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

Summary: RA fracture risk? Meta-analysis shows RA ups fracture HR, especially hip. Research suggests FRAX update for better prediction. Bone safety? #RheumatoidArthritis #FractureRisk

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

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.
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