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Rheumatoid Arthritis and Subsequent Fracture Risk: An Individual Person Meta-Analysis to Update Frax Publisher Pubmed



Kanis JA1 ; Johansson H1, 2 ; Mccloskey EV1, 3 ; Liu E4 ; Schini M5 ; Vandenput L6 ; Akesson KE7, 8 ; Anderson FA9 ; Azagra R10, 11, 12, 13 ; Bager CL14 ; Beaudart C15, 16 ; Bischoffferrari HA17, 18 ; Biver E19 ; Bruyere O20 Show All Authors
Authors
  1. Kanis JA1
  2. Johansson H1, 2
  3. Mccloskey EV1, 3
  4. Liu E4
  5. Schini M5
  6. Vandenput L6
  7. Akesson KE7, 8
  8. Anderson FA9
  9. Azagra R10, 11, 12, 13
  10. Bager CL14
  11. Beaudart C15, 16
  12. Bischoffferrari HA17, 18
  13. Biver E19
  14. Bruyere O20
  15. Cauley JA21
  16. Center JR22, 23
  17. Chapurlat R24
  18. Christiansen C14
  19. Cooper C25, 26, 27
  20. Crandall CJ28
  21. Cummings SR29
  22. Da Silva JAP30, 31
  23. Dawsonhughes B32
  24. Diezperez A33
  25. Dufour AB34, 35
  26. Eisman JA22, 23, 36
  27. Elders PJM37
  28. Ferrari S19
  29. Fujita Y38
  30. Fujiwara S39
  31. Gluer CC40
  32. Goldshtein I41, 42
  33. Goltzman D43
  34. Gudnason V44, 45
  35. Hall J46
  36. Hans D47
  37. Hoff M48, 49
  38. Hollick RJ50
  39. Huisman M51, 52
  40. Iki M53
  41. Ishshalom S54
  42. Jones G55
  43. Karlsson MK7, 56
  44. Khosla S57
  45. Kiel DP34, 35
  46. Koh WP58, 59
  47. Koromani F60, 61
  48. Kotowicz MA62, 63, 64
  49. Kroger H65, 66
  50. Kwok T67, 68
  51. Lamy O69, 70
  52. Langhammer A71
  53. Larijani B72
  54. Lippuner K73
  55. Mcguigan FEA7
  56. Mellstrom D74, 75
  57. Merlijn T37
  58. Nguyen TV76, 77, 78
  59. Nordstrom A79, 80, 81
  60. Nordstrom P82
  61. Oneill TW83, 84
  62. Obermayerpietsch B85
  63. Ohlsson C2, 86
  64. Orwoll ES87
  65. Pasco JA62, 63, 64, 88
  66. Rivadeneira F60
  67. Schott AM89
  68. Shiroma EJ90
  69. Siggeirsdottir K44, 91
  70. Simonsick EM92
  71. Sornayrendu E93
  72. Sund R66
  73. Swart K94, 95
  74. Szulc P93
  75. Tamaki J96
  76. Torgerson DJ97
  77. Van Schoor NM98, 99
  78. Van Staa TP100
  79. Vila J101
  80. Wright NC102
  81. Yoshimura N103
  82. Zillikens MC60
  83. Zwart M12, 13, 104, 105
  84. Harvey NC25, 26
  85. Lorentzon M2, 106
  86. Leslie WD107
Show Affiliations
Authors Affiliations
  1. 1. Centre for Metabolic Bone Diseases, University of Sheffield, Sheffield, United Kingdom
  2. 2. Sahlgrenska Osteoporosis Centre, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
  3. 3. 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, United Kingdom
  4. 4. South Australian Health and Medical Research Institute (SAHMRI), Adelaide, Australia
  5. 5. Division of Clinical Medicine, School of Medicine and Population Health, University of Sheffield, Sheffield, United Kingdom
  6. 6. Sahlgrenska Osteoporosis Centre, University of Gothenburg, Gothenburg, Sweden
  7. 7. Clinical and Molecular Osteoporosis Research Unit, Department of Clinical Sciences, Lund University, Lund, Sweden
  8. 8. Department of Orthopedics, Skane University Hospital, Malmo, Sweden
  9. 9. GLOW Coordinating Center, Center for Outcomes Research, University of Massachusetts Medical School, Worcester, MA, United States
  10. 10. Department of Medicine, Autonomous University of Barcelona, Barcelona, Spain
  11. 11. Docencia Atencio Primaria, Institut Catala de La Salut, Metropolitana Nord, Barcelona, Spain
  12. 12. GROIMAP/GROICAP (Research Groups), Unitat de Suport a La Recerca de Girona, Institut Universitari d’Investigacio en Atencio Primaria Jordi Gol, Girona, Spain
  13. 13. PRECIOSA-Fundacion Para La Investigacion, Barbera del Valles, Barcelona, Spain
  14. 14. Nordic Bioscience A/S, Herlev, Denmark
  15. 15. WHO Collaborating Centre for Public Health Aspects of Musculoskeletal Health and Aging, Division of Public Health, Epidemiology and Health Economics, University of Liege, Liege, Belgium
  16. 16. Department of Health Services Research, University of Maastricht, Maastricht, Netherlands
  17. 17. Department of Aging Medicine and Aging Research, University Hospital Zurich and University of Zurich, Zurich, Switzerland
  18. 18. Centre On Aging and Mobility, University of Zurich and City Hospital, Zurich, Switzerland
  19. 19. Division of Bone Diseases, Department of Medicine, Geneva University Hospitals and Faculty of Medicine, University of Geneva, Geneva, Switzerland
  20. 20. Research Unit in Public Health, Epidemiology and Health Economics, University of Liege, Liege, Belgium
  21. 21. Department of Epidemiology, School of Public Health, University of Pittsburgh, Pittsburgh, PA, United States
  22. 22. Skeletal Diseases Program, Garvan Institute of Medical Research, Sydney, NSW, Australia
  23. 23. St Vincent’s Clinical School, School of Medicine and Health, University of New South Wales Sydney, Sydney, NSW, Australia
  24. 24. INSERM UMR 1033, Hopital Edouard Herriot, Universite Claude Bernard-Lyon1, Lyon, France
  25. 25. MRC Lifecourse Epidemiology Centre, University of Southampton, Southampton, United Kingdom
  26. 26. NIHR Southampton Biomedical Research Centre, University of Southampton and University Hospitals Southampton NHS Foundation Trust, Southampton, United Kingdom
  27. 27. NIHR Oxford Biomedical Research Unit, University of Oxford, Oxford, United Kingdom
  28. 28. Division of General Internal Medicine and Health Services Research, David Geffen School of Medicine, University of California, Los Angeles, CA, United States
  29. 29. San Francisco Coordinating Center, California Pacific Medical Center Research Institute, San Francisco, CA, United States
  30. 30. Coimbra Institute for Clinical and Biomedical Research, Faculty of Medicine, University of Coimbra, Coimbra, Portugal
  31. 31. Rheumatology Department, Centro Hospitalar E Universitario de Coimbra, Coimbra, Portugal
  32. 32. Bone Metabolism Laboratory, Jean Mayer US Department of Agriculture Human Nutrition Research Center On Aging, Tufts University, Boston, MA, United States
  33. 33. Department of Internal Medicine, Hospital del Mar and CIBERFES, Autonomous University of Barcelona, Barcelona, Spain
  34. 34. Marcus Institute for Aging Research, Hebrew SeniorLife, Boston, MA, United States
  35. 35. Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States
  36. 36. School of Medicine Sydney, University of Notre Dame Australia, Sydney, NSW, Australia
  37. 37. Department of General Practice, Amsterdam UMC, Location AMC, Amsterdam Public Health Research Institute, Amsterdam, Netherlands
  38. 38. Department of Hygiene and Public Health, Faculty of Medicine, Kansai Medical University, Osaka, Japan
  39. 39. Department of Pharmacy, Yasuda Women’s University, Hiroshima, Japan
  40. 40. Section Biomedical Imaging, Molecular Imaging North Competence Center, Department of Radiology and Neuroradiology, University Medical Center Schleswig-Holstein Kiel, Kiel University, Kiel, Germany
  41. 41. Maccabitech Institute of Research and Innovation, Maccabi Healthcare Services, Tel Aviv, Israel
  42. 42. Department of Epidemiology and Preventive Medicine, School of Public Health, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
  43. 43. Department of Medicine, McGill University and McGill University Health Centre, Montreal, Canada
  44. 44. Icelandic Heart Association, Kopavogur, Iceland
  45. 45. University of Iceland, Reykjavik, Iceland
  46. 46. MRC Centre for Reproductive Health, University of Edinburgh, Edinburgh, United Kingdom
  47. 47. Interdisciplinary Centre of Bone Diseases, Bone and Joint Department, Lausanne University Hospital (CHUV) & University of Lausanne, Lausanne, Switzerland
  48. 48. Department of Neuromedicine and Movement Science, Norwegian University of Science and Technology, Trondheim, Norway
  49. 49. Department of Rheumatology, St Olavs Hospital, Trondheim, Norway
  50. 50. Aberdeen Centre for Arthritis and Musculoskeletal Health, Epidemiology Group, University of Aberdeen, Aberdeen, United Kingdom
  51. 51. Department of Epidemiology and Data Science, Amsterdam Public Health Research Institute, VU University Medical Center, Amsterdam, Netherlands
  52. 52. Department of Sociology, VU University, Amsterdam, Netherlands
  53. 53. Department of Public Health, Faculty of Medicine, Kindai University, Osaka, Japan
  54. 54. Endocrine Clinic, Elisha Hospital, Haifa, Israel
  55. 55. Menzies Institute for Medical Research, University of Tasmania, Hobart, Australia
  56. 56. Department of Orthopaedics, Skane University Hospital, Malmo, Sweden
  57. 57. Robert and Arlene Kogod Center On Aging and Division of Endocrinology, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, MN, United States
  58. 58. Healthy Longevity Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
  59. 59. Agency for Science Technology and Research (A*STAR), Singapore Institute for Clinical Sciences, Singapore, Singapore
  60. 60. Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, Netherlands
  61. 61. Department of Radiology and Nuclear Medicine, Erasmus University Medical Center, Rotterdam, Netherlands
  62. 62. IMPACT (Institute for Mental and Physical Health and Clinical Translation), Deakin University, Geelong, VIC, Australia
  63. 63. Barwon Health, Geelong, VIC, Australia
  64. 64. Department of Medicine - Western Health, The University of Melbourne, St Albans, Victoria, Australia
  65. 65. Department of Orthopedics and Traumatology, Kuopio University Hospital, Kuopio, Finland
  66. 66. Kuopio Musculoskeletal Research Unit, University of Eastern Finland, Kuopio, Finland
  67. 67. Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong
  68. 68. Jockey Club Centre for Osteoporosis Care and Control, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong
  69. 69. Centre of Bone Diseases, Lausanne University Hospital, Lausanne, Switzerland
  70. 70. Service of Internal Medicine, Lausanne University Hospital, Lausanne, Switzerland
  71. 71. HUNT Research Centre, Department of Public Health and Nursing, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway
  72. 72. Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
  73. 73. Department of Osteoporosis, Bern University Hospital, University of Bern, Bern, Switzerland
  74. 74. Geriatric Medicine, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
  75. 75. Geriatric Medicine, Sahlgrenska University Hospital Molndal, Molndal, Sweden
  76. 76. School of Biomedical Engineering, University of Technology Sydney, Sydney, Australia
  77. 77. School of Population Health, UNSW Medicine, UNSW Sydney, Kensington, Australia
  78. 78. Tam Anh Hospital, Tam Anh Research Institute, Ho Chi Minh City, Viet Nam
  79. 79. School of Sport Sciences, UiT The Arctic University of Norway, Tromso, Norway
  80. 80. Department of Health Sciences, Swedish Winter Sports Research Centre, Mid Sweden University, Ostersund, Sweden
  81. 81. Department of Medical Sciences, Uppsala University, Uppsala, Sweden
  82. 82. Department of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden
  83. 83. National Institute for Health Research Manchester Biomedical Research Centre, Manchester Academic Health Science Centre, Manchester University NHS Foundation Trust, Manchester, United Kingdom
  84. 84. Centre for Epidemiology Versus Arthritis, University of Manchester, Manchester, United Kingdom
  85. 85. Department of Internal Medicine, Division of Endocrinology and Diabetology, Medical University Graz, Graz, Austria
  86. 86. Department of Drug Treatment, Sahlgrenska University Hospital, Region Vastra Gotaland, Gothenburg, Sweden
  87. 87. Department of Medicine, Oregon Health and Science University, Portland, OR, United States
  88. 88. Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia
  89. 89. Universite Claude Bernard Lyon 1, U INSERM 1290 RESHAPE, Lyon, France
  90. 90. Laboratory of Epidemiology and Population Sciences, National Institute On Aging, Baltimore, MD, United States
  91. 91. Janus Rehabilitation, Reykjavik, Iceland
  92. 92. Translational Gerontology Branch, National Institute On Aging Intramural Research Program, Baltimore, MD, United States
  93. 93. INSERM UMR 1033, Hopital Edouard Herriot, University of Lyon, Lyon, France
  94. 94. Department of General Practice, Amsterdam Public Health Research Institute, Amsterdam UMC, Location VUmc, Amsterdam, Netherlands
  95. 95. PHARMO Institute for Drug Outcomes Research, Utrecht, Netherlands
  96. 96. Department of Hygiene and Public Health, Faculty of Medicine, Educational Foundation of Osaka Medical and Pharmaceutical University, Osaka, Japan
  97. 97. York Trials Unit, Department of Health Sciences, University of York, York, United Kingdom
  98. 98. Department of Epidemiology and Data Science, Location Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, Netherlands
  99. 99. Aging & Later Life, Amsterdam Public Health Research Institute, Amsterdam, Netherlands
  100. 100. Centre for Health Informatics, Faculty of Biology, Medicine and Health, School of Health Sciences, University of Manchester, Manchester, United Kingdom
  101. 101. Statistics Support Unit, CIBER Epidemiology and Public Health (CIBERESP), Hospital del Mar Medical Research Institute, Barcelona, Spain
  102. 102. Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL, United States
  103. 103. Department of Preventive Medicine for Locomotive Organ Disorders, The University of Tokyo Hospital, Tokyo, Japan
  104. 104. Health Center Can Gibert del Pla, Catalan Institute of Health, Girona, Spain
  105. 105. Department of Medical Sciences, University of Girona, Girona, Spain
  106. 106. Region Vastra Gotaland, Geriatric Medicine, Sahlgrenska University Hospital, Molndal, Sweden
  107. 107. Department of Medicine, University of Manitoba, Winnipeg, MB, Canada

Source: Osteoporosis International Published:2025


Abstract

Summary: 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. © International Osteoporosis Foundation and Bone Health and Osteoporosis Foundation 2025.