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

Eugene V McCloskey^{1

2}, Helena Johansson³, Enwu Liu⁴, Kristina E Åkesson^{5

6}, Fred A Anderson⁷, Rafael Azagra-Ledesma^{8

9

10

11}, Cecilie L Bager¹², Charlotte Beaudart¹³, Heike A Bischoff-Ferrari^{14

15}, Emmanuel Biver¹⁶, Olivier Bruyère¹⁷, Jane A Cauley¹⁸, Jacqueline R Center^{19

20}, Roland Chapurlat²¹, Claus Christiansen¹², Cyrus Cooper^{22

23

24}, Carolyn J Crandall²⁵, Steven R Cummings²⁶, José A P da Silva^{27

28}, Bess Dawson-Hughes²⁹, Adolfo Diez-Perez³⁰, Alyssa B Dufour^{31

32}, John A Eisman^{20

33

34}, Petra J M Elders³⁵, Serge Ferrari¹⁶, Yuki Fujita³⁶, Saeko Fujiwara³⁷, Claus-Christian Glüer³⁸, Inbal Goldshtein^{39

40}, David Goltzman⁴¹, Vilmundur Gudnason^{42

43}, Jill Hall⁴⁴, Didier Hans⁴⁵, Mari Hoff^{46

47}, Rosemary J Hollick⁴⁸, Martijn Huisman^{49

50}, Masayuki Iki⁵¹, Sophia Ish-Shalom⁵², Graeme Jones⁵³, Magnus K Karlsson^{5

54}, Sundeep Khosla⁵⁵, Douglas P Kiel^{31

32}, Woon-Puay Koh^{56

57}, Fjorda Koromani^{58

59}, Mark A Kotowicz^{60

61

62}, Heikki Kröger^{63

64}, Timothy Kwok^{65

66}, Olivier Lamy^{67

68}, Arnulf Langhammer^{69

70}, Bagher Larijani⁷¹, Kurt Lippuner⁷², Dan Mellström^{73

74}, Fiona E A McGuigan⁵, Thomas Merlijn³⁵, Tuan V Nguyen^{75

76

77}, Anna Nordström^{78

79}, Peter Nordström⁸⁰, Terence W O Neill⁸¹, Barbara Obermayer-Pietsch⁸², Claes Ohlsson^{83

84}, Eric S Orwoll⁸⁵, Julie A Pasco^{60

61

62

86}, Fernando Rivadeneira⁵⁸, Berit Schei^{87

88}, Anne-Marie Schott⁸⁹, Eric J Shiroma⁹⁰, Kristin Siggeirsdottir^{42

91}, Eleanor M Simonsick⁹², Elisabeth Sornay-Rendu⁹³, Reijo Sund⁶⁴, Karin M A Swart^{94

95}, Pawel Szulc⁹³, Junko Tamaki⁹⁶, David J Torgerson⁹⁷, Natasja M van Schoor⁴⁹, Tjeerd P van Staa⁹⁸, Joan Vila⁹⁹, Nicholas J Wareham¹⁰⁰, Nicole C Wright¹⁰¹, Noriko Yoshimura¹⁰², M Carola Zillikens⁵⁸, Marta Zwart^{103

104

105}, Marian Schini¹⁰⁶, Liesbeth Vandenput⁸³, Nicholas C Harvey^{22

23}, Mattias Lorentzon^{107

108}, William D Leslie¹⁰⁹, John A Kanis³

Affiliations

¹ Centre for Metabolic Bone Diseases, University of Sheffield, Sheffield, UK. e.v.mccloskey@sheffield.ac.uk.
² 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. e.v.mccloskey@sheffield.ac.uk.
³ Centre for Metabolic Bone Diseases, University of Sheffield, Sheffield, UK.
⁴ College of Medicine and Public Health, Flinders University, Adelaide, Australia.
⁵ Clinical and Molecular Osteoporosis Research Unit, Department of Clinical Sciences, Lund University, Lund, Sweden.
⁶ Department of Orthopedics, Skåne University Hospital, Malmö, Sweden.
⁷ GLOW Coordinating Center, Center for Outcomes Research, University of Massachusetts Medical School, Worcester, MA, USA.
⁸ Department of Medicine, Autonomous University of Barcelona, Barcelona, Spain.
⁹ Health Centre Badia del Valles, Catalan Institute of Health, Barcelona, Spain.
¹⁰ GROIMAP (Research Group), Unitat de Suport a La Recerca Metropolitana Nord, Institut Universitari d'Investigació en Atenció Primària Jordi Gol, Cerdanyola del Vallès, Barcelona, Spain.
¹¹ PRECIOSA-Fundación Para La Investigación, Barberà del Vallés, Barcelona, Spain.
¹² Nordic Bioscience A/S, Herlev, Denmark.
¹³ Public Health Aging Research & Epidemiology (PHARE) Group, Research Unit in Clinical Pharmacology and Toxicology (URPC), NAmur Research Institute for LIfe Sciences (NARILIS), University of Namur, Namur, Belgium.
¹⁴ Department of Aging Medicine and Aging Research, University Hospital, Zurich, and University of Zurich, Zurich, Switzerland.
¹⁵ Centre On Aging and Mobility, University of Zurich and City Hospital, Zurich, Switzerland.
¹⁶ Division of Bone Diseases, Department of Medicine, Geneva University Hospitals and Faculty of Medicine, University of Geneva, Geneva, Switzerland.
¹⁷ Research Unit in Public Health, Epidemiology and Health Economics, University of Liège, Liège, Belgium.
¹⁸ Department of Epidemiology, School of Public Health, University of Pittsburgh, Pittsburgh, Philadelphia, USA.
¹⁹ Garvan Institute of Medical Research, Sydney, NSW, Australia.
²⁰ St Vincent's Clinical School, School of Medicine and Health, University of New South Wales Sydney, Sydney, NSW, Australia.
²¹ INSERM UMR 1033, Université Claude Bernard-Lyon1, Hôpital Edouard Herriot, Lyon, France.
²² MRC Lifecourse Epidemiology Centre, University of Southampton, Southampton, UK.
²³ NIHR Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, UK.
²⁴ NIHR Oxford Biomedical Research Unit, University of Oxford, Oxford, UK.
²⁵ Division of General Internal Medicine and Health Services Research, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
²⁶ San Francisco Coordinating Center, California Pacific Medical Center Research Institute, San Francisco, CA, USA.
²⁷ Coimbra Institute for Clinical and Biomedical Research, Faculty of Medicine, University of Coimbra, Coimbra, Portugal.
²⁸ Rheumatology Department, University Hospital and University of Coimbra, Coimbra, Portugal.
²⁹ Bone Metabolism Laboratory, Jean Mayer US Department of Agriculture Human Nutrition Research Center On Aging, Tufts University, Boston, MA, USA.
³⁰ Department of Internal Medicine, Hospital del Mar and CIBERFES, Autonomous University of Barcelona, Barcelona, Spain.
³¹ Marcus Institute for Aging Research, Hebrew SeniorLife, Boston, MA, USA.
³² Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
³³ Skeletal Diseases Program, Garvan Institute of Medical Research, Sydney, NSW, Australia.
³⁴ School of Medicine Sydney, University of Notre Dame Australia, Sydney, NSW, Australia.
³⁵ Department of General Practice, Amsterdam UMC, Location AMC, Amsterdam Public Health Research Institute, Amsterdam, The Netherlands.
³⁶ Department of Hygiene and Public Health, Faculty of Medicine, Kansai Medical University, Osaka, Japan.
³⁷ Department of Pharmacy, Yasuda Women's University, Hiroshima, Japan.
³⁸ Section Biomedical Imaging, Molecular Imaging North Competence Center, Department of Radiology and Neuroradiology, University Medical Center Schleswig-Holstein Kiel, Kiel University, Kiel, Germany.
³⁹ Maccabitech Institute of Research and Innovation, Maccabi Healthcare Services, Tel Aviv, Israel.
⁴⁰ Department of Epidemiology and Preventive Medicine, School of Public Health, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
⁴¹ Department of Medicine, McGill University and McGill University Health Centre, Montreal, Canada.
⁴² Icelandic Heart Association, Kopavogur, Iceland.
⁴³ University of Iceland, Reykjavik, Iceland.
⁴⁴ MRC Centre for Reproductive Health, University of Edinburgh, Edinburgh, UK.
⁴⁵ Centre of Bone Diseases, Bone and Joint Department, Lausanne University Hospital, Lausanne, Switzerland.
⁴⁶ Department of Neuromedicine and Movement Science, Norwegian University of Science and Technology, Trondheim, Norway.
⁴⁷ Department of Rheumatology, St Olavs Hospital, Trondheim, Norway.
⁴⁸ Aberdeen Centre for Arthritis and Musculoskeletal Health, Epidemiology Group, University of Aberdeen, Aberdeen, UK.
⁴⁹ Department of Epidemiology and Data Science, Amsterdam Public Health Research Institute, VU University Medical Center, Amsterdam, The Netherlands.
⁵⁰ Department of Sociology, VU University, Amsterdam, The Netherlands.
⁵¹ Department of Public Health, Faculty of Medicine, Kindai University, Osaka, Japan.
⁵² Endocrine Clinic, Elisha Hospital, Haifa, Israel.
⁵³ Menzies Institute for Medical Research, University of Tasmania, Hobart, Australia.
⁵⁴ Department of Orthopaedics, Skåne University Hospital, Malmö, Sweden.
⁵⁵ Robert and Arlene Kogod Center On Aging and Division of Endocrinology, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, MN, USA.
⁵⁶ Healthy Longevity Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
⁵⁷ A*STAR Institute for Human Development and Potential, Singapore, Singapore.
⁵⁸ Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands.
⁵⁹ Department of Radiology and Nuclear Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands.
⁶⁰ IMPACT (Institute for Mental and Physical Health and Clinical Translation), Deakin University, Geelong, VIC, Australia.
⁶¹ Barwon Health, Geelong, VIC, Australia.
⁶² Department of Medicine - Western Health, The University of Melbourne, St Albans, Victoria, Australia.
⁶³ Department of Orthopedics and Traumatology, Kuopio University Hospital, Kuopio, Finland.
⁶⁴ Kuopio Musculoskeletal Research Unit, University of Eastern Finland, Kuopio, Finland.
⁶⁵ Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, Hong Kong.
⁶⁶ Jockey Club Centre for Osteoporosis Care and Control, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, Hong Kong.
⁶⁷ Centre of Bone Diseases, Lausanne University Hospital, Lausanne, Switzerland.
⁶⁸ Service of Internal Medicine, Lausanne University Hospital, Lausanne, Switzerland.
⁶⁹ HUNT Research Centre, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Levanger, Norway.
⁷⁰ Levanger Hospital, Nord-Trøndelag Hospital Trust, Levanger, Norway.
⁷¹ Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
⁷² Faculty of Medicine, ARTORG Center for Biomedical Engineering Research, University of Bern, Bern, Switzerland.
⁷³ Geriatric Medicine, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
⁷⁴ Geriatric Medicine, Sahlgrenska University Hospital Mölndal, Mölndal, Sweden.
⁷⁵ School of Biomedical Engineering, University of Technology Sydney, Sydney, Australia.
⁷⁶ School of Population Health, UNSW Medicine, UNSW Sydney, Kensington, Australia.
⁷⁷ Tam Anh Research Institute, Tam Anh Hospital, Ho Chi Minh City, Vietnam.
⁷⁸ Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
⁷⁹ School of Sport Sciences, Arctic University of Norway, Tromsø, Norway.
⁸⁰ Department of Public Health and Caring Sciences, Clinical Geriatrics, Uppsala University, Uppsala, Sweden.
⁸¹ Caring Sciences, Clinical Geriatrics, Centre for Epidemiology Versus Arthritis, University of Manchester, Manchester, UK.
⁸² Div. of Endocrinology and Diabetology, Dept. of Internal Medicine, Medical University Graz, Endocrine Lab Platform, Auenbruggerplatz 15, 8036, Graz, Austria.
⁸³ Sahlgrenska Osteoporosis Centre, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
⁸⁴ Department of Drug Treatment, Sahlgrenska University Hospital, Region Västra Götaland, Gothenburg, Sweden.
⁸⁵ Department of Medicine, Oregon Health and Science University, Portland, OR, USA.
⁸⁶ Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia.
⁸⁷ Department of Public Health and Nursing, Norwegian University of Science and Technology, Trondheim, Norway.
⁸⁸ Department of Gynecology, St Olavs Hospital, Trondheim, Norway.
⁸⁹ Université Claude Bernard Lyon 1, U INSERM 1290 RESHAPE, Lyon, France.
⁹⁰ Laboratory of Epidemiology and Population Sciences, National Institute On Aging, Baltimore, MD, USA.
⁹¹ Janus Rehabilitation, Reykjavik, Iceland.
⁹² Translational Gerontology Branch, National Institute On Aging Intramural Research Program, Baltimore, MD, USA.
⁹³ UMR 1033, INSERM, University of Lyon, Hôpital Edouard Herriot, Lyon, France.
⁹⁴ Department of General Practice, Amsterdam Public Health Research Institute, Amsterdam UMC, Location VUmc, Amsterdam, The Netherlands.
⁹⁵ PHARMO Institute for Drug Outcomes Research, Utrecht, The Netherlands.
⁹⁶ Department of Hygiene and Public Health, Faculty of Medicine, Educational Foundation of Osaka Medical and Pharmaceutical University, Osaka, Japan.
⁹⁷ York Trials Unit, Department of Health Sciences, University of York, York, UK.
⁹⁸ Centre for Health Informatics, Faculty of Biology, Medicine and Health, School of Health Sciences, University of Manchester, Manchester, UK.
⁹⁹ Statistics Support Unit, Hospital del Mar Medical Research Institute, CIBER Epidemiology and Public Health (CIBERESP), Barcelona, Spain.
¹⁰⁰ MRC Epidemiology Unit, University of Cambridge, Cambridge, UK.
¹⁰¹ Center for Health Outcomes, Implementation, Community-Engaged Sciences, School of Medicine, Tulane University, New Orleans, LA, USA.
¹⁰² Department of Preventive Medicine for Locomotive Organ Disorders, 22Nd Century Medical and Research Center, The University of Tokyo, Tokyo, Japan.
¹⁰³ Health Center Can Gibert del Plà, Catalan Institute of Health, Girona, Spain.
¹⁰⁴ Department of Medical Sciences, University of Girona, Girona, Spain.
¹⁰⁵ GROICAP (Research Group), Institut Universitari d'Investigació en Atenció Primària Jordi Gol, Girona, Spain.
¹⁰⁶ 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.
¹⁰⁷ Sahlgrenska Osteoporosis Centre, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden.
¹⁰⁸ Geriatric Medicine, Region Västra Götaland, Sahlgrenska University Hospital, Gothenburg, Mölndal, Sweden.
¹⁰⁹ Department of Medicine, University of Manitoba, Winnipeg, MB, Canada.

PMID: 40848065
DOI: 10.1007/s00198-025-07607-w

Free article

Meta-Analysis

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

Eugene V McCloskey et al. Osteoporos Int. 2025 Sep.

Free article

. 2025 Sep;36(9):1725-1741.

doi: 10.1007/s00198-025-07607-w. Epub 2025 Aug 23.

Authors

Affiliations

¹ Centre for Metabolic Bone Diseases, University of Sheffield, Sheffield, UK. e.v.mccloskey@sheffield.ac.uk.
² 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. e.v.mccloskey@sheffield.ac.uk.
³ Centre for Metabolic Bone Diseases, University of Sheffield, Sheffield, UK.
⁴ College of Medicine and Public Health, Flinders University, Adelaide, Australia.
⁵ Clinical and Molecular Osteoporosis Research Unit, Department of Clinical Sciences, Lund University, Lund, Sweden.
⁶ Department of Orthopedics, Skåne University Hospital, Malmö, Sweden.
⁷ GLOW Coordinating Center, Center for Outcomes Research, University of Massachusetts Medical School, Worcester, MA, USA.
⁸ Department of Medicine, Autonomous University of Barcelona, Barcelona, Spain.
⁹ Health Centre Badia del Valles, Catalan Institute of Health, Barcelona, Spain.
¹⁰ GROIMAP (Research Group), Unitat de Suport a La Recerca Metropolitana Nord, Institut Universitari d'Investigació en Atenció Primària Jordi Gol, Cerdanyola del Vallès, Barcelona, Spain.
¹¹ PRECIOSA-Fundación Para La Investigación, Barberà del Vallés, Barcelona, Spain.
¹² Nordic Bioscience A/S, Herlev, Denmark.
¹³ Public Health Aging Research & Epidemiology (PHARE) Group, Research Unit in Clinical Pharmacology and Toxicology (URPC), NAmur Research Institute for LIfe Sciences (NARILIS), University of Namur, Namur, Belgium.
¹⁴ Department of Aging Medicine and Aging Research, University Hospital, Zurich, and University of Zurich, Zurich, Switzerland.
¹⁵ Centre On Aging and Mobility, University of Zurich and City Hospital, Zurich, Switzerland.
¹⁶ Division of Bone Diseases, Department of Medicine, Geneva University Hospitals and Faculty of Medicine, University of Geneva, Geneva, Switzerland.
¹⁷ Research Unit in Public Health, Epidemiology and Health Economics, University of Liège, Liège, Belgium.
¹⁸ Department of Epidemiology, School of Public Health, University of Pittsburgh, Pittsburgh, Philadelphia, USA.
¹⁹ Garvan Institute of Medical Research, Sydney, NSW, Australia.
²⁰ St Vincent's Clinical School, School of Medicine and Health, University of New South Wales Sydney, Sydney, NSW, Australia.
²¹ INSERM UMR 1033, Université Claude Bernard-Lyon1, Hôpital Edouard Herriot, Lyon, France.
²² MRC Lifecourse Epidemiology Centre, University of Southampton, Southampton, UK.
²³ NIHR Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, UK.
²⁴ NIHR Oxford Biomedical Research Unit, University of Oxford, Oxford, UK.
²⁵ Division of General Internal Medicine and Health Services Research, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
²⁶ San Francisco Coordinating Center, California Pacific Medical Center Research Institute, San Francisco, CA, USA.
²⁷ Coimbra Institute for Clinical and Biomedical Research, Faculty of Medicine, University of Coimbra, Coimbra, Portugal.
²⁸ Rheumatology Department, University Hospital and University of Coimbra, Coimbra, Portugal.
²⁹ Bone Metabolism Laboratory, Jean Mayer US Department of Agriculture Human Nutrition Research Center On Aging, Tufts University, Boston, MA, USA.
³⁰ Department of Internal Medicine, Hospital del Mar and CIBERFES, Autonomous University of Barcelona, Barcelona, Spain.
³¹ Marcus Institute for Aging Research, Hebrew SeniorLife, Boston, MA, USA.
³² Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
³³ Skeletal Diseases Program, Garvan Institute of Medical Research, Sydney, NSW, Australia.
³⁴ School of Medicine Sydney, University of Notre Dame Australia, Sydney, NSW, Australia.
³⁵ Department of General Practice, Amsterdam UMC, Location AMC, Amsterdam Public Health Research Institute, Amsterdam, The Netherlands.
³⁶ Department of Hygiene and Public Health, Faculty of Medicine, Kansai Medical University, Osaka, Japan.
³⁷ Department of Pharmacy, Yasuda Women's University, Hiroshima, Japan.
³⁸ Section Biomedical Imaging, Molecular Imaging North Competence Center, Department of Radiology and Neuroradiology, University Medical Center Schleswig-Holstein Kiel, Kiel University, Kiel, Germany.
³⁹ Maccabitech Institute of Research and Innovation, Maccabi Healthcare Services, Tel Aviv, Israel.
⁴⁰ Department of Epidemiology and Preventive Medicine, School of Public Health, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
⁴¹ Department of Medicine, McGill University and McGill University Health Centre, Montreal, Canada.
⁴² Icelandic Heart Association, Kopavogur, Iceland.
⁴³ University of Iceland, Reykjavik, Iceland.
⁴⁴ MRC Centre for Reproductive Health, University of Edinburgh, Edinburgh, UK.
⁴⁵ Centre of Bone Diseases, Bone and Joint Department, Lausanne University Hospital, Lausanne, Switzerland.
⁴⁶ Department of Neuromedicine and Movement Science, Norwegian University of Science and Technology, Trondheim, Norway.
⁴⁷ Department of Rheumatology, St Olavs Hospital, Trondheim, Norway.
⁴⁸ Aberdeen Centre for Arthritis and Musculoskeletal Health, Epidemiology Group, University of Aberdeen, Aberdeen, UK.
⁴⁹ Department of Epidemiology and Data Science, Amsterdam Public Health Research Institute, VU University Medical Center, Amsterdam, The Netherlands.
⁵⁰ Department of Sociology, VU University, Amsterdam, The Netherlands.
⁵¹ Department of Public Health, Faculty of Medicine, Kindai University, Osaka, Japan.
⁵² Endocrine Clinic, Elisha Hospital, Haifa, Israel.
⁵³ Menzies Institute for Medical Research, University of Tasmania, Hobart, Australia.
⁵⁴ Department of Orthopaedics, Skåne University Hospital, Malmö, Sweden.
⁵⁵ Robert and Arlene Kogod Center On Aging and Division of Endocrinology, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, MN, USA.
⁵⁶ Healthy Longevity Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
⁵⁷ A*STAR Institute for Human Development and Potential, Singapore, Singapore.
⁵⁸ Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands.
⁵⁹ Department of Radiology and Nuclear Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands.
⁶⁰ IMPACT (Institute for Mental and Physical Health and Clinical Translation), Deakin University, Geelong, VIC, Australia.
⁶¹ Barwon Health, Geelong, VIC, Australia.
⁶² Department of Medicine - Western Health, The University of Melbourne, St Albans, Victoria, Australia.
⁶³ Department of Orthopedics and Traumatology, Kuopio University Hospital, Kuopio, Finland.
⁶⁴ Kuopio Musculoskeletal Research Unit, University of Eastern Finland, Kuopio, Finland.
⁶⁵ Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, Hong Kong.
⁶⁶ Jockey Club Centre for Osteoporosis Care and Control, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, Hong Kong.
⁶⁷ Centre of Bone Diseases, Lausanne University Hospital, Lausanne, Switzerland.
⁶⁸ Service of Internal Medicine, Lausanne University Hospital, Lausanne, Switzerland.
⁶⁹ HUNT Research Centre, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Levanger, Norway.
⁷⁰ Levanger Hospital, Nord-Trøndelag Hospital Trust, Levanger, Norway.
⁷¹ Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
⁷² Faculty of Medicine, ARTORG Center for Biomedical Engineering Research, University of Bern, Bern, Switzerland.
⁷³ Geriatric Medicine, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
⁷⁴ Geriatric Medicine, Sahlgrenska University Hospital Mölndal, Mölndal, Sweden.
⁷⁵ School of Biomedical Engineering, University of Technology Sydney, Sydney, Australia.
⁷⁶ School of Population Health, UNSW Medicine, UNSW Sydney, Kensington, Australia.
⁷⁷ Tam Anh Research Institute, Tam Anh Hospital, Ho Chi Minh City, Vietnam.
⁷⁸ Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
⁷⁹ School of Sport Sciences, Arctic University of Norway, Tromsø, Norway.
⁸⁰ Department of Public Health and Caring Sciences, Clinical Geriatrics, Uppsala University, Uppsala, Sweden.
⁸¹ Caring Sciences, Clinical Geriatrics, Centre for Epidemiology Versus Arthritis, University of Manchester, Manchester, UK.
⁸² Div. of Endocrinology and Diabetology, Dept. of Internal Medicine, Medical University Graz, Endocrine Lab Platform, Auenbruggerplatz 15, 8036, Graz, Austria.
⁸³ Sahlgrenska Osteoporosis Centre, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
⁸⁴ Department of Drug Treatment, Sahlgrenska University Hospital, Region Västra Götaland, Gothenburg, Sweden.
⁸⁵ Department of Medicine, Oregon Health and Science University, Portland, OR, USA.
⁸⁶ Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia.
⁸⁷ Department of Public Health and Nursing, Norwegian University of Science and Technology, Trondheim, Norway.
⁸⁸ Department of Gynecology, St Olavs Hospital, Trondheim, Norway.
⁸⁹ Université Claude Bernard Lyon 1, U INSERM 1290 RESHAPE, Lyon, France.
⁹⁰ Laboratory of Epidemiology and Population Sciences, National Institute On Aging, Baltimore, MD, USA.
⁹¹ Janus Rehabilitation, Reykjavik, Iceland.
⁹² Translational Gerontology Branch, National Institute On Aging Intramural Research Program, Baltimore, MD, USA.
⁹³ UMR 1033, INSERM, University of Lyon, Hôpital Edouard Herriot, Lyon, France.
⁹⁴ Department of General Practice, Amsterdam Public Health Research Institute, Amsterdam UMC, Location VUmc, Amsterdam, The Netherlands.
⁹⁵ PHARMO Institute for Drug Outcomes Research, Utrecht, The Netherlands.
⁹⁶ Department of Hygiene and Public Health, Faculty of Medicine, Educational Foundation of Osaka Medical and Pharmaceutical University, Osaka, Japan.
⁹⁷ York Trials Unit, Department of Health Sciences, University of York, York, UK.
⁹⁸ Centre for Health Informatics, Faculty of Biology, Medicine and Health, School of Health Sciences, University of Manchester, Manchester, UK.
⁹⁹ Statistics Support Unit, Hospital del Mar Medical Research Institute, CIBER Epidemiology and Public Health (CIBERESP), Barcelona, Spain.
¹⁰⁰ MRC Epidemiology Unit, University of Cambridge, Cambridge, UK.
¹⁰¹ Center for Health Outcomes, Implementation, Community-Engaged Sciences, School of Medicine, Tulane University, New Orleans, LA, USA.
¹⁰² Department of Preventive Medicine for Locomotive Organ Disorders, 22Nd Century Medical and Research Center, The University of Tokyo, Tokyo, Japan.
¹⁰³ Health Center Can Gibert del Plà, Catalan Institute of Health, Girona, Spain.
¹⁰⁴ Department of Medical Sciences, University of Girona, Girona, Spain.
¹⁰⁵ GROICAP (Research Group), Institut Universitari d'Investigació en Atenció Primària Jordi Gol, Girona, Spain.
¹⁰⁶ 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.
¹⁰⁷ Sahlgrenska Osteoporosis Centre, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden.
¹⁰⁸ Geriatric Medicine, Region Västra Götaland, Sahlgrenska University Hospital, Gothenburg, Mölndal, Sweden.
¹⁰⁹ Department of Medicine, University of Manitoba, Winnipeg, MB, Canada.

PMID: 40848065
DOI: 10.1007/s00198-025-07607-w

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.

Keywords: FRAX; Family history; Hip fracture; Meta-analysis; Osteoporotic fractureF; Parental history.

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Conflict of interest statement

Declarations. Ethical approval and consent to participate: All individual cohorts with candidate risk factors available have been approved by their local ethics committees, and informed consent has been obtained from all study participants. General ethics approval for the use of all cohorts is also given by the University of Sheffield. This study does not contain any original studies with human participants or animals performed by any of the authors. Participant data are stored in coded, de-identified form. Only summary statistics and aggregate data are published, not allowing for the identification of individual study participants. Conflict of interest: JA Kanis led the team that developed FRAX as director of the WHO Collaborating Centre for Metabolic Bone Diseases; he is a director of Osteoporosis Research Ltd., which maintains FRAX. EV McCloskey, WD Leslie, M. Lorentzon, NC Harvey, M. Schini, E. Liu, L. Vandenput, and H. Johansson are members of the FRAX team. JA Kanis, NC Harvey, and EV McCloskey are members of the advisory body of the National Osteoporosis Guideline Group. He is a director of Osteoporosis Research Ltd., which maintains FRAX. KE Akesson has no financial interest related to FRAX and chaired the National SALAR Group for Person-Centered Care Pathway Osteoporosis. FA Anderson led the team that developed GLOW while being the director of the Center for Outcomes Research at the University of Massachusetts Medical School; he has no financial interest in FRAX. R. Azagra-Ledesma has received funding for research from Instituto Carlos III of Spanish Ministry of Health, IDIAP Jordi Gol of Catalan Government, and from Scientific Societies SEMFYC and SEIOMM. CL Bager is employed at Nordic Bioscience and owns stock in Nordic Bioscience. She declares no competing interests in relation to this work. HA Bischoff-Ferrari has no financial interest in FRAX. For the DO-HEALTH trial cohort, Prof. Bischoff-Ferrari reports independent and investigator-initiated grants from the European Commission Framework 7 Research Program, from the University of Zurich, from NESTEC, from Pfizer Consumer Healthcare, from Streuli Pharma, plus non-financial support from DNP. For the study cohort extension, she reports independent and investigator-initiated grants from Pfizer and Vifor. Further, Prof. Bischoff-Ferrari reports non-financial support from Roche Diagnostics and personal fees from Wild, Sandoz, Pfizer, Vifor, Mylan, Roche, and Meda Pharma, outside the submitted work with regard to speaker fees and travel fees. JR Center has received honoraria for speaking at educational meetings and for advisory boards from Amgen and honoraria for an advisory board from Bayer, all unrelated to this work. R. Chapurlat has no financial interest in FRAX. He has received grant funding from Amgen, UCB, Chugai, MSD, Mylan, and Medac. He has received honoraria from Amgen, UCB, Chugai, Galapagos, Biocon, AbbVie, Haoma Medica, Pfizer, Amolyt, MSD, Lilly, BMS, Novartis, Arrow, PKMed, Kyowa-Kirin, and Sanofi. C. Christiansen owns stock in Nordic Bioscience. He declares no competing interests in relation to this work. C. Cooper reports personal fees from Alliance for Better Bone Health, Amgen, Eli Lilly, GSK, Medtronic, Merck, Novartis, Pfizer, Roche, Servier, Takeda, and UCB. JAP da Silva has no financial interest in FRAX and reports personal fees from Amgen and Fresenius-Kabi, all outside the submitted work. A. Diez-Perez reports personal fees from Theramex and owns shares of Active Life Scientific, all outside the submitted work. JA Eisman declares consulting and research support from Actavis, Amgen, Aspen, Lilly, Merck Sharp and Dohme, Novartis, Sanofi-Aventis, Servier, and Theramex. PJM Elders has no financial interest in FRAX. PJM Elders reports support for the SOS study by Stichting Achmea Gezondheidszorg, Achmea, and VGZ zorgverzekeraar. Additional support was given by the Stichting Artsenlaboratorium en Trombosedienst. Outside the submitted work, she did receive independent investigator-driven grants from ZonMw, the Netherlands; de Hartstichting, the Netherlands; the European Foundation for the Study of Diabetes, Amgen, the Netherlands; TEVA, the Netherlands; and Takeda, the Netherlands. CC Gluer reports honoraria and research support from AgNovos, Amgen, Osteolabs, and UCB unrelated to this work. NC Harvey has received consultancy/lecture fees/honoraria/grant funding from Alliance for Better Bone Health, Amgen, MSD, Eli Lilly, Radius Health, Servier, Shire, UCB, Kyowa Kirin, Consilient Healthcare, Theramex, and Internis Pharma. DP Kiel has no financial interest in FRAX but has received support for his work in the Framingham Study over the past 32 years from the National Institutes of Health, AstraZeneca, Merck, Amgen, and Radius Health. MA Kotowicz has received funding from the National Health and Medical Research Council (NHMRC) Australia, the Medical Research Future Fund (MRFF) Australia, and Amgen. He has served on advisory boards for Amgen Australia, Novartis, and Eli Lilly—all unrelated to this work—and is the Director of the Geelong Bone Densitometry Service. M. Lorentzon has received lecture fees from Amgen, Lilly, Meda, Renapharma, and UCB Pharma, and consulting fees from Amgen, Radius Health, UCB Pharma, Renapharma, Parexel International, and Consilient Health, all outside the presented work. EV McCloskey has received consultancy/lecture fees/grant funding/honoraria from AgNovos, Amgen, AstraZeneca, Consilient Healthcare, Fresenius Kabi, Gilead, GSK, Hologic, Internis, Lilly, Merck, Novartis, ObsEva, Pfizer, Radius Health, Redx Oncology, Roche, Sanofi Aventis, Theramex, UCB, ViiV, Warner Chilcott, and I3 Innovus, all outside the submitted work. C. Ohlsson is listed as a coinventor on two patent applications regarding probiotics in osteoporosis treatment. TW O’Neill reports honoraria from UCB unrelated to this work. ES Orwoll reports consulting fees from Angios, Biocon, Radius, and Bayer. JA Pasco has received funding from the National Health and Medical Research Council (NHMRC) Australia, the Medical Research Future Fund (MRFF), Australia, and Amgen, all unrelated to this work. M. Schini received funding for her fellowship from the Medical Research Council Centre of Excellence for Musculoskeletal Ageing, from the Osteoporosis 2000 support group, and from Roche Diagnostics, and honoraria from MA Health care and Kyowa Kirin—all unrelated to this work. KMA Swart is an employee of the PHARMO Institute for Drug Outcomes Research. This independent research institute performs financially supported studies for the government, related healthcare authorities, and several pharmaceutical companies. NC Wright sits on the Board of Trustees of the US Bone Health and Osteoporosis Foundation and has received consulting fees from Radius and ArgenX. M. Zwart has received research funding from national societies (SEMFYC and SEIOMM). C. Beaudart, E. Biver, O. Bruyere, JA Cauley, CJ Crandall, SR Cummings, B. Dawson-Hughes, AB Dufour, S. Ferrari, Y. Fujita, S. Fujiwara, I. Goldshtein, D. Goltzman, V. Gudnason, J. Hall, D. Hans, M. Hoff, RJ Hollick, M. Huisman, M. Iki, S. Ish-Shalom, H. Johansson, G. Jones, MK Karlsson, S. Khosla, W–P Koh, F. Koromani, H. Kroger, T. Kwok, O. Lamy, A. Langhammer, B. Larijani, WD Leslie, K. Lippuner, E. Liu, FEA McGuigan, D. Mellstrom, T. Merlijn, T. Nguyen, A. Nordstrom, P. Nordstrom, B. Obermayer-Pietsch, F. Rivadeneira, A-M Schott, EJ Shiroma, K. Siggeirsdottir, EM Simonsick, E. Sornay-Rendu, R. Sund, P. Szulc, J. Tamaki, DJ Torgerson, L. Vandenput, NM van Schoor, TP van Staa, J. Vila, N. Yoshimura, and MC Zillikens declare no competing interests in relation to this work.

References

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1. Cummings SR, Nevitt MC, Browner WS, Stone K, Fox KM, Ensrud KE, Cauley J, Black D, Vogt TM, Study of Osteoporotic Fractures Research Group (1995) Risk factors for hip fracture in white women. N Engl J Med 332:767–773 - DOI - PubMed
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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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Family history of fracture and fracture risk: a meta-analysis to update the FRAX® risk assessment tool

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