FRAX; Family history; Hip fracture; Meta-analysis; Osteoporotic fractureF; Parental history; Humans; Female; Male; Risk Assessment/methods; Hip Fractures/epidemiology; Hip Fractures/genetics; Hip Fractures/physiopathology; Bone Density/physiology; Aged; Middle Aged; Incidence; Osteoporotic Fractures/epidemiology; Osteoporotic Fractures/genetics; Osteoporotic Fractures/physiopathology; Osteoporotic Fractures/etiology; Bone Density; Hip Fractures; Osteoporotic Fractures; Risk Assessment; Endocrinology, Diabetes and Metabolism
Abstract :
[en] [en] UNLABELLED: 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.
Disciplines :
Geriatrics
Author, co-author :
McCloskey, Eugene V ; Centre for Metabolic Bone Diseases, University of Sheffield, Sheffield, UK. e.v.mccloskey@sheffield.ac.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. e.v.mccloskey@sheffield.ac.uk
Johansson, Helena; Centre for Metabolic Bone Diseases, University of Sheffield, Sheffield, UK
Liu, Enwu; College of Medicine and Public Health, Flinders University, Adelaide, Australia
Åkesson, Kristina E; Clinical and Molecular Osteoporosis Research Unit, Department of Clinical Sciences, Lund University, Lund, Sweden ; Department of Orthopedics, Skåne University Hospital, Malmö, Sweden
Anderson, Fred A; GLOW Coordinating Center, Center for Outcomes Research, University of Massachusetts Medical School, Worcester, MA, USA
Azagra-Ledesma, Rafael ; Department of Medicine, Autonomous University of Barcelona, Barcelona, Spain ; Health Centre Badia del Valles, Catalan Institute of Health, Barcelona, Spain ; 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 ; PRECIOSA-Fundación Para La Investigación, Barberà del Vallés, Barcelona, Spain
Beaudart, Charlotte; 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
Bischoff-Ferrari, Heike A; Department of Aging Medicine and Aging Research, University Hospital, Zurich, and University of Zurich, Zurich, Switzerland ; Centre On Aging and Mobility, University of Zurich and City Hospital, Zurich, Switzerland
Biver, Emmanuel ; Division of Bone Diseases, Department of Medicine, Geneva University Hospitals and Faculty of Medicine, University of Geneva, Geneva, Switzerland
Bruyère, Olivier ; Université de Liège - ULiège > Département des sciences de la santé publique > Santé publique, Epidémiologie et Economie de la santé
Cauley, Jane A ; Department of Epidemiology, School of Public Health, University of Pittsburgh, Pittsburgh, Philadelphia, USA
Center, Jacqueline R ; Garvan Institute of Medical Research, Sydney, NSW, Australia ; St Vincent's Clinical School, School of Medicine and Health, University of New South Wales Sydney, Sydney, NSW, Australia
Chapurlat, Roland; INSERM UMR 1033, Université Claude Bernard-Lyon1, Hôpital Edouard Herriot, Lyon, France
Cooper, Cyrus; MRC Lifecourse Epidemiology Centre, University of Southampton, Southampton, UK ; NIHR Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, UK ; NIHR Oxford Biomedical Research Unit, University of Oxford, Oxford, UK
Crandall, Carolyn J; Division of General Internal Medicine and Health Services Research, David Geffen School of Medicine, University of California, Los Angeles, CA, USA
Cummings, Steven R; San Francisco Coordinating Center, California Pacific Medical Center Research Institute, San Francisco, CA, USA
da Silva, José A P ; Coimbra Institute for Clinical and Biomedical Research, Faculty of Medicine, University of Coimbra, Coimbra, Portugal ; Rheumatology Department, University Hospital and University of Coimbra, Coimbra, Portugal
Dawson-Hughes, Bess ; Bone Metabolism Laboratory, Jean Mayer US Department of Agriculture Human Nutrition Research Center On Aging, Tufts University, Boston, MA, USA
Diez-Perez, Adolfo; Department of Internal Medicine, Hospital del Mar and CIBERFES, Autonomous University of Barcelona, Barcelona, Spain
Dufour, Alyssa B; Marcus Institute for Aging Research, Hebrew SeniorLife, Boston, MA, USA ; Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
Eisman, John A; St Vincent's Clinical School, School of Medicine and Health, University of New South Wales Sydney, Sydney, NSW, Australia ; Skeletal Diseases Program, Garvan Institute of Medical Research, Sydney, NSW, Australia ; School of Medicine Sydney, University of Notre Dame Australia, Sydney, NSW, Australia
Elders, Petra J M; Department of General Practice, Amsterdam UMC, Location AMC, Amsterdam Public Health Research Institute, Amsterdam, The Netherlands
Ferrari, Serge; Division of Bone Diseases, Department of Medicine, Geneva University Hospitals and Faculty of Medicine, University of Geneva, Geneva, Switzerland
Fujita, Yuki; Department of Hygiene and Public Health, Faculty of Medicine, Kansai Medical University, Osaka, Japan
Fujiwara, Saeko; Department of Pharmacy, Yasuda Women's University, Hiroshima, Japan
Glüer, Claus-Christian; Section Biomedical Imaging, Molecular Imaging North Competence Center, Department of Radiology and Neuroradiology, University Medical Center Schleswig-Holstein Kiel, Kiel University, Kiel, Germany
Goldshtein, Inbal; Maccabitech Institute of Research and Innovation, Maccabi Healthcare Services, Tel Aviv, Israel ; Department of Epidemiology and Preventive Medicine, School of Public Health, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
Goltzman, David; Department of Medicine, McGill University and McGill University Health Centre, Montreal, Canada
Gudnason, Vilmundur; Icelandic Heart Association, Kopavogur, Iceland ; University of Iceland, Reykjavik, Iceland
Hall, Jill; MRC Centre for Reproductive Health, University of Edinburgh, Edinburgh, UK
Hans, Didier ; Centre of Bone Diseases, Bone and Joint Department, Lausanne University Hospital, Lausanne, Switzerland
Hoff, Mari ; Department of Neuromedicine and Movement Science, Norwegian University of Science and Technology, Trondheim, Norway ; Department of Rheumatology, St Olavs Hospital, Trondheim, Norway
Hollick, Rosemary J; Aberdeen Centre for Arthritis and Musculoskeletal Health, Epidemiology Group, University of Aberdeen, Aberdeen, UK
Huisman, Martijn; Department of Epidemiology and Data Science, Amsterdam Public Health Research Institute, VU University Medical Center, Amsterdam, The Netherlands ; Department of Sociology, VU University, Amsterdam, The Netherlands
Iki, Masayuki ; Department of Public Health, Faculty of Medicine, Kindai University, Osaka, Japan
Ish-Shalom, Sophia; Endocrine Clinic, Elisha Hospital, Haifa, Israel
Jones, Graeme; Menzies Institute for Medical Research, University of Tasmania, Hobart, Australia
Karlsson, Magnus K; Clinical and Molecular Osteoporosis Research Unit, Department of Clinical Sciences, Lund University, Lund, Sweden ; Department of Orthopaedics, Skåne University Hospital, Malmö, Sweden
Khosla, Sundeep; Robert and Arlene Kogod Center On Aging and Division of Endocrinology, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, MN, USA
Kiel, Douglas P; Marcus Institute for Aging Research, Hebrew SeniorLife, Boston, MA, USA ; Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
Koh, Woon-Puay; Healthy Longevity Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore ; A*STAR Institute for Human Development and Potential, Singapore, Singapore
Koromani, Fjorda; Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands ; Department of Radiology and Nuclear Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands
Kotowicz, Mark A ; IMPACT (Institute for Mental and Physical Health and Clinical Translation), Deakin University, Geelong, VIC, Australia ; Barwon Health, Geelong, VIC, Australia ; Department of Medicine - Western Health, The University of Melbourne, St Albans, Victoria, Australia
Kröger, Heikki ; Department of Orthopedics and Traumatology, Kuopio University Hospital, Kuopio, Finland ; Kuopio Musculoskeletal Research Unit, University of Eastern Finland, Kuopio, Finland
Kwok, Timothy; Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, Hong Kong ; Jockey Club Centre for Osteoporosis Care and Control, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, Hong Kong
Lamy, Olivier; Centre of Bone Diseases, Lausanne University Hospital, Lausanne, Switzerland ; Service of Internal Medicine, Lausanne University Hospital, Lausanne, Switzerland
Langhammer, Arnulf ; HUNT Research Centre, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Levanger, Norway ; Levanger Hospital, Nord-Trøndelag Hospital Trust, Levanger, Norway
Larijani, Bagher ; Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
Lippuner, Kurt; Faculty of Medicine, ARTORG Center for Biomedical Engineering Research, University of Bern, Bern, Switzerland
Mellström, Dan; Geriatric Medicine, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden ; Geriatric Medicine, Sahlgrenska University Hospital Mölndal, Mölndal, Sweden
McGuigan, Fiona E A; Clinical and Molecular Osteoporosis Research Unit, Department of Clinical Sciences, Lund University, Lund, Sweden
Merlijn, Thomas; Department of General Practice, Amsterdam UMC, Location AMC, Amsterdam Public Health Research Institute, Amsterdam, The Netherlands
Nguyen, Tuan V ; School of Biomedical Engineering, University of Technology Sydney, Sydney, Australia ; School of Population Health, UNSW Medicine, UNSW Sydney, Kensington, Australia ; Tam Anh Research Institute, Tam Anh Hospital, Ho Chi Minh City, Vietnam
Nordström, Anna; Department of Medical Sciences, Uppsala University, Uppsala, Sweden ; School of Sport Sciences, Arctic University of Norway, Tromsø, Norway
Nordström, Peter ; Department of Public Health and Caring Sciences, Clinical Geriatrics, Uppsala University, Uppsala, Sweden
O Neill, Terence W; Caring Sciences, Clinical Geriatrics, Centre for Epidemiology Versus Arthritis, University of Manchester, Manchester, UK
Obermayer-Pietsch, Barbara ; Div. of Endocrinology and Diabetology, Dept. of Internal Medicine, Medical University Graz, Endocrine Lab Platform, Auenbruggerplatz 15, 8036, Graz, Austria
Ohlsson, Claes; Sahlgrenska Osteoporosis Centre, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden ; Department of Drug Treatment, Sahlgrenska University Hospital, Region Västra Götaland, Gothenburg, Sweden
Orwoll, Eric S ; Department of Medicine, Oregon Health and Science University, Portland, OR, USA
Pasco, Julie A ; IMPACT (Institute for Mental and Physical Health and Clinical Translation), Deakin University, Geelong, VIC, Australia ; Barwon Health, Geelong, VIC, Australia ; Department of Medicine - Western Health, The University of Melbourne, St Albans, Victoria, Australia ; Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia
Rivadeneira, Fernando; Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands
Schei, Berit; Department of Public Health and Nursing, Norwegian University of Science and Technology, Trondheim, Norway ; Department of Gynecology, St Olavs Hospital, Trondheim, Norway
Schott, Anne-Marie ; Université Claude Bernard Lyon 1, U INSERM 1290 RESHAPE, Lyon, France
Shiroma, Eric J; Laboratory of Epidemiology and Population Sciences, National Institute On Aging, Baltimore, MD, USA
Simonsick, Eleanor M ; Translational Gerontology Branch, National Institute On Aging Intramural Research Program, Baltimore, MD, USA
Sornay-Rendu, Elisabeth; UMR 1033, INSERM, University of Lyon, Hôpital Edouard Herriot, Lyon, France
Sund, Reijo ; Kuopio Musculoskeletal Research Unit, University of Eastern Finland, Kuopio, Finland
Swart, Karin M A; Department of General Practice, Amsterdam Public Health Research Institute, Amsterdam UMC, Location VUmc, Amsterdam, The Netherlands ; PHARMO Institute for Drug Outcomes Research, Utrecht, The Netherlands
Szulc, Pawel; UMR 1033, INSERM, University of Lyon, Hôpital Edouard Herriot, Lyon, France
Tamaki, Junko; Department of Hygiene and Public Health, Faculty of Medicine, Educational Foundation of Osaka Medical and Pharmaceutical University, Osaka, Japan
Torgerson, David J; York Trials Unit, Department of Health Sciences, University of York, York, UK
van Schoor, Natasja M; Department of Epidemiology and Data Science, Amsterdam Public Health Research Institute, VU University Medical Center, Amsterdam, The Netherlands
van Staa, Tjeerd P ; Centre for Health Informatics, Faculty of Biology, Medicine and Health, School of Health Sciences, University of Manchester, Manchester, UK
Vila, Joan; Statistics Support Unit, Hospital del Mar Medical Research Institute, CIBER Epidemiology and Public Health (CIBERESP), Barcelona, Spain
Wareham, Nicholas J; MRC Epidemiology Unit, University of Cambridge, Cambridge, UK
Wright, Nicole C; Center for Health Outcomes, Implementation, Community-Engaged Sciences, School of Medicine, Tulane University, New Orleans, LA, USA
Yoshimura, Noriko ; Department of Preventive Medicine for Locomotive Organ Disorders, 22Nd Century Medical and Research Center, The University of Tokyo, Tokyo, Japan
Zillikens, M Carola ; Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands
Zwart, Marta ; Health Center Can Gibert del Plà, Catalan Institute of Health, Girona, Spain ; Department of Medical Sciences, University of Girona, Girona, Spain ; GROICAP (Research Group), Institut Universitari d'Investigació en Atenció Primària Jordi Gol, Girona, Spain
Schini, Marian; 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
Vandenput, Liesbeth; Sahlgrenska Osteoporosis Centre, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
Harvey, Nicholas C; MRC Lifecourse Epidemiology Centre, University of Southampton, Southampton, UK ; NIHR Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, UK
Lorentzon, Mattias; Sahlgrenska Osteoporosis Centre, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden ; Geriatric Medicine, Region Västra Götaland, Sahlgrenska University Hospital, Gothenburg, Mölndal, Sweden
Leslie, William D ; Department of Medicine, University of Manitoba, Winnipeg, MB, Canada
Kanis, John A; Centre for Metabolic Bone Diseases, University of Sheffield, Sheffield, UK
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.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 Malm\u00F6. 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).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\u2014all 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.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.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.We are grateful to Dr. \u00D6sten Ljunggren for contributing the MrOS Sweden cohort. UK Biobank data are included under approved access agreement 3593. The authors acknowledge the Manitoba Centre for Health Policy for the use of Manitoba data contained in the Population Health Research Data Repository (HIPC 2016/2017-29). The results and conclusions are those of the authors and no official endorsement by the Manitoba Centre for Health Policy, Manitoba Health, Seniors and Active Living, or other data providers is intended or should be inferred. The authors also acknowledge support from the UK Medical Research Council (MC_PC_21003; MC_PC_21001), UK Medical Research Foundation (MRF-145-0011-DG-HARV-C0913), and NIHR Southampton Biomedical Research Centre. For the purpose of Open Access, the author has applied a Creative Commons Attribution (CC BY) licence to any Author Accepted Manuscript version arising from this submission.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\u2014all unrelated to this work\u2014and is the Director of the Geelong Bone Densitometry Service.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.
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