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      Previous fracture and subsequent fracture risk: A meta-analysis to update FRAX

      research-article
      , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , ,
      Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA
      Prior fracture, Meta-analysis, Hip fracture, Osteoporotic fracture, Major osteoporotic fracture

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          Abstract

          Summary

          A large international meta-analysis using primary data from 64 cohorts has quantified the increased risk of fracture associated with a previous history of fracture for future use in FRAX.

          Introduction

          The aim of this study was to quantify the fracture risk associated with a prior fracture on an international basis and to explore the relationship of this risk with age, sex, time since baseline and bone mineral density (BMD).

          Methods

          We studied 665,971 men and 1,438,535 women from 64 cohorts in 32 countries followed for a total of 19.5 million person-years. The effect of a prior history of fracture on the risk of any clinical fracture, any osteoporotic fracture, major osteoporotic fracture and hip fracture alone was examined using an extended Poisson model in each cohort. Covariates examined were age, sex, BMD and duration of follow up. The results of the different studies were merged by using the weighted β-coefficients.

          Results

          A previous fracture history, compared with individuals without a prior fracture, was associated with a significantly increased risk of any clinical fracture (Hazard ratio, HR = 1.88; 95% CI = 1.72-2.07). The risk ratio was similar for the outcome of osteoporotic fracture (HR = 1.87; 95% CI = 1.69-2.07), major osteoporotic fracture (HR = 1.83; 95% CI = 1.63-2.06) or for hip fracture (HR = 1.82; 95% CI = 1.62-2.06). There was no significant difference in risk ratio between men and women. Subsequent fracture risk was marginally downward adjusted when account was taken of BMD. Low BMD explained a minority of the risk for any clinical fracture (14%), osteoporotic fracture (17%), and for hip fracture (33%). The risk ratio for all fracture outcomes related to prior fracture decreased significantly with adjustment for age and time since baseline examination.

          Conclusion

          A previous history of fracture confers an increased risk of fracture of substantial importance beyond that explained by BMD. The effect is similar in men and women. Its quantitation on an international basis permits the more accurate use of this risk factor in case finding strategies.

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          Most cited references49

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          Clinician’s Guide to Prevention and Treatment of Osteoporosis

          The Clinician’s Guide to Prevention and Treatment of Osteoporosis was developed by an expert committee of the National Osteoporosis Foundation (NOF) in collaboration with a multispecialty council of medical experts in the field of bone health convened by NOF. Readers are urged to consult current prescribing information on any drug, device, or procedure discussed in this publication.
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            European guidance for the diagnosis and management of osteoporosis in postmenopausal women

            Summary Guidance is provided in a European setting on the assessment and treatment of postmenopausal women at risk from fractures due to osteoporosis. Introduction The International Osteoporosis Foundation and European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis published guidance for the diagnosis and management of osteoporosis in 2013. This manuscript updates these in a European setting. Methods Systematic reviews were updated. Results The following areas are reviewed: the role of bone mineral density measurement for the diagnosis of osteoporosis and assessment of fracture risk; general and pharmacological management of osteoporosis; monitoring of treatment; assessment of fracture risk; case-finding strategies; investigation of patients; health economics of treatment. The update includes new information on the evaluation of bone microstructure evaluation in facture risk assessment, the role of FRAX® and Fracture Liaison Services in secondary fracture prevention, long-term effects on fracture risk of dietary intakes, and increased fracture risk on stopping drug treatment. Conclusions A platform is provided on which specific guidelines can be developed for national use.
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              Patients with prior fractures have an increased risk of future fractures: a summary of the literature and statistical synthesis.

              Numerous studies have reported increased risks of hip, spine, and other fractures among people who had previous clinically diagnosed fractures, or who have radiographic evidence of vertebral fractures. However, there is some variability in the magnitudes of associations among studies. We summarized the literature and performed a statistical synthesis of the risk of future fracture, given a history of prior fracture. The strongest associations were observed between prior and subsequent vertebral fractures; women with preexisting vertebral fractures (identified at baseline by vertebral morphometry) had approximately 4 times greater risk of subsequent vertebral fractures than those without prior fractures. This risk increases with the number of prior vertebral fractures. Most studies reported relative risks of approximately 2 for other combinations of prior and future fracture sites (hip, spine, wrist, or any site). The confidence profile method was used to derive a single pooled estimate from the studies that provided sufficient data for other combinations of prior and subsequent fracture sites. Studies of peri- and postmenopausal women with prior fractures had 2.0 (95 % CI = 1.8, 2.1) times the risk of subsequent fracture compared with women without prior fractures. For other studies (including men and women of all ages), the risk was increased by 2.2 (1.9, 2.6) times. We conclude that history of prior fracture at any site is an important risk factor for future fractures. Patients with a history of prior fracture, therefore, should receive further evaluation for osteoporosis and fracture risk.
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                Author and article information

                Contributors
                Role: Prof.
                Journal
                9100105
                Osteoporos Int
                Osteoporos Int
                Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA
                0937-941X
                1433-2965
                11 August 2023
                11 August 2023
                01 September 2023
                01 December 2023
                : 34
                : 12
                : 2027-2045
                Affiliations
                Mary McKillop Institute for Health Research, Australian Catholic University, Melbourne, Australia; Centre for Metabolic Bone Diseases, University of Sheffield, Sheffield, UK
                Mary McKillop Institute for Health Research, Australian Catholic University, Melbourne, Australia; Sahlgrenska Osteoporosis Centre, Institute of Medicine, University of Gothenburg, Sweden
                Centre for Metabolic Bone Diseases, University of Sheffield, Sheffield, UK; MRC Versus Arthritis Centre for Integrated research in Musculoskeletal Ageing, Mellanby Centre for Musculoskeletal Research, University of Sheffield, Sheffield, UK
                Mary McKillop Institute for Health Research, Australian Catholic University, Melbourne, Australia
                Clinical and Molecular Osteoporosis Research Unit, Department of Clinical Sciences, Lund University, Lund, Sweden; Department of Orthopedics, Skåne University Hospital, Malmö, Sweden
                GLOW Coordinating Center, Center for Outcomes Research, University of Massachusetts Medical School, Worcester, MA, USA
                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
                Nordic Bioscience A/S, Herlev, Denmark
                WHO Collaborating Centre for Public Health Aspects of Musculoskeletal Health and Aging, Division of Public Health, Epidemiology and Health Economics, University of Liège, Liège, Belgium; Department of Health Services Research, University of Maastricht, Maastricht, the Netherlands
                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
                Division of Bone Diseases, Department of Medicine, Geneva University Hospitals and Faculty of Medicine, University of Geneva, Geneva, Switzerland
                WHO Collaborating Centre for Public Health Aspects of Musculoskeletal Health and Aging, Division of Public Health, Epidemiology and Health Economics, University of Liège, Liège, Belgium
                Department of Epidemiology, School of Public Health, University of Pittsburgh, Pittsburgh, Philadelphia, United States.
                Skeletal Diseases Program, 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; School of Medicine Sydney, University of Notre Dame Australia, Sydney, NSW, Australia
                INSERM UMR 1033, Université Claude Bernard-Lyon1, Hôpital Edouard Herriot, Lyon, France
                Nordic Bioscience A/S, Herlev, Denmark
                MRC Lifecourse Epidemiology Centre, University of Southampton, Southampton, UK; NIHR Southampton Biomedical Research Centre, University of Southampton and University Hospitals Southampton NHS Foundation Trust, Southampton, UK; NIHR Oxford Biomedical Research Unit, University of Oxford, Oxford, UK
                Division of General Internal Medicine and Health Services Research, David Geffen School of Medicine, University of California, Los Angeles, CA, USA
                San Francisco Coordinating Center, California Pacific Medical Center Research Institute, San Francisco, CA, USA
                Coimbra Institute for Clinical and Biomedical Research, Faculty of Medicine, University of Coimbra, Coimbra, Portugal; Rheumatology Department, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal
                Bone Metabolism Laboratory, Jean Mayer US Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, MA, USA
                Department of Internal Medicine, Hospital del Mar and CIBERFES, Autonomous University of Barcelona, Barcelona, Spain
                Marcus Institute for Aging Research, Hebrew SeniorLife, Boston, MA, USA; Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA
                Skeletal Diseases Program, 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; School of Medicine Sydney, University of Notre Dame Australia, Sydney, NSW, Australia
                Petra JM Elders Department of General Practice, Amsterdam UMC, location AMC, Amsterdam Public Health Research Institute, Amsterdam, The Netherlands
                Division of Bone Diseases, Department of Medicine, Geneva University Hospitals and Faculty of Medicine, University of Geneva, Geneva, Switzerland
                Center for Medical Education and Clinical Training, Kindai University Faculty of Medicine, Osaka, Japan
                Department of Pharmacy, Yasuda Women’s University, Hiroshima, Japan
                Section Biomedical Imaging, Molecular Imaging North Competence Center, Department of Radiology and Neuroradiology, University Medical Center Schleswig-Holstein Kiel, Kiel University, Kiel, Germany
                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
                Department of Medicine, McGill University and McGill University Health Centre, Montreal, Canada
                Icelandic Heart Association, Kopavogur, Iceland; University of Iceland, Reykjavik, Iceland
                MRC Centre for Reproductive Health, University of Edinburgh, Edinburgh, UK
                Interdisciplinary Centre of Bone Diseases, Bone and Joint Department, Lausanne University Hospital (CHUV) & University of Lausanne, Lausanne, Switzerland
                Department of Neuromedicine and Movement Science, Norwegian University of Science and Technology, Trondheim, Norway; Department of Rheumatology, St Olavs Hospital, Trondheim, Norway
                Aberdeen Centre for Arthritis and Musculoskeletal Health, Epidemiology Group, University of Aberdeen, Aberdeen, UK
                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
                Department of Public Health, Kindai University Faculty of Medicine, Osaka, Japan
                Endocrine Clinic, Elisha Hospital, Haifa, Israel
                Menzies Institute for Medical Research, University of Tasmania, Hobart, Australia
                Clinical and Molecular Osteoporosis Research Unit, Department of Clinical Sciences, Lund University, Lund, Sweden; Department of Orthopaedics, Skåne University Hospital, Malmö, Sweden
                Robert and Arlene Kogod Center on Aging and Division of Endocrinology, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, MN, USA
                Marcus Institute for Aging Research, Hebrew Senior Life, Boston, MA, USA; Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA
                Healthy Longevity Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore; Singapore Institute for Clinical Sciences, Agency for Science Technology and Research (A*STAR), Singapore
                Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands; Department of Radiology and Nuclear Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands
                Deakin University, IMPACT (Institute for Mental and Physical Health and Clinical Translation), Geelong, Victoria, Australia; Barwon Health, Geelong, Victoria, Australia; Department of Medicine - Western Health, The University of Melbourne, St Albans, Victoria, Australia
                Department of Orthopedics and Traumatology, Kuopio University Hospital, Kuopio, Finland; Kuopio Musculoskeletal Research Unit, University of Eastern Finland, Kuopio, Finland
                Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong; Jockey Club Centre for Osteoporosis Care and Control, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong
                Centre of Bone Diseases, Lausanne University Hospital, Lausanne, Switzerland; Service of Internal Medicine, Lausanne University Hospital, Lausanne, Switzerland
                HUNT Research Centre, Department of Public Health and Nursing, Faculty of Medicine and Health Sciences, Norwegian; University of Science and Technology, Trondheim, Norway
                Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
                Department of Osteoporosis, Bern University Hospital, University of Bern, Bern, Switzerland
                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
                Department of General Practice, Amsterdam UMC, location AMC, Amsterdam Public Health Research Institute, Amsterdam, The Netherlands
                School of Sport Sciences, UiT The Arctic University of Norway, Tromsø, Norway; Department of Health Sciences, Swedish Winter Sports Research Centre, Mid Sweden University, Östersund, Sweden; Department of Medical Sciences, Uppsala University, Sweden
                Department of public health and caring sciences, Uppsala University, Uppsala, Sweden
                National Institute for Health Research Manchester Biomedical Research Centre, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK; Centre for Epidemiology Versus Arthritis, University of Manchester, Manchester, UK
                Department of Internal Medicine, Division of Endocrinology and Diabetology, Medical University Graz, Graz, Austria; Center for Biomarker Research in Medicine, Graz, Austria
                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
                Department of Medicine, Oregon Health and Science University, Portland, Oregon, USA
                Deakin University, Institute for Physical and Mental Health and Clinical Translation (IMPACT), Geelong, Australia; Department of Medicine-Western Health, The University of Melbourne, St Albans, Australia; Barwon Health, Geelong, Australia; Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia
                Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands
                Université Claude Bernard Lyon 1, U INSERM 1290 RESHAPE, Lyon, France
                Laboratory of Epidemiology and Population Sciences, National Institute on Aging, Baltimore, Maryland, USA
                Icelandic Heart Association, Kopavogur, Iceland; Janus Rehabilitation, Reykjavik, Iceland
                Translational Gerontology Branch, National Institute on Aging Intramural Research Program, Baltimore, Maryland
                INSERM UMR 1033, University of Lyon, Hôpital Edouard Herriot, Lyon, FranceINSERM
                Kuopio Musculoskeletal Research Unit, University of Eastern Finland, Kuopio, Finland
                Department of General Practice, Amsterdam UMC, location VUmc, Amsterdam Public Health Research Institute, Amsterdam, The Netherlands; PHARMO Institute for Drug Outcomes Research, Utrecht, The Netherlands
                INSERM UMR 1033, University of Lyon, Hôpital Edouard Herriot, Lyon, France
                Department of Hygiene and Public Health, Faculty of Medicine, Educational Foundation of Osaka Medical and Pharmaceutical University, Osaka, Japan
                York Trials Unit, Department of Health Sciences, University of York, York, UK
                Department of Epidemiology and Data Science, Amsterdam Public Health Research Institute, VU University Medical Center, Amsterdam, The Netherlands
                Centre for Health Informatics, Faculty of Biology, Medicine and Health, School of Health Sciences, University of Manchester, Manchester, UK
                Statistics Support Unit, Hospital del Mar Medical Research Institute, CIBER Epidemiology and Public Health (CIBERESP), Barcelona, Spain
                MRC Epidemiology Unit, University of Cambridge, Cambridge, United Kingdom
                Department of Epidemiology, University of Alabama at Birmingham, Birmingham, Alabama, USA
                Department of Preventive Medicine for Locomotive Organ Disorders, The University of Tokyo Hospital, Tokyo, Japan
                Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands
                Health Center Can Gibert del Plà, Catalan Institute of Health, Girona, Spain; Department of Medical Sciences, University of Girona, Girona, Spain; GROIMAP/GROICAP (research groups), Unitat de Suport a la Recerca Girona, Institut Universitari d’investigació en Atenció Primària Jordi Gol, Girona, Spain
                PRECIOSA-Fundación para la investigación, Barberà del Vallés, Barcelona, Spain
                Mary McKillop Institute for Health Research, Australian Catholic University, Melbourne, Australia; Sahlgrenska Osteoporosis Centre, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
                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
                Mary McKillop Institute for Health Research, Australian Catholic University, Melbourne, Australia; Sahlgrenska Osteoporosis Centre, Institute of Medicine, University of Gothenburg, Sweden; Region Västra Götaland, Geriatric Medicine, Sahlgrenska University Hospital, Mölndal, Sweden
                Department of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada
                Author notes
                Corresponding author: Prof. John A Kanis, Centre for Metabolic Bone Diseases University of Sheffield Medical School Sheffield, UK, Tel: +44 114 285 1109, w.j.Pontefract@ 123456sheffield.ac.uk
                Article
                EMS187236
                10.1007/s00198-023-06870-z
                7615305
                37566158
                9f8a96e3-c78d-4c5b-ab4f-62e794c098a3

                This work is licensed under a BY 4.0 International license.

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                Categories
                Article

                Orthopedics
                prior fracture,meta-analysis,hip fracture,osteoporotic fracture,major osteoporotic fracture

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