McCloskey Eugene V, Johansson Helena, Liu Enwu, Åkesson Kristina E, Anderson Fred A, Azagra-Ledesma Rafael, Bager Cecilie L, Beaudart Charlotte, Bischoff-Ferrari Heike A, Biver Emmanuel, Bruyère Olivier, Cauley Jane A, Center Jacqueline R, Chapurlat Roland, Christiansen Claus, Cooper Cyrus, Crandall Carolyn J, Cummings Steven R, da Silva José A P, Dawson-Hughes Bess, Diez-Perez Adolfo, Dufour Alyssa B, Eisman John A, Elders Petra J M, Ferrari Serge, Fujita Yuki, Fujiwara Saeko, Glüer Claus-Christian, Goldshtein Inbal, Goltzman David, Gudnason Vilmundur, Hall Jill, Hans Didier, Hoff Mari, Hollick Rosemary J, Huisman Martijn, Iki Masayuki, Ish-Shalom Sophia, Jones Graeme, Karlsson Magnus K, Khosla Sundeep, Kiel Douglas P, Koh Woon-Puay, Koromani Fjorda, Kotowicz Mark A, Kröger Heikki, Kwok Timothy, Lamy Olivier, Langhammer Arnulf, Larijani Bagher, Lippuner Kurt, Mellström Dan, McGuigan Fiona E A, Merlijn Thomas, Nguyen Tuan V, Nordström Anna, Nordström Peter, O Neill Terence W, Obermayer-Pietsch Barbara, Ohlsson Claes, Orwoll Eric S, Pasco Julie A, Rivadeneira Fernando, Schei Berit, Schott Anne-Marie, Shiroma Eric J, Siggeirsdottir Kristin, Simonsick Eleanor M, Sornay-Rendu Elisabeth, Sund Reijo, Swart Karin M A, Szulc Pawel, Tamaki Junko, Torgerson David J, van Schoor Natasja M, van Staa Tjeerd P, Vila Joan, Wareham Nicholas J, Wright Nicole C, Yoshimura Noriko, Zillikens M Carola, Zwart Marta, Schini Marian, Vandenput Liesbeth, Harvey Nicholas C, Lorentzon Mattias, Leslie William D, Kanis John A
Centre for Metabolic Bone Diseases, University of Sheffield, Sheffield, UK.
Centre for Integrated Research in Musculoskeletal Ageing, Mellanby Centre for Musculoskeletal Research, Division of Clinical Medicine, School of Medicine & Population Health, University of Sheffield Medical School, Sheffield, UK.
Osteoporos Int. 2025 Aug 23. doi: 10.1007/s00198-025-07607-w.
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.
We have undertaken a meta-analysis of international prospective cohorts to quantify the relationship between a family history of fracture and future fracture incidence.
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.
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.
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.
在迄今为止最大规模的国际队列荟萃分析中，骨折家族史被确认为未来骨折风险的一个重要的、与骨密度无关的预测因素。父母和兄弟姐妹的骨折史对未来骨折具有同样的重要性，包括家族髋部骨折对未来髋部骨折风险的影响。
我们对国际前瞻性队列进行了荟萃分析，以量化骨折家族史与未来骨折发生率之间的关系。
分析数据集包括来自29个国家42个队列的350,542名男性和女性，随访时间达280万人年。我们在每个队列中使用扩展泊松模型研究髋部骨折或任何骨折的家族史与任何临床骨折、任何骨质疏松性骨折、主要骨质疏松性骨折（MOF）以及单独髋部骨折风险之间的关系。模型对当前年龄、性别、骨密度和随访时间进行了调整。
由于未发现骨折家族史对男女的影响存在差异，因此给出了男女合并的结果。父母有髋部骨折史与所有骨折结局类别中骨折发生风险较高相关，与未来髋部骨折的关系更强（髋部骨折和MOF的风险比（HR，95%CI）分别为1.37，1.23 - 1.52和1.19，1.12 - 1.27）。在额外调整骨密度后，关联略有降低但仍显著，且不因基线后代年龄、随访时间或受影响的父母而有所不同。在一项更有限的分析中，父母有任何骨折史或兄弟姐妹有髋部或任何骨折史与父母有髋部骨折史所观察到的关联相似。
骨折家族史被确认为未来骨折风险的一个重要的、与骨密度无关的预测因素。虽然父母髋部骨折似乎是未来髋部骨折的最强因素，但其他骨折的家族史可能适合纳入FRAX工具的未来版本中。
