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ARS Home » Northeast Area » Boston, Massachusetts » Jean Mayer Human Nutrition Research Center On Aging » Research » Publications at this Location » Publication #428968
Research Project: Diet Quality and Physical Activity for Healthy Aging and Chronic Disease Mitigation

Location: Jean Mayer Human Nutrition Research Center On Aging

Title: Family history of fracture and fracture risk: a meta-analysis to update the FRAX risk assessment tool

Author
item MCCLOSKEY, EUGENE - University Of Sheffield Medical School
item JOHANSSON, HELENA - University Of Gothenburg
item LIU, ENWU - Australian Catholic University
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 BISCHOFF-FERRARI, HEIKE - University Of Zurich
item BIVER, EMMANUEL - University Of Geneva
item BRUYERE, OLIVER - 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
item CUMMINGS, STEVEN - California Pacific Medical Center Research Institute
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 FERRAIR, SERGE - University Of Geneva
item FUJITA, YUKI - Kansai Research Center
item FUJIWARA, SAEKO - Yasuda Women'S University
item GLUER, CLAUS CHRISTIAN - Christian Albrechts University - Kiel University
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, MARIE - Norwegian University Of Science And Technology
item HOLLICK, ROSEMARY - University Of Aberdeen
item HUISMAN, MARTIJN - Vu University Medical Center
item IKI, MASAYUKI - Kindai University
item ISH SHALOM, SOPHIA - Elisha Hospital
item JONES, GRAEME - University Of Tasmania
item KARLSSON, MAGNUS - Lund University
item KHOSLA, DUNDEEP - Mayo Clinic
item KIEL, DOUGLAS - Marcus Institute For Aging Research
item KOH, WOON PUA - National University Of Singapore
item KOROMANI, FJORDA - Erasmus University
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 LIPPUNER, KURT - University Of Bern
item MELLSTROM, DAN - University Of Gothenburg
item MERLJIN, THOMAS - Amsterdam Public Health Research Institute
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 University
item SCHEI, BERIT - Norwegian University Of Science And Technology
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 - Institut National De La Sante Et De La Recherche Medicale (INSERM)
item TAMAKI, JUNKO - Educational Foundation Of Osaka Medical And Pharmaceutical University
item TORGERSON, DAVID - University Of York
item VAN SCHOOR, NATASJA - University Medical Center Amsterdam
item VAN STAA, TJEERD - University Of Manchester
item VILA, JOAN - Hospital Del Mar Medical Research Institute
item WAREHAM, NICHOLAS - University Of Cambridge
item WRIGHT, NICOLE - University Of Alabama At Birmingham
item YOSHIMURA, NORIKO - University Of Tokyo
item ZILLIKENS, M. CAROLA - Erasmus University
item ZWART, MARTA - Institut Universitari D'Investigacio En Atencio Primaria Jordi Gol
item SCHINI, MARIAN - University Of Sheffield
item VANDENPUT, LIESBETH - University Of Gothenburg
item HARVEY, NICHOLAS - University Of Southampton
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: 6/15/2025
Publication Date: 8/24/2025
Citation: Mccloskey, E., Johansson, H., Liu, E., Akesson, K., Anderson, F.A., Azagra, R., Bager, C., Beaudart, C., Bischoff-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., Eisman, J., Elders, P., Ferrair, S., Fujita, Y., Fujiwara, S., Gluer, C., Goldshtein, I., Goltzman, D., Gudnason, V., Hall, J., Hans, D., Hoff, M., Hollick, R., Huisman, M., Iki, M., Ish Shalom, S., Jones, G., Karlsson, M.K., Khosla, D., Kiel, D.P., Koh, W., Koromani, F., Kotowicz, M., Kroger, H., Kwok, T., Lamy, O., Langhammer, A., Larijani, B., Lippuner, K., Mellstrom, D., Merljin, T., Nordstrom, A., Nordstrom, P., O'Neill, T., Obermayer-Pietsch, B., Ohlsson, C., Orwoll, E., Pasco, J.A., Rivadeneira, F., Schei, B., 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., Vila, J., Wareham, N.J., Wright, N.C., Yoshimura, N., Zillikens, M., Zwart, M., Schini, M., Vandenput, L., Harvey, N.C., Lorentzon, M., Leslie, W.D., Kanis, J.A. 2025. Family history of fracture and fracture risk: a meta-analysis to update the FRAX risk assessment tool . Osteoporosis International. https://doi.org/10.1007/s00198-025-07607-w.
DOI: https://doi.org/10.1007/s00198-025-07607-w

Interpretive Summary: This analysis was undertaken to quantify the relationship between a family history of fracture and future fracture risk. This information will be used to update the widely used FRAX fracture risk calculator. The analysis dataset is comprised of 350,542 men and women from 42 cohorts, including the Boston STOP IT trial, in 29 countries. We investigated the relationship between family history of hip fracture or any fracture and the risk of any future fracture. No difference in the influence of family history of fracture was seen between the sexes and results are presented for men and women combined. A family history of hip fracture was associated with higher risk of incident fracture overall, and the association was strongest for incident hip fractures such that a family history of a hip fracture raised risk of hip fracture by 37%. In this large international cohort meta-analysis, a family history of fracture is confirmed as a significant predictor of future fracture risk and parental hip fracture appears the strongest factor for future hip fracture. The findings also suggest that a family history of other fractures might be appropriate for inclusion in future iterations of the FRAX tool.

Technical Abstract: We have undertaken a meta-analysis of international prospective cohorts to quantify the relationship between a family history of fracture and future fracture incidence, when adjusted for age, sex, time since baseline and femoral neck bone mineral density (BMD). The analysis dataset comprised 350,542 men and women from 42 cohorts in 29 countries followed for a total of 2.78 million person-years. We investigated the relationship between family history of hip fracture or any fracture and the risk of any clinical fracture, any osteoporotic fracture, major osteoporotic fracture (MOF) and hip fracture alone using an extended Poisson model in each cohort. Models were adjusted for current age, sex, BMD, and follow up time. The results of the different studies were merged using inverse weighted B-coefficients. We evaluated if the association between family fracture history differed by age, follow-up time, and family member affected (maternal, paternal or sibling) using traditional interaction terms. After adjustment for age and time since baseline, no difference in the influence of family history of fracture was seen between the sexes and results are presented for men and women combined. A family history of hip fracture was associated with higher risk of incident fracture across all of the fracture outcome categories in both men and women. For example, the hazard ratios [HR, 95%CI] for MOF and osteoporotic fracture were similar (1.19, 1.12-1.27 and 1.16, 1.10-1.23 respectively). The association was strongest for incident hip fractures alone [HR 1.37, 1.23-1.52). Associations were slightly reduced but remained significant when additionally adjusted for BMD; they did not vary by age, follow-up time or family member affected. In a more limited analysis of parental history of any fracture or a sibling history of hip or any fracture, similar associations to those observed with parental history of hip fracture were observed. In this large international cohort meta-analysis, a family history of fracture is confirmed as a significant BMD-independent predictor of future fracture risk. While parental hip fracture appears the strongest factor for future hip fracture, the findings also suggest that a family history of other fractures might be appropriate for inclusion in future iterations of the FRAX tool.