Family history of fracture and fracture risk: a meta-analysis to update the FRAX® risk assessment tool
Eugène McCloskey, Helena Johansson, Enwu Liu, Kristina Åkesson, Fred Anderson, Rafael Azagra, Cecilie L. Bager, Charlotte Beaudart, Heike A. Bischoff‐Ferrari, Emmanuel Biver, Olivier Bruyère, Jane A. Cauley, Roland Chapurlat, Claus Christiansen, Cyrus Cooper, Carolyn Crandall, Steven R. Cummings, José António Pereira da Silva, Bess Dawson‐Hughes, Adolfo Díez‐Pérez, Alyssa B. Dufour, John A. Eisman, Petra J. M. Elders, Serge Ferrari, Yuki Fujita, Saeko Fujiwara, Claus‐Christian Glüer, Inbal Goldshtein, David Goltzman, Vilmundur Guðnason, Jill Hall, Didier Hans, Mari Hoff, Rosemary 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. McGuigan, Thomas Merlijn, Tuan V. Nguyen, Anna Nordström, Peter Nordström, Terence W O’Neill, Barbara Obermayer‐Pietsch, Claes Ohlsson, Eric Orwoll, Julie A. Pasco, Fernando Rivadeneira, Berit Schei, Anne‐Marie Schott, Eric J. Shiroma, Kristín Siggeirsdóttir, Eleanor M. Simonsick, Elisabeth Sornay‐Rendu, Reijo Sund, Karin M. A. Swart, Paweł Szulc, Junko Tamaki, David Torgerson, Natasja M. van Schoor, Tjeerd 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 А. Kanis
Abstract
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.