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Biologic disease-modifying anti-rheumatic drugs and the risk of non-vertebral osteoporotic fractures in patients with rheumatoid arthritis aged 50 years and over

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Abstract

Summary

Prevention of bone mineral density loss in rheumatoid arthritis (RA) has been associated with use of biologic disease-modifying anti-rheumatic drugs (DMARDs). However, in this study, we could not demonstrate a reduction in the risk of non-vertebral fractures. Additional research is required to clarify the impact of biologic DMARDs on fracture risk in RA.

Introduction

Small studies have suggested biologic DMARDs preserve bone mineral density at 6–12 months. Our objective was to determine the association between biologic DMARD use and the risk of non-vertebral osteoporotic fractures in RA subjects aged ≥50 years.

Methods

A nested case–control study was conducted using Quebec physician billing and hospital discharge data. RA subjects were identified from International Classification of Disease-9/10 codes in billing and hospitalisation data and followed from cohort entry until the earliest of non-vertebral osteoporotic fracture, death, or end of study period. Controls were matched to cases (4:1 ratio) on age, sex, and date of cohort entry. Biologic DMARD exposure was defined as being on treatment for ≥180 days pre-fracture (index). Conditional logistic regression was used, adjusting for indicators of RA severity, comorbidity, drugs influencing fracture risk, and measures of health care utilisation.

Results

Over the study period, 1,515 cases were identified (6,023 controls). The most frequent fracture site was hip/femur (42.3 %). In total, 172 subjects (49 cases and 123 controls) were exposed to biologic DMARDs. The median duration of exposure was 735 (interquartile range (IQR), 564) and 645 (IQR, 903) days in cases and controls, respectively. We were unable to demonstrate an association between biologic DMARDs and fracture risk (odds ratio, 1.03; 95 % confidence interval, 0.42–2.53). RA duration significantly increased the fracture risk.

Conclusions

Despite the positive impact of biologic DMARDs on bone remodelling observed in small studies, we were unable to demonstrate a reduction in the risk of non-vertebral osteoporotic fractures in older adults with RA.

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References

  1. Redlich K, Smolen JS (2012) Inflammatory bone loss: pathogenesis and therapeutic intervention. Nat Rev Drug Discov 11:234–250

    Article  PubMed  CAS  Google Scholar 

  2. Vosse D, de Vlam K (2009) Osteoporosis in rheumatoid arthritis and ankylosing spondylitis. Clin Exp Rheumatol 27:S62–S67

    PubMed  CAS  Google Scholar 

  3. Weiss RJ, Wick MC, Ackermann PW, Montgomery SM (2010) Increased fracture risk in patients with rheumatic disorders and other inflammatory diseases—a case–control study with 53,108 patients with fracture. J Rheumatol 37:2247–2250

    Article  PubMed  Google Scholar 

  4. Wright NC, Lisse JR, Walitt BT, Eaton CB, Chen Z (2011) Arthritis increases the risk for fractures—results from the Women's Health Initiative. J Rheumatol 38:1680–1688

    Article  PubMed  Google Scholar 

  5. Michaud K, Wolfe F (2007) Comorbidities in rheumatoid arthritis. Best Pract Res Clin Rheumatol 21:885–906

    Article  PubMed  Google Scholar 

  6. Bykerk VP, Akhavan P, Hazlewood GS, Schieir O, Dooley A, Haraoui B, Khraishi M, Leclercq SA, Legare J, Mosher DP, Pencharz J, Pope JE, Thomson J, Thorne C, Zummer M, Bombardier C (2012) Canadian Rheumatology Association recommendations for pharmacological management of rheumatoid arthritis with traditional and biologic disease-modifying antirheumatic drugs. J Rheumatol 39:1559–1582

    Article  PubMed  CAS  Google Scholar 

  7. Chopin F, Garnero P, le Henanff A, Debiais F, Daragon A, Roux C, Sany J, Wendling D, Zarnitsky C, Ravaud P, Thomas T (2008) Long-term effects of infliximab on bone and cartilage turnover markers in patients with rheumatoid arthritis. Ann Rheum Dis 67:353–357

    Article  PubMed  CAS  Google Scholar 

  8. Eekman DA, Vis M, Bultink IE, Kuik DJ, Voskuyl AE, Dijkmans BA, Lems WF (2011) Stable bone mineral density in lumbar spine and hip in contrast to bone loss in the hands during long-term treatment with infliximab in patients with rheumatoid arthritis. Ann Rheum Dis 70:389–390

    Article  PubMed  Google Scholar 

  9. Guler-Yuksel M, Allaart CF, Goekoop-Ruiterman YP, de Vries-Bouwstra JK, van Groenendael JH, Mallee C, de Bois MH, Breedveld FC, Dijkmans BA, Lems WF (2009) Changes in hand and generalised bone mineral density in patients with recent-onset rheumatoid arthritis. Ann Rheum Dis 68:330–336

    Article  PubMed  CAS  Google Scholar 

  10. Haugeberg G, Conaghan PG, Quinn M, Emery P (2009) Bone loss in patients with active early rheumatoid arthritis: infliximab and methotrexate compared with methotrexate treatment alone. Explorative analysis from a 12-month randomised, double-blind, placebo-controlled study. Ann Rheum Dis 68:1898–1901

    Article  PubMed  CAS  Google Scholar 

  11. Hoff M, Kvien TK, Kalvesten J, Elden A, Kavanaugh A, Haugeberg G (2011) Adalimumab reduces hand bone loss in rheumatoid arthritis independent of clinical response: subanalysis of the PREMIER study. BMC Musculoskelet Disord 12:54

    Article  PubMed  CAS  Google Scholar 

  12. Marotte H, Pallot-Prades B, Grange L, Gaudin P, Alexandre C, Miossec P (2007) A 1-year case–control study in patients with rheumatoid arthritis indicates prevention of loss of bone mineral density in both responders and nonresponders to infliximab. Arthritis Res Ther 9:R61

    Article  PubMed  Google Scholar 

  13. Serelis J, Kontogianni MD, Katsiougiannis S, Bletsa M, Tektonidou MG, Skopouli FN (2008) Effect of anti-TNF treatment on body composition and serum adiponectin levels of women with rheumatoid arthritis. Clin Rheumatol 27:795–797

    Article  PubMed  Google Scholar 

  14. Vis M, Havaardsholm EA, Haugeberg G, Uhlig T, Voskuyl AE, van de Stadt RJ, Dijkmans BA, Woolf AD, Kvien TK, Lems WF (2006) Evaluation of bone mineral density, bone metabolism, osteoprotegerin and receptor activator of the NFkappaB ligand serum levels during treatment with infliximab in patients with rheumatoid arthritis. Ann Rheum Dis 65:1495–1499

    Article  PubMed  CAS  Google Scholar 

  15. Wijbrandts CA, Klaasen R, Dijkgraaf MG, Gerlag DM, van Eck-Smit BL, Tak PP (2009) Bone mineral density in rheumatoid arthritis patients 1 year after adalimumab therapy: arrest of bone loss. Ann Rheum Dis 68:373–376

    Article  PubMed  CAS  Google Scholar 

  16. Lange U, Teichmann J, Muller-Ladner U, Strunk J (2005) Increase in bone mineral density of patients with rheumatoid arthritis treated with anti-TNF-alpha antibody: a prospective open-label pilot study. Rheumatology (Oxford) 44:1546–1548

    Article  CAS  Google Scholar 

  17. Seriolo B, Paolino S, Sulli A, Ferretti V, Cutolo M (2006) Bone metabolism changes during anti-TNF-alpha therapy in patients with active rheumatoid arthritis. Ann N Y Acad Sci 1069:420–427

    Article  PubMed  CAS  Google Scholar 

  18. RAMQ (2012). Régie de l'assurance maladie du Québec. Data and statistics (updated 2012). Available from http://www.ramq.gouv.qc.ca/en/data-statistics/Pages/data-statistics.aspx. Accessed 1 Aug 2012

  19. Tamblyn R, Lavoie G, Petrella L, Monette J (1995) The use of prescription claims databases in pharmacoepidemiological research: the accuracy and comprehensiveness of the prescription claims database in Quebec. J Clin Epidemiol 48:999–1009

    Article  PubMed  CAS  Google Scholar 

  20. Jean S, Candas B, Belzile E, Morin S, Bessette L, Dodin S, Brown JP (2012) Algorithms can be used to identify fragility fracture cases in physician-claims databases. Osteoporos Int 23:483–501

    Article  PubMed  CAS  Google Scholar 

  21. Giangregorio LM, Leslie WD (2010) Time since prior fracture is a risk modifier for 10-year osteoporotic fractures. J Bone Miner Res 25:1400–1405

    Article  PubMed  Google Scholar 

  22. Deyo RA, Cherkin DC, Ciol MA (1992) Adapting a clinical comorbidity index for use with ICD-9-CM administrative databases. J Clin Epidemiol 45:613–619

    Article  PubMed  CAS  Google Scholar 

  23. Leslie WD, Lix LM, Yogendran MS (2011) Validation of a case definition for osteoporosis disease surveillance. Osteoporos Int 22:37–46

    Article  PubMed  CAS  Google Scholar 

  24. Woolcott JC, Richardson KJ, Wiens MO, Patel B, Marin J, Khan KM, Marra CA (2009) Meta-analysis of the impact of 9 medication classes on falls in elderly persons. Arch Intern Med 169:1952–1960

    Article  PubMed  Google Scholar 

  25. Nikitovic M, Wodchis WP, Krahn MD, Cadarette SM (2013) Direct health-care costs attributed to hip fractures among seniors: a matched cohort study. Osteoporos Int 24:659–669

    Article  PubMed  CAS  Google Scholar 

  26. Hopkins RB, Tarride JE, Leslie WD, Metge C, Lix LM, Morin S, Finlayson G, Azimaee M, Pullenayegum E, Goeree R, Adachi JD, Papaioannou A, Thabane L (2013) Estimating the excess costs for patients with incident fractures, prevalent fractures, and nonfracture osteoporosis. Osteoporos Int 24:581–593

    Article  PubMed  CAS  Google Scholar 

  27. Bessette L, Jean S, Lapointe-Garant MP, Belzile EL, Davison KS, Ste-Marie LG, Brown JP (2012) Direct medical costs attributable to peripheral fractures in Canadian post-menopausal women. Osteoporos Int 23:1757–1768

    Article  PubMed  CAS  Google Scholar 

  28. Cheng CK, McDonald-Blumer H, Boire G, Pope JE, Haraoui B, Hitchon CA, Thorne C, Sun Y, Bykerk VP (2010) Care gap in patients with early inflammatory arthritis with a high fracture risk identified using FRAX((R)). J Rheumatol 37:2221–2225

    Article  PubMed  Google Scholar 

  29. Solomon DH, Katz JN, Cabral D, Patrick AR, Bukowski JF, Coblyn JS (2006) Osteoporosis management in patients with rheumatoid arthritis: evidence for improvement. Arthritis Rheum 55:873–877

    Article  PubMed  CAS  Google Scholar 

  30. Kim SY, Schneeweiss S, Liu J, Daniel GW, Chang CL, Garneau K, Solomon DH (2010) Risk of osteoporotic fracture in a large population-based cohort of patients with rheumatoid arthritis. Arthritis Res Ther 12:R154

    Article  PubMed  Google Scholar 

  31. Vis M, Haavardsholm EA, Boyesen P, Haugeberg G, Uhlig T, Hoff M, Woolf A, Dijkmans B, Lems W, Kvien TK (2011) High incidence of vertebral and non-vertebral fractures in the OSTRA cohort study: a 5-year follow-up study in postmenopausal women with rheumatoid arthritis. Osteoporos Int 22:2413–2419

    Article  PubMed  CAS  Google Scholar 

  32. Coulson KA, Reed G, Gilliam BE, Kremer JM, Pepmueller PH (2009) Factors influencing fracture risk, T score, and management of osteoporosis in patients with rheumatoid arthritis in the Consortium of Rheumatology Researchers of North America (CORRONA) registry. J Clin Rheumatol 15:155–160

    Article  PubMed  Google Scholar 

  33. Kim SY, Schneeweiss S, Liu J, Solomon DH (2012) Effects of disease-modifying antirheumatic drugs on nonvertebral fracture risk in rheumatoid arthritis: a population-based cohort study. J Bone Miner Res 27:789–796

    Article  PubMed  CAS  Google Scholar 

  34. Lacaille D, Anis AH, Guh DP, Esdaile JM (2005) Gaps in care for rheumatoid arthritis: a population study. Arthritis Rheum 53:241–248

    Article  PubMed  Google Scholar 

  35. Shipton D, Glazier RH, Guan J, Badley EM (2004) Effects of use of specialty services on disease-modifying antirheumatic drug use in the treatment of rheumatoid arthritis in an insured elderly population. Med Care 42:907–913

    Article  PubMed  Google Scholar 

  36. Widdifield J, Bernatsky S, Paterson JM, Thorne JC, Cividino A, Pope J, Gunraj N, Bombardier C (2011) Quality care in seniors with new-onset rheumatoid arthritis: a Canadian perspective. Arthritis Care Res (Hoboken ) 63:53–57

    Article  Google Scholar 

  37. Curtis JR, Mudano AS, Solomon DH, Xi J, Melton ME, Saag KG (2009) Identification and validation of vertebral compression fractures using administrative claims data. Med Care 47:69–72

    Article  PubMed  Google Scholar 

  38. Lix LM, Azimaee M, Osman BA, Caetano P, Morin S, Metge C, Goltzman D, Kreiger N, Prior J, Leslie WD (2012) Osteoporosis-related fracture case definitions for population-based administrative data. BMC Publ Health 12:301

    Article  Google Scholar 

  39. MacLean CH, Park GS, Traina SB, Liu HH, Hahn BH, Paulus HE, Kahn KL (2001) Positive predictive value (PPV) of an administrative data-based algorithm for the identification of patients with rheumatoid arthritis (RA) [abstract]. Arthritis & Rheum 44(S9):S106

    Google Scholar 

  40. Kim SY, Servi A, Polinski JM, Mogun H, Weinblatt ME, Katz JN, Solomon DH (2011) Validation of rheumatoid arthritis diagnoses in health care utilization data. Arthritis Res Ther 13:R32

    Article  PubMed  Google Scholar 

  41. Kanis JA, Johnell O, Oden A, Johansson H, McCloskey E (2008) FRAX and the assessment of fracture probability in men and women from the UK. Osteoporos Int 19:385–397

    Article  PubMed  CAS  Google Scholar 

  42. Nampei A, Hashimoto J, Koyanagi J, Ono T, Hashimoto H, Tsumaki N, Tomita T, Sugamoto K, Nishimoto N, Ochi T, Yoshikawa H (2008) Characteristics of fracture and related factors in patients with rheumatoid arthritis. Mod Rheumatol 18:170–176

    Article  PubMed  Google Scholar 

  43. Romas E, Gillespie MT (2006) Inflammation-induced bone loss: can it be prevented? Rheum Dis Clin North Am 32:759–773

    Article  PubMed  Google Scholar 

  44. Vinet E, Kuriya B, Widdifield J, Bernatsky S (2011) Rheumatoid arthritis disease severity indices in administrative databases: a systematic review. J Rheumatol 38:2318–2325

    Article  PubMed  Google Scholar 

  45. Leslie WD, Morin SN, Lix LM (2012) Rate of bone density change does not enhance fracture prediction in routine clinical practice. J Clin Endocrinol Metab 97:1211–1218

    Article  PubMed  CAS  Google Scholar 

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Conflicts of interest

No funding was received for this research. Jean-Pascal Roussy is an employee of Pfizer Canada Inc. Pfizer Canada did not provide financial support for this study and was not involved in the study design, implementation, interpretation and reporting of the results. This work is attributable to the University of Montreal where Jean-Pascal Roussy is a Ph.D. candidate and the McGill University. Dr. Louis Bessette has received research grants and consultant fees from Pfizer Canada Inc. on issues unrelated to the current study. Dr. Sasha Bernatsky has no financial interests to disclose. Dr. Elham Rahme is a research scholar funded by The Fonds de Recherche en Santé du Québec. In the past 3 years, she received grants and/or consultant fees from Merck & Co. Inc. and Pfizer Canada Inc. on issues unrelated to the current study. Dr. Jean Lachaine has received research support from Abbott Laboratories, Merck Canada Inc. and Pfizer Canada Inc. on issues unrelated to the current study.

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Authors and Affiliations

  1. Faculty of Pharmacy, University of Montreal, Pavillon Jean-Coutu, 2940 chemin de la polytechnique, Montreal, QC, Canada, H3C 3J7

    J.-P. Roussy & J. Lachaine

  2. Laval University, Centre Hospitalier Universitaire de Québec, pavillon CHUL, 2705 boulevard Laurier, Quebec, QC, Canada, G1V 4G2

    L. Bessette

  3. Division of Clinical Epidemiology, McGill University, Research Institute of the McGill University Health Centre, A6-1650 Cedar Ave, Montreal, QC, Canada, H3A 1A4

    S. Bernatsky

  4. Division of Clinical Epidemiology, McGill University, Research Institute of the McGill University Health Centre, Royal Victoria Hospital, V Building (Rm. V2.11), 687 Pine Avenue West, Montreal, QC, Canada, H3A 1A1

    E. Rahme

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  1. J.-P. Roussy
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Correspondence to E. Rahme.

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Roussy, JP., Bessette, L., Bernatsky, S. et al. Biologic disease-modifying anti-rheumatic drugs and the risk of non-vertebral osteoporotic fractures in patients with rheumatoid arthritis aged 50 years and over. Osteoporos Int 24, 2483–2492 (2013). https://doi.org/10.1007/s00198-013-2321-x

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  • DOI: https://doi.org/10.1007/s00198-013-2321-x

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