9 kg/m2, and obese II: = 35.0 kg/m2. To quantify the extent to which body mass index can predict fracture risk, we carried out a meta-analysis of data from 63 cohorts, including the Boston STOP IT trial, to assess the association in 1,666,716 older men and women from 63 countries. We found that being underweight was associated with a significantly increased risk of a hip fracture in the men and in the women. In both sexes, hip fracture risk was significantly lower in overweight and obese categories compared to normal weight; however, risk increased after taking into account the hip bone mineral density of these participants. In conclusion, being normal weight is associated with lower hip fracture risk than being either under- or over-weight. These findings will inform the next version of the widely used fracture risk calculator, FRAX

Technical Abstract: The aim of this international meta-analysis was to quantify the predictive value of BMI for incident fracture and to explore the relationship of this risk with age, sex, follow-up time and bone mineral density (BMD). The analysis dataset comprised 1,666,716 men and women from 32 countries (63 cohorts), followed for a total of 16.0 million person-years. 292,785 had femoral neck BMD measured, from 52 cohorts in 20 countries, with a total follow-up time of 2.2 million person-years. We used an extended Poisson model in each cohort to investigate relationships between WHO-defined BMI categories (Underweight: <18.5kg/m2; Normal: 18.5-24.9kg/m2; Overweight: 25.0-29.9kg/m2; Obese I: 30.0-34.9kg/m2; Obese II: =35.0kg/m2) and risk of incident fracture, here presented for hip fracture (HF). Age, sex, BMD and duration of follow-up were considered as covariates. The inverse-variance weighted B -coefficients were used to merge the results from the individual cohorts. For the subset with BMD available, in models adjusted for age and time since baseline, lower BMI was associated with a greater risk of incident hip fracture in both sexes. Comparing underweight individuals with normal weight, the hazard ratio (95% CI) for HF was 2.35 (2.10-2.60) in women and for men was 2.45 (1.90-3.17). In both sexes, HF 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). Associations were not materially different to those in the whole cohort and were consistent for other fracture types. Further adjustment for femoral neck 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 inverted in the Obese II category [Obese II vs Normal: women 1.24 (0.97-1.58); men 1.70 (1.06-2.75)]. These findings, which will inform the next version of FRAX, demonstrate that underweight is a risk factor for fracture in both men and women regardless of adjustment for BMD. However, whilst overweight and obesity appeared protective in age- and follow-up time adjusted models, they became risk factors after additional adjustment for femoral neck BMD, particularly in the Obese II category. This effect in the highest BMI categories appeared of greater magnitude in men than women.