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

Eugene V. McCloskey; Helena Johansson; 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; Dan Mellström; Fiona E. A. McGuigan; 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; Marian Schini; Liesbeth Vandenput; Nicholas C. Harvey; Mattias Lorentzon; William D. Leslie; John A. Kanis

doi:10.1007/s00198-025-07607-w

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

Eugene V. McCloskey^*
, Helena Johansson
, 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, Dan Mellström, Fiona E. A. McGuigan, 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, Marian Schini, Liesbeth Vandenput, Nicholas C. Harvey, Mattias Lorentzon, William D. Leslie, John A. Kanis

^*Corresponding author for this work

University of Sheffield
Flinders University
Lund University
University of Massachusetts Medical School
Autonomous University of Barcelona
Generalitat de Catalunya
Cerdanyola del Vallès
PRECIOSA-Fundación Para La Investigación
Nordic Bioscience AS
Universite de Namur
University of Zurich
University of Geneva
University of Liege
University of Pittsburgh
Garvan Institute of Medical Research
University of New South Wales
Universite Claude Bernard Lyon 1
MRC Lifecourse Epidemiology Unit
NIHR Southampton Biomedical Research Centre
University of Oxford
University of California at Los Angeles
California Pacific Medical Center
University of Coimbra
Tufts University
Marcus Institute for Aging Research
Harvard University
University of Notre Dame Australia
Amsterdam UMC
Kansai Medical University
Yasuda Women's University
Universitätsklinikum Schleswig-Holstein Campus Kiel
Maccabi Healthcare Services
Tel Aviv University
McGill University
Icelandic Heart Association
University of Iceland
University of Edinburgh
University of Lausanne
Norwegian University of Science and Technology
University of Aberdeen
Vrije Universiteit Amsterdam
Kindai University
Elisha Hospital
University of Tasmania
Mayo Clinic Rochester, MN
National University of Singapore
Agency for Science, Technology and Research, Singapore
Erasmus University Rotterdam
Deakin University
Barwon Health
University of Melbourne
University of Eastern Finland
Chinese University of Hong Kong
Nord-Trøndelag Hospital Trust
Tehran University of Medical Sciences
University of Bern
University of Gothenburg
Sahlgrenska University Hospital
University of Technology Sydney
Tam Anh Hospital
Uppsala University
University of Tromsø – The Arctic University of Norway
University of Manchester
Medical University of Graz
Oregon Health and Science University
Monash University
National Institutes of Health
Janus Rehabilitation
National Institute on Aging Intramural Research Program
Université de Lyon
PHARMO Institute, Utrecht
Osaka Medical and Pharmaceutical University
University of York
Hospital del Mar
MRC Epidemiology Unit Insitute of Meatabolic Science University of Cambridge
Tulane University
The University of Tokyo
University of Girona
Institut Universitari d'Investigació en Atenció Primària Jordi Gol (IDIAP Jordi Gol)
University of Manitoba

Research output: Contribution to journal › Article › Academic › peer-review

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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.

Original language	English
Pages (from-to)	1725-1741
Number of pages	17
Journal	Osteoporosis international
Volume	36
Issue number	9
Early online date	2025
DOIs	https://doi.org/10.1007/s00198-025-07607-w
Publication status	Published - Sept 2025

Keywords

FRAX
Family history
Hip fracture
Meta-analysis
Osteoporotic fractureF
Parental history

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McCloskey, E. V., Johansson, H., 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., da Silva, J. A. P., ... Kanis, J. A. (2025). Family history of fracture and fracture risk: a meta-analysis to update the FRAX® risk assessment tool. Osteoporosis international, 36(9), 1725-1741. https://doi.org/10.1007/s00198-025-07607-w

@article{b8a07fac21b7457db465d54602e9fb95,

title = "Family history of fracture and fracture risk: a meta-analysis to update the FRAX{\textregistered} 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.",

keywords = "FRAX, Family history, Hip fracture, Meta-analysis, Osteoporotic fractureF, Parental history",

author = "McCloskey, \{Eugene V.\} and Helena Johansson 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 Dan Mellstr{\"o}m and McGuigan, \{Fiona E. A.\} and Thomas Merlijn and Nguyen, \{Tuan V.\} and Anna Nordstr{\"o}m and Peter Nordstr{\"o}m and O´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 Marian Schini and Liesbeth Vandenput and Harvey, \{Nicholas C.\} and Mattias Lorentzon and Leslie, \{William D.\} and Kanis, \{John A.\}",

note = "Publisher Copyright: {\textcopyright} The Author(s), under exclusive licence to the International Osteoporosis Foundation and the Bone Health and Osteoporosis Foundation 2025.",

year = "2025",

month = sep,

doi = "10.1007/s00198-025-07607-w",

language = "English",

volume = "36",

pages = "1725--1741",

journal = "Osteoporosis international",

issn = "0937-941X",

publisher = "Springer London",

number = "9",

}

McCloskey, EV, Johansson, H, 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, Mellström, D, McGuigan, FEA, 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, Schini, M, Vandenput, L, Harvey, NC, Lorentzon, M, Leslie, WD & Kanis, JA 2025, 'Family history of fracture and fracture risk: a meta-analysis to update the FRAX® risk assessment tool', Osteoporosis international, vol. 36, no. 9, pp. 1725-1741. https://doi.org/10.1007/s00198-025-07607-w

TY - JOUR

T1 - Family history of fracture and fracture risk

T2 - a meta-analysis to update the FRAX® risk assessment tool

AU - McCloskey, Eugene V.

AU - Johansson, Helena

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 - Mellström, Dan

AU - McGuigan, Fiona E. A.

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 - Schini, Marian

AU - Vandenput, Liesbeth

AU - Harvey, Nicholas C.

AU - Lorentzon, Mattias

AU - Leslie, William D.

AU - Kanis, John A.

N1 - Publisher Copyright: © The Author(s), under exclusive licence to the International Osteoporosis Foundation and the Bone Health and Osteoporosis Foundation 2025.

PY - 2025/9

Y1 - 2025/9

N2 - 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.

AB - 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.

KW - FRAX

KW - Family history

KW - Hip fracture

KW - Meta-analysis

KW - Osteoporotic fractureF

KW - Parental history

UR - https://www.scopus.com/pages/publications/105014188202

U2 - 10.1007/s00198-025-07607-w

DO - 10.1007/s00198-025-07607-w

M3 - Article

C2 - 40848065

SN - 0937-941X

VL - 36

SP - 1725

EP - 1741

JO - Osteoporosis international

JF - Osteoporosis international

IS - 9

ER -

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

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