Epidemiology; FRAX; Fracture risk; Glucocorticoids; Hip fracture; Major osteoporotic fracture; Meta-analysis; Osteoporosis; Rheumatoid arthritis; Risk factors; Humans; Female; Male; Middle Aged; Bone Density/physiology; Risk Assessment/methods; Aged; Adult; Aged, 80 and over; Young Adult; Risk Factors; Sex Factors; Age Factors; Algorithms; Hip Fractures/etiology; Hip Fractures/physiopathology; Osteoporotic Fractures/etiology; Osteoporotic Fractures/physiopathology; Osteoporotic Fractures/epidemiology; Arthritis, Rheumatoid/epidemiology; Arthritis, Rheumatoid/complications; Arthritis, Rheumatoid/physiopathology; Arthritis, Rheumatoid; Bone Density; Hip Fractures; Osteoporotic Fractures; Risk Assessment; Endocrinology, Diabetes and Metabolism
Abstract :
[en] [en] UNLABELLED: The relationship between rheumatoid arthritis (RA) and fracture risk was estimated in an international meta-analysis of individual-level data from 29 prospective cohorts. RA was associated with an increased fracture risk in men and women, and these data will be used to update FRAX®.
INTRODUCTION: RA is a well-documented risk factor for subsequent fracture that is incorporated into the FRAX algorithm. The aim of this study was to evaluate, in an international meta-analysis, the association between rheumatoid arthritis and subsequent fracture risk and its relation to sex, age, duration of follow-up, and bone mineral density (BMD) with a view to updating FRAX.
METHODS: The resource comprised 1,909,896 men and women, aged 20-116 years, from 29 prospective cohorts in which the prevalence of RA was 3% or less (primary analysis) and an additional 17 cohorts with a prevalence greater than 3% (supplementary analysis). The association between RA and fracture risk (any clinical fracture, osteoporotic fracture, major osteoporotic fracture (MOF), and hip fracture) was examined using an extension of the Poisson regression model in each cohort and each sex, followed by random-effects meta-analyses of the weighted beta coefficients.
RESULTS: In the primary analysis, RA was reported in 1.3% of individuals. During 15,683,133 person-years of follow-up, 139,002 fractures occurred, of which 27,518 were hip fractures. RA was associated with an increased risk of any clinical fracture (hazard ratio [HR] 1.49, 95% confidence interval [CI] 1.35-1.65). The HRs were of similar magnitude for osteoporotic fracture and MOF but higher for hip fracture (HR = 2.23; 95% CI 1.85-2.69). For hip fracture, there was a significant interaction with age with higher HRs at younger ages. HRs did not differ between men and women and were independent of exposure to glucocorticoids and femoral neck BMD. Lower HRs were observed in the supplementary analysis cohorts, particularly in those with a high apparent prevalence of RA, possibly from conflation of RA with osteoarthritis.
CONCLUSIONS: A diagnosis of RA confers an increased risk of fracture that is largely independent of BMD, sex, and corticosteroids. RA should be retained as a risk factor in future iterations of FRAX with updated risk functions to improve fracture risk prediction.
Disciplines :
Geriatrics
Author, co-author :
Kanis, John A ; Centre for Metabolic Bone Diseases, University of Sheffield, Sheffield, UK. w.j.Pontefract@sheffield.ac.uk
Johansson, Helena; Centre for Metabolic Bone Diseases, University of Sheffield, Sheffield, UK ; Sahlgrenska Osteoporosis Centre, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
McCloskey, Eugene V ; Centre for Metabolic Bone Diseases, University of Sheffield, Sheffield, UK ; Versus Arthritis Centre for Integrated Research in Musculoskeletal Ageing, Mellanby Centre for Musculoskeletal Research, Division of Clinical Medicine, School of Medicine & Population Health, University of Sheffield, Sheffield, UK
Liu, Enwu; South Australian Health and Medical Research Institute (SAHMRI), Adelaide, Australia
Schini, Marian; Division of Clinical Medicine, School of Medicine and Population Health, University of Sheffield, Sheffield, UK
Vandenput, Liesbeth ; Sahlgrenska Osteoporosis Centre, University of Gothenburg, Gothenburg, Sweden
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, Rafael ; Department of Medicine, Autonomous University of Barcelona, Barcelona, Spain ; Docencia Atenció Primària, Institut Català de La Salut, Metropolitana Nord, Barcelona, Spain ; GROIMAP/GROICAP (Research Groups), Unitat de Suport a La Recerca de Girona, Institut Universitari d'Investigació en Atenció Primària Jordi Gol, Girona, Spain ; PRECIOSA-Fundación Para La Investigación, Barberà del Vallés, Barcelona, Spain
Beaudart, Charlotte; 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
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, PA, USA
Center, Jacqueline R ; 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
Chapurlat, Roland; INSERM UMR 1033, Hôpital Edouard Herriot, Université Claude Bernard-Lyon1, Lyon, France
Cooper, Cyrus ; 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
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, Centro Hospitalar E Universitário de 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 ; 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
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; Interdisciplinary Centre of Bone Diseases, Bone and Joint Department, Lausanne University Hospital (CHUV) & University of Lausanne, 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 ; Agency for Science Technology and Research (A*STAR), Singapore Institute for Clinical Sciences, 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, China ; Jockey Club Centre for Osteoporosis Care and Control, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, Hong Kong, China
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, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway
Larijani, Bagher; Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
Lippuner, Kurt; Department of Osteoporosis, Bern University Hospital, University of Bern, Bern, Switzerland
McGuigan, Fiona E A; Clinical and Molecular Osteoporosis Research Unit, Department of Clinical Sciences, Lund University, Lund, Sweden
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
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 Hospital, Tam Anh Research Institute, Ho Chi Minh City, Vietnam
Nordström, Anna; 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, Uppsala, Sweden
Nordström, Peter; Department of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden
O Neill, Terence W ; National Institute for Health Research Manchester Biomedical Research Centre, Manchester Academic Health Science Centre, Manchester University NHS Foundation Trust, Manchester, UK ; Centre for Epidemiology Versus Arthritis, University of Manchester, Manchester, UK
Obermayer-Pietsch, Barbara ; Department of Internal Medicine, Division of Endocrinology and Diabetology, Medical University Graz, 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
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; INSERM UMR 1033, Hôpital Edouard Herriot, University of Lyon, Lyon, France
Sund, Reijo ; Kuopio Musculoskeletal Research Unit, University of Eastern Finland, Kuopio, Finland
Swart, Karin; 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 ; INSERM UMR 1033, Hôpital Edouard Herriot, University of Lyon, 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, Location Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands ; Aging & Later Life, Amsterdam Public Health Research Institute, 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, CIBER Epidemiology and Public Health (CIBERESP), Hospital del Mar Medical Research Institute, Barcelona, Spain
Wright, Nicole C; Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL, USA
Yoshimura, Noriko; Department of Preventive Medicine for Locomotive Organ Disorders, The University of Tokyo Hospital, Tokyo, Japan
Zillikens, M Carola ; Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands
Zwart, Marta; GROIMAP/GROICAP (Research Groups), Unitat de Suport a La Recerca de Girona, Institut Universitari d'Investigació en Atenció Primària Jordi Gol, Girona, Spain ; PRECIOSA-Fundación Para La Investigación, Barberà del Vallés, Barcelona, Spain ; Health Center Can Gibert del Plà, Catalan Institute of Health, Girona, Spain ; Department of Medical Sciences, University of Girona, Girona, Spain
Harvey, Nicholas C; 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
Lorentzon, Mattias; Sahlgrenska Osteoporosis Centre, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden ; Region Västra Götaland, Geriatric Medicine, Sahlgrenska University Hospital, Mölndal, Sweden
Leslie, William D ; Department of Medicine, University of Manitoba, Winnipeg, MB, Canada
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.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.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.R. Azagra 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.NC Harvey acknowledges funding from the UK Medical Research Council [MC_PC_21003; MC_PC_21001] and the NIHR Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, UK. 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 75N92021D00001, 75N92021D00002, 75N92021D00003, 75N92021D00004, 75N92021D00005. Funding for the MrOS USA study comes from 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, and UL1 TR000128. Funding for the SOF study comes from the National Institute on Aging (NIA), and the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), supported by grants (AG05407, AR35582, AG05394, AR35584, and AR35583). Funding for the Health ABC study was from the Intramural research program at the National Institute on Aging under the following contract numbers: NO1-AG-6\u20132101, NO1-AG-6\u20132103, and NO1-AG-6\u20132106. The Longitudinal Aging Study Amsterdam is supported by a grant from the Netherlands Ministry of Health, Welfare and Sport, Directorate of Long-Term Care. Funding for the Framingham Study comes from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) R01 AR041398 and AR061445 and the National Heart, Lung, and Blood Institute Framingham Heart Study (N01-HC-25195, HHSN268201500001I). Funding for the GOS was from the Victorian Health Promotion Foundation: ID 91\u20130095. The SUPERB study was funded with grants from the Swedish Research Council, the IngaBritt and Arne Lundberg Research Foundation, and ALF-grants from the Sahlgrenska University Hospital, Gothenburg, Sweden.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.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.
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