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

Abstract

Summary

In the largest meta-analysis of international cohorts to date, a family history of fracture is confirmed as a significant BMD-independent predictor of future fracture risk. Parental and sibling histories of fracture carry the same significance for future fracture, including the impact of family hip fracture on future hip fracture risk.

Purpose

We have undertaken a meta-analysis of international prospective cohorts to quantify the relationship between a family history of fracture and future fracture incidence.

Methods

The analysis dataset comprised 350,542 men and women from 42 cohorts in 29 countries followed for 2.8 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.

Results

As no difference in influence of family history of fracture was seen between genders, results are presented for men and women combined. A parental history of hip fracture was associated with a higher risk of incident fracture across all fracture outcome categories, with a stronger relationship with future hip fracture (hazard ratios (HR, 95% CI) for hip and MOF 1.37, 1.23–1.52 and 1.19, 1.12–1.27, respectively). Associations were slightly reduced but remained significant when additionally adjusted for BMD and did not vary by baseline offspring age, follow-up time, or parent affected. In a more limited analysis, parental history of any fracture or a sibling history of hip or any fracture showed similar associations to those observed with parental history of hip fracture.

Conclusions

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, a family history of other fractures might be appropriate for inclusion in future iterations of the FRAX tool.

Metadata

Item Type:	Article
Authors/Creators:	McCloskey, E.V. https://orcid.org/0000-0003-0177-8140 Johansson, H. Liu, E. Åkesson, K.E. Anderson, F.A. Azagra-Ledesma, R. https://orcid.org/0000-0003-0093-333X Bager, C.L. Beaudart, C. Bischoff-Ferrari, H.A. Biver, E. https://orcid.org/0000-0001-6174-1951 Bruyère, O. https://orcid.org/0000-0003-4269-9393 Cauley, J.A. https://orcid.org/0000-0003-0752-4408 Center, J.R. https://orcid.org/0000-0002-5278-4527 Chapurlat, R. Christiansen, C. Cooper, C. Crandall, C.J. Cummings, S.R. da Silva, J.A.P. https://orcid.org/0000-0002-2782-6780 Dawson-Hughes, B. https://orcid.org/0000-0003-3136-0386 Diez-Perez, A. Dufour, A.B. Eisman, J.A. Elders, P.J.M. Ferrari, S. Fujita, Y. Fujiwara, S. Glüer, C.-C. Goldshtein, I. Goltzman, D. Gudnason, V. Hall, J. Hans, D. https://orcid.org/0000-0003-1826-5958 Hoff, M. https://orcid.org/0000-0002-9992-8663 Hollick, R.J. Huisman, M. Iki, M. https://orcid.org/0000-0003-2128-5255 Ish-Shalom, S. Jones, G. Karlsson, M.K. Khosla, S. Kiel, D.P. Koh, W.-P. Koromani, F. Kotowicz, M.A. https://orcid.org/0000-0002-8094-1411 Kröger, H. https://orcid.org/0000-0003-4245-8186 Kwok, T. Lamy, O. Langhammer, A. https://orcid.org/0000-0001-5296-6673 Larijani, B. https://orcid.org/0009-0007-9526-9430 Lippuner, K. Mellström, D. McGuigan, F.E.A. Merlijn, T. Nguyen, T.V. https://orcid.org/0000-0002-3246-6281 Nordström, A. Nordström, P. https://orcid.org/0000-0003-2924-508X O´Neill, T.W. Obermayer-Pietsch, B. https://orcid.org/0000-0003-3543-1807 Ohlsson, C. Orwoll, E.S. https://orcid.org/0000-0002-8520-7355 Pasco, J.A. https://orcid.org/0000-0002-8968-4714 Rivadeneira, F. Schei, B. Schott, A.-M. https://orcid.org/0000-0003-3337-4474 Shiroma, E.J. Siggeirsdottir, K. https://orcid.org/0000-0002-4643-8732 Simonsick, E.M. https://orcid.org/0000-0002-5460-3494 Sornay-Rendu, E. Sund, R. https://orcid.org/0000-0002-6268-8117 Swart, K.M.A. Szulc, P. Tamaki, J. Torgerson, D.J. van Schoor, N.M. van Staa, T.P. https://orcid.org/0000-0001-9363-742X Vila, J. Wareham, N.J. Wright, N.C. Yoshimura, N. https://orcid.org/0000-0001-9206-4658 Zillikens, M.C. https://orcid.org/0000-0001-9186-3423 Zwart, M. https://orcid.org/0000-0003-4888-0927 Schini, M. https://orcid.org/0000-0003-2204-2095 Vandenput, L. Harvey, N.C. Lorentzon, M. Leslie, W.D. https://orcid.org/0000-0002-1056-1691 Kanis, J.A.
Copyright, Publisher and Additional Information:	© 2025 The Authors. Except as otherwise noted, this author-accepted version of a journal article published in Osteoporosis International is made available via the University of Sheffield Research Publications and Copyright Policy under the terms of the Creative Commons Attribution 4.0 International License (CC-BY 4.0), which permits unrestricted use, distribution and reproduction in any medium, provided the original work is properly cited. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/
Keywords:	FRAX; Family history; Hip fracture; Meta-analysis; Osteoporotic fractureF; Parental history
Dates:	Accepted: 15 June 2025 Published (online): 23 August 2025 Published: 23 August 2025
Institution:	The University of Sheffield
Academic Units:	The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > School of Medicine and Population Health
Depositing User:	Symplectic Sheffield
Date Deposited:	04 Sep 2025 15:46
Last Modified:	04 Sep 2025 20:38
Status:	Published online
Publisher:	Springer Science and Business Media LLC
Refereed:	Yes
Identification Number:	10.1007/s00198-025-07607-w
Related URLs:	PubMed URL
Open Archives Initiative ID (OAI ID):	oai:eprints.whiterose.ac.uk:231241

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

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