IDIAPJGol
Published September 1, 2025 | Version v1
Journal article Open

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

Authors/Creators

  • 1. Univ Sheffield, Ctr Metab Bone Dis, Sheffield, S Yorkshire, England; Univ Sheffield, Ctr Integrated Res Musculoskeletal Ageing, Mellanby Ctr Musculoskeletal Res, Div Clin Med,Sch Med & Populat Hlth,Med Sch, Sheffield, S Yorkshire, England
  • 2. Univ Sheffield, Ctr Metab Bone Dis, Sheffield, S Yorkshire, England
  • 3. Flinders Univ S Australia, Coll Med & Publ Hlth, Adelaide, SA, Australia
  • 4. Lund Univ, Clin & Mol Osteoporosis Res Unit, Dept Clin Sci, Lund, Sweden; Skane Univ Hosp, Dept Orthoped, Malmo, Sweden
  • 5. Univ Massachusetts, Sch Med, GLOW Coordinating Ctr, Ctr Outcomes Res, Worcester, MA USA
  • 6. Autonomous Univ Barcelona, Dept Med, Barcelona, Spain; Catalan Inst Hlth, Hlth Ctr Badia Valles, Barcelona, Spain; Inst Univ Invest Atencio Primaria Jordi Gol, GROIMAP Res Grp, Unitat Suport Metropolitana Nord, Barcelona, Spain; PRECIOSA Fdn Invest, Barcelona, Spain
  • 7. Nord Biosci AS, Herlev, Denmark
  • 8. Univ Namur, NAmur Res Inst LIfe Sci NARILIS, Publ Hlth Aging Res & Epidemiol PHARE Grp, Res Unit Clin Pharmacol & Toxicol URPC, Namur, Belgium
  • 9. Univ Hosp, Dept Aging Med & Aging Res, Zurich, Switzerland; Univ Zurich, Zurich, Switzerland; Univ Zurich, Ctr Aging & Mobil, Zurich, Switzerland; City Hosp, Zurich, Switzerland
  • 10. Geneva Univ Hosp, Div Bone Dis, Dept Med, Geneva, Switzerland; Univ Geneva, Fac Med, Geneva, Switzerland
  • 11. Univ Liege, Res Unit Publ Hlth Epidemiol & Hlth Econ, Liege, Belgium
  • 12. Univ Pittsburgh, Dept Epidemiol, Sch Publ Hlth, Pittsburgh, PA USA
  • 13. Garvan Inst Med Res, Sydney, NSW, Australia; Univ New South Wales Sydney, St Vincents Clin Sch, Sch Med & Hlth, Sydney, NSW, Australia
  • 14. Univ Claude Bernard Lyon1, Hop Edouard Herriot, INSERM, UMR 1033, Lyon, France
  • 15. Univ Southampton, MRC Lifecourse Epidemiol Ctr, Southampton, Hants, England; Univ Southampton, NIHR Southampton Biomed Res Ctr, Southampton, Hants, England; Univ Hosp Southampton NHS Fdn Trust, Southampton, Hants, England; Univ Oxford, NIHR Oxford Biomed Res, Oxford, England
  • 16. Univ Calif Los Angeles, Div Gen Internal Med & Hlth Serv Res, David Geffen Sch Med, Los Angeles, CA USA
  • 17. Calif Pacific Med Ctr, Res Inst, San Francisco Coordinating Ctr, San Francisco, CA USA
  • 18. Univ Coimbra, Fac Med, Coimbra Inst Clin & Biomed Res, Coimbra, Portugal; Univ Hosp, Dept Rheumatol, Coimbra, Portugal; Univ Coimbra, Coimbra, Portugal
  • 19. Tufts Univ, Bone Metab Lab, Jean Mayer US Dept Agr, Human Nutr Res Ctr Aging, Boston, MA USA
  • 20. Autonomous Univ Barcelona, Dept Internal Med, Hosp del Mar, Barcelona, Spain; Autonomous Univ Barcelona, CIBERFES, Barcelona, Spain
  • 21. Hebrew SeniorLife, Marcus Inst Aging Res, Boston, MA USA; Harvard Med Sch, Dept Med, Beth Israel Deaconess Med Ctr, Boston, MA USA
  • 22. Univ New South Wales Sydney, St Vincents Clin Sch, Sch Med & Hlth, Sydney, NSW, Australia; Garvan Inst Med Res, Skeletal Dis Program, Sydney, NSW, Australia; Univ Notre Dame Australia, Sch Med Sydney, Sydney, NSW, Australia
  • 23. Amsterdam Publ Hlth Res Inst, Dept Gen Practice, Amsterdam UMC, Locat AMC, Amsterdam, Netherlands
  • 24. Kansai Med Univ, Dept Hyg & Publ Hlth, Fac Med, Osaka, Japan
  • 25. Yasuda Womens Univ, Dept Pharm, Hiroshima, Japan
  • 26. Univ Kiel, Univ Med Ctr Schleswig Holstein, Mol Imaging North Competence Ctr, Dept Radiol & Neuroradiol,Sect Biomed Imaging, Kiel, Germany
  • 27. Maccabi Healthcare Serv, Maccabitech Inst Res & Innovat, Tel Aviv, Israel; Tel Aviv Univ, Dept Epidemiol & Prevent Med, Sch Publ Hlth, Sackler Fac Med, Tel Aviv, Israel
  • 28. McGill Univ, Dept Med, Montreal, PQ, Canada; McGill Univ, Ctr Hlth, Montreal, PQ, Canada
  • 29. Iceland Heart Assoc, Kopavogur, Iceland; Univ Iceland, Reykjavik, Iceland
  • 30. Univ Edinburgh, MRC Ctr Reprod Hlth, Edinburgh, Midlothian, Scotland
  • 31. Lausanne Univ Hosp, Ctr Bone Dis, Bone & Joint Dept, Lausanne, Switzerland
  • 32. Norwegian Univ Sci & Technol, Dept Neuromed & Movement Sci, Trondheim, Norway; St Olavs Hosp, Dept Rheumatol, Trondheim, Norway
  • 33. Univ Aberdeen, Aberdeen Ctr Arthrit & Musculoskeletal Hlth, Epidemiol Grp, Aberdeen, Scotland
  • 34. Vrije Univ Amsterdam Med Ctr, Dept Epidemiol & Data Sci, Amsterdam Publ Hlth Res Inst, Amsterdam, Netherlands; Vrije Univ Amsterdam, Dept Sociol, Amsterdam, Netherlands
  • 35. Kindai Univ, Fac Med, Dept Publ Hlth, Osaka, Japan
  • 36. Elisha Hosp, Endocrine Clin, Haifa, Israel
  • 37. Univ Tasmania, Menzies Inst Med Res, Hobart, Tas, Australia
  • 38. Lund Univ, Clin & Mol Osteoporosis Res Unit, Dept Clin Sci, Lund, Sweden; Skane Univ Hosp, Dept Orthopaed, Malmo, Sweden
  • 39. Mayo Clin, Mayo Clin Coll Med, Robert & Arlene Kogod Ctr Aging, Rochester, MN USA; Mayo Clin, Mayo Clin Coll Med, Div Endocrinol, Rochester, MN USA
  • 40. Natl Univ Singapore, Hlth Longev Translat Res Programme, Yong Loo Lin Sch Med, Singapore, Singapore; A STAR Inst Human Dev & Potential, Singapore, Singapore
  • 41. Erasmus MC, Dept Internal Med, Rotterdam, Netherlands; Erasmus MC, Dept Radiol & Nucl Med, Rotterdam, Netherlands
  • 42. Deakin Univ, IMPACT Inst Mental & Phys Hlth & Clin Translat, Geelong, Vic, Australia; Barwon Hlth, Geelong, Vic, Australia; Univ Melbourne, Dept Med Western Hlth, St Albans, Vic, Australia
  • 43. Kuopio Univ Hosp, Dept Orthoped & Traumatol, Kuopio, Finland; Univ Eastern Finland, Kuopio Musculoskeletal Res Unit, Kuopio, Finland
  • 44. Chinese Univ Hong Kong, Dept Med & Therapeut, Fac Med, Hong Kong, Peoples R China; Chinese Univ Hong Kong, Jockey Club Ctr Osteoporosis Care & Control, Fac Med, Hong Kong, Peoples R China
  • 45. Lausanne Univ Hosp, Ctr Bone Dis, Lausanne, Switzerland; Lausanne Univ Hosp, Serv Internal Med, Lausanne, Switzerland
  • 46. Norwegian Univ Sci & Technol, HUNT Res Ctr, Dept Publ Hlth & Nursing, NTNU, Levanger, Norway; Nord Trondelag Hosp Trust, Levanger Hosp, Levanger, Norway
  • 47. Univ Tehran Med Sci, Endocrinol & Metab Res Ctr, Endocrinol & Metab Clin Sci Inst, Tehran, Iran
  • 48. Univ Bern, Fac Med, ARTORG Ctr Biomed Engn Res, Bern, Switzerland
  • 49. Univ Gothenburg, Geriatr Med, Dept Internal Med & Clin Nutr, Inst Med,Sahlgrenska Acad, Gothenburg, Sweden; Sahlgrenska Univ Hosp Molndal, Geriatr Med, Molndal, Sweden
  • 50. Lund Univ, Clin & Mol Osteoporosis Res Unit, Dept Clin Sci, Lund, Sweden
  • 51. Univ Technol Sydney, Sch Biomed Engn, Sydney, NSW, Australia; UNSW Sydney, UNSW Med, Sch Populat Hlth, Kensington, NSW, Australia; Tam Anh Hosp, Tam Anh Res Inst, Ho Chi Minh City, Vietnam
  • 52. Uppsala Univ, Dept Med Sci, Uppsala, Sweden; Arctic Univ Norway, Sch Sport Sci, Tromso, Norway
  • 53. Uppsala Univ, Dept Publ Hlth & Caring Sci, Clin Geriatr, Uppsala, Sweden
  • 54. Univ Manchester, Ctr Epidemiol Versus Arthrit, Caring Sci, Clin Geriatr, Manchester, Lancs, England
  • 55. Med Univ Graz, Endocrine Lab Platform, Div Endocrinol & Diabetol, Dept Internal Med, Auenbruggerpl 15, A-8036 Graz, Austria
  • 56. Univ Gothenburg, Sahlgrenska Osteoporosis Ctr, Dept Internal Med & Clin Nutr, Inst Med,Sahlgrenska Acad, Gothenburg, Sweden; Sahlgrens Univ Hosp, Dept Drug Treatment, Gothenburg, Sweden
  • 57. Oregon Hlth & Sci Univ, Dept Med, Portland, OR USA
  • 58. Deakin Univ, IMPACT Inst Mental & Phys Hlth & Clin Translat, Geelong, Vic, Australia; Barwon Hlth, Geelong, Vic, Australia; Univ Melbourne, Dept Med Western Hlth, St Albans, Vic, Australia; Monash Univ, Dept Epidemiol & Prevent Med, Melbourne, Vic, Australia
  • 59. Erasmus MC, Dept Internal Med, Rotterdam, Netherlands
  • 60. Norwegian Univ Sci & Technol, Dept Publ Hlth & Nursing, Trondheim, Norway; St Olavs Hosp, Dept Gynecol, Trondheim, Norway
  • 61. Univ Claude Bernard Lyon 1, INSERM, U1290, RESHAPE, Lyon, France
  • 62. NIA, Lab Epidemiol & Populat Sci, Baltimore, MD USA
  • 63. Iceland Heart Assoc, Kopavogur, Iceland; Janus Rehabil, Reykjavik, Iceland
  • 64. NIA, Translat Gerontol Branch, Intramural Res Program, Baltimore, MD USA
  • 65. Univ Lyon, Hop Edouard Herriot, INSERM, UMR 1033, Lyon, France
  • 66. Univ Eastern Finland, Kuopio Musculoskeletal Res Unit, Kuopio, Finland
  • 67. Locat VUmc, Amsterdam UMC, Dept Gen Practice, Amsterdam Publ Hlth Res Inst, Amsterdam, Netherlands; Pharmo Inst Drug Outcomes Res, Utrecht, Netherlands
  • 68. Osaka Med & Pharmaceut Univ, Dept Hyg & Publ Hlth, Fac Med, Educ Fdn, Osaka, Japan
  • 69. Univ York, York Trials Unit, Dept Hlth Sci, York, N Yorkshire, England
  • 70. Vrije Univ Amsterdam Med Ctr, Dept Epidemiol & Data Sci, Amsterdam Publ Hlth Res Inst, Amsterdam, Netherlands
  • 71. Univ Manchester, Sch Hlth Sci, Ctr Hlth Informat, Fac Biol Med & Hlth, Manchester, Lancs, England
  • 72. Hosp del Mar, Med Res Inst, CIBER Epidemiol & Publ Hlth CIBERESP, Stat Support Unit, Barcelona, Spain
  • 73. Univ Cambridge, MRC Epidemiol Unit, Cambridge, England
  • 74. Tulane Univ, Sch Med, Ctr Hlth Outcomes, Implementat,Community Engaged Sci, New Orleans, LA USA
  • 75. Univ Tokyo, Dept Prevent Med Locomot Organ Disorders, 22Nd Century Med & Res Ctr, Tokyo, Japan
  • 76. Catalan Inst Hlth, Hlth Ctr Can Gibert Pla, Girona, Spain; Univ Girona, Dept Med Sci, Girona, Spain; Inst Univ Invest Atencio Primaria Jordi Gol, GROICAP Res Grp, Girona, Spain
  • 77. Univ Sheffield, Ctr Integrated Res Musculoskeletal Ageing, Mellanby Ctr Musculoskeletal Res, Div Clin Med,Sch Med & Populat Hlth,Med Sch, Sheffield, S Yorkshire, England
  • 78. Univ Gothenburg, Sahlgrenska Osteoporosis Ctr, Dept Internal Med & Clin Nutr, Inst Med,Sahlgrenska Acad, Gothenburg, Sweden
  • 79. Univ Southampton, MRC Lifecourse Epidemiol Ctr, Southampton, Hants, England; Univ Southampton, NIHR Southampton Biomed Res Ctr, Southampton, Hants, England; Univ Hosp Southampton NHS Fdn Trust, Southampton, Hants, England
  • 80. Univ Gothenburg, Inst Med, Sahlgrenska Osteoporosis Ctr, Gothenburg, Sweden; Sahlgrens Univ Hosp, Geriatr Med, Gothenburg, Sweden
  • 81. Univ Manitoba, Dept Med, Winnipeg, MB, Canada

Description

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

Notes

The Osteoporotic Fractures in Men (MrOS) Study is supported by National Institutes of Health funding. The following institutes provide support: the National Institute on Aging (NIA), the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), the National Center for Advancing Translational Sciences (NCATS), and NIH Roadmap for Medical Research under the following grant numbers: U01 AG027810, U01 AG042124, U01 AG042139, U01 AG042140, U01 AG042143, U01 AG042145, U01 AG042168, U01 AR066160, R01 AG066671, and UL1 TR000128. MrOS Sweden is supported by the Swedish Research Council, ALF/LUA research grants in Gothenburg, the King Gustav V, Queen Victoria Frimurarestiftelse Research Foundation, and ALF and Region Skane research grants in Malmo. The WHI program is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services through contracts 75N92021D00001, 75N92021D00002, 75N92021D00003, 75N92021D00004, and 75N92021D00005. The OsteoLaus study was supported by research grants from Lausanne University Hospital (CHUV-Strategic plan funds) and the Swiss National Science Foundation (grants 32473B-156978).

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