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Effect of TNF inhibitors on bone mineral density in rheumatoid arthritis patients receiving bisphosphonate: a retrospective cohort study

  • Bone and Cartilage
  • Published:
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Abstract

We aimed to determine whether tumor necrosis factor inhibitors (TNFi) have beneficial effects on bone mineral density (BMD) in rheumatoid arthritis (RA) patients with osteoporosis receiving bisphosphonate. A total of 199 RA patients, who were newly diagnosed with osteoporosis and receiving bisphosphonate between January 2005 and March 2017, were reviewed. Changes in BMD after 1 year were compared between patients treated with and without TNFi. The inverse probability of treatment weighting (IPTW) method using the propensity score was performed to minimize confounding factors, and logistic regression analysis was applied to identify any factors associated with significant BMD improvement (≥ 3%) at the lumbar spine and femur neck. Among patients receiving bisphosphonate, 29 were exposed to TNFi, and 170 patients were not exposed. The percentage change in BMD and the proportion of significant improvements at the lumbar spine and femur neck were similar between patients treated with and without TNFi, before and after IPTW adjustment. In addition, the disease activity score 28 (DAS28) with three variables [adjusted odds ratio (OR) 0.741, 95% confidence interval (CI) 0.592–0.927, p = 0.009] and cumulative steroid dose (adjusted OR 0.639, 95% CI 0.480–0.851, p = 0.002) were inversely associated with an improvement in BMD. Conversely, TNFi use was not associated with any improvement in BMD after adjustment by IPTW using the propensity score. TNFi did not influence BMD improvement in RA patients with osteoporosis receiving bisphosphonate, suggesting that TNFi cannot be considered as a preferred therapeutic option for increasing BMD.

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References

  1. Haugeberg G, Orstavik RE, Uhlig T, Falch JA, Halse JI, Kvien TK (2002) Bone loss in patients with rheumatoid arthritis: results from a population-based cohort of 366 patients followed up for two years. Arthritis Rheum 46:1720–1728. https://doi.org/10.1002/art.10408

    Article  PubMed  Google Scholar 

  2. van Staa TP, Geusens P, Bijlsma JW, Leufkens HG, Cooper C (2006) Clinical assessment of the long-term risk of fracture in patients with rheumatoid arthritis. Arthritis Rheum 54:3104–3112. https://doi.org/10.1002/art.22117

    Article  PubMed  Google Scholar 

  3. Ammann P, Rizzoli R, Bonjour JP, Bourrin S, Meyer JM, Vassalli P, Garcia I (1997) Transgenic mice expressing soluble tumor necrosis factor-receptor are protected against bone loss caused by estrogen deficiency. J Clin Invest 99:1699–1703. https://doi.org/10.1172/JCI119333

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Kobayashi K, Takahashi N, Jimi E, Udagawa N, Takami M, Kotake S, Nakagawa N, Kinosaki M, Yamaguchi K, Shima N, Yasuda H, Morinaga T, Higashio K, Martin TJ, Suda T (2000) Tumor necrosis factor alpha stimulates osteoclast differentiation by a mechanism independent of the ODF/RANKL-RANK interaction. J Exp Med 191:275–286. https://doi.org/10.1084/jem.191.2.275

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Krieckaert CL, Nurmohamed MT, Wolbink G, Lems WF (2013) Changes in bone mineral density during long-term treatment with adalimumab in patients with rheumatoid arthritis: a cohort study. Rheumatology 52:547–553. https://doi.org/10.1093/rheumatology/kes320

    Article  CAS  PubMed  Google Scholar 

  6. 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. https://doi.org/10.1136/ard.2005.044198

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Hoff M, Kvien TK, Kalvesten J, Elden A, Haugeberg G (2009) Adalimumab therapy reduces hand bone loss in early rheumatoid arthritis: explorative analyses from the PREMIER study. Ann Rheum Dis 68:1171–1176. https://doi.org/10.1136/ard.2008.091264

    Article  CAS  PubMed  Google Scholar 

  8. 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 44:1546–1548. https://doi.org/10.1093/rheumatology/kei082

    Article  CAS  PubMed  Google Scholar 

  9. 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. https://doi.org/10.1186/ar2219

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Yasunori K, Masaaki T, Tetsuyuki N, Hayato K, Akira N (2008) Reduction of urinary levels of pyridinoline and deoxypyridinoline and serum levels of soluble receptor activator of NF-kappaB ligand by etanercept in patients with rheumatoid arthritis. Clin Rheumatol 27:1093–1101. https://doi.org/10.1007/s10067-008-0870-8

    Article  PubMed  Google Scholar 

  11. Lim MJ, Kwon SR, Joo K, Son MJ, Park SG, Park W (2014) Early effects of tumor necrosis factor inhibition on bone homeostasis after soluble tumor necrosis factor receptor use. Korean J Intern Med 29:807–813. https://doi.org/10.3904/kjim.2014.29.6.807

    Article  PubMed  PubMed Central  Google Scholar 

  12. Orsolini G, Adami G, Adami S, Viapiana O, Idolazzi L, Gatti D, Rossini M (2016) Short-term effects of TNF inhibitors on bone turnover markers and bone mineral density in rheumatoid arthritis. Calcif Tissue Int 98:580–585. https://doi.org/10.1007/s00223-016-0114-x

    Article  CAS  PubMed  Google Scholar 

  13. Reszka AA, Rodan GA (2003) Bisphosphonate mechanism of action. Curr Rheumatol Rep 5:65–74. https://doi.org/10.1007/s11926-003-0085-6

    Article  PubMed  Google Scholar 

  14. Aletaha D, Neogi T, Silman AJ, Funovits J, Felson DT, Bingham CO 3rd, Birnbaum NS, Burmester GR, Bykerk VP, Cohen MD, Combe B, Costenbader KH, Dougados M, Emery P, Ferraccioli G, Hazes JM, Hobbs K, Huizinga TW, Kavanaugh A, Kay J, Kvien TK, Laing T, Mease P, Menard HA, Moreland LW, Naden RL, Pincus T, Smolen JS, Stanislawska-Biernat E, Symmons D, Tak PP, Upchurch KS, Vencovsky J, Wolfe F, Hawker G (2010) 2010 Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League against rheumatism collaborative initiative. Arthritis Rheum 62:2569–2581. https://doi.org/10.1002/art.27584

    Article  PubMed  Google Scholar 

  15. Madsen OR (2013) Agreement between the DAS28-CRP assessed with 3 and 4 variables in patients with rheumatoid arthritis treated with biological agents in the daily clinic. J Rheumatol 40:379–385. https://doi.org/10.3899/jrheum.120594

    Article  CAS  PubMed  Google Scholar 

  16. Austin PC (2011) An introduction to propensity score methods for reducing the effects of confounding in observational studies. Multivar Behav Res 46:399–424. https://doi.org/10.1080/00273171.2011.568786

    Article  Google Scholar 

  17. Stuart EA, Lee BK, Leacy FP (2013) Prognostic score-based balance measures can be a useful diagnostic for propensity score methods in comparative effectiveness research. J Clin Epidemiol 66:S84.e1–S90.e1. https://doi.org/10.1016/j.jclinepi.2013.01.013

    Article  Google Scholar 

  18. Tada M, Inui K, Sugioka Y, Mamoto K, Okano T, Anno S, Koike T (2017) Use of bisphosphonate might be important to improve bone mineral density in patients with rheumatoid arthritis even under tight control: the TOMORROW study. Rheumatol Int 37:999–1005. https://doi.org/10.1007/s00296-017-3720-7

    Article  CAS  PubMed  Google Scholar 

  19. Lems WF, Lodder MC, Lips P, Bijlsma JW, Geusens P, Schrameijer N, van de Ven CM, Dijkmans BA (2006) Positive effect of alendronate on bone mineral density and markers of bone turnover in patients with rheumatoid arthritis on chronic treatment with low-dose prednisone: a randomized, double-blind, placebo-controlled trial. Osteoporos Int 17:716–723. https://doi.org/10.1007/s00198-005-0037-2

    Article  CAS  PubMed  Google Scholar 

  20. Cortet B, Guyot MH, Solau E, Pigny P, Dumoulin F, Flipo RM, Marchandise X, Delcambre B (2000) Factors influencing bone loss in rheumatoid arthritis: a longitudinal study. Clin Exp Rheumatol 18:683–690

    CAS  PubMed  Google Scholar 

  21. O’Brien CA, Jia D, Plotkin LI, Bellido T, Powers CC, Stewart SA, Manolagas SC, Weinstein RS (2004) Glucocorticoids act directly on osteoblasts and osteocytes to induce their apoptosis and reduce bone formation and strength. Endocrinology 145:1835–1841. https://doi.org/10.1210/en.2003-0990

    Article  CAS  PubMed  Google Scholar 

  22. Feng Z, Zeng S, Wang Y, Zheng Z, Chen Z (2013) Bisphosphonates for the prevention and treatment of osteoporosis in patients with rheumatic diseases: a systematic review and meta-analysis. PLoS One 8:e80890. https://doi.org/10.1371/journal.pone.0080890

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Okano T, Koike T, Tada M, Sugioka Y, Mamoto K, Wakitani S, Nakamura H (2014) The limited effects of anti-tumor necrosis factor blockade on bone health in patients with rheumatoid arthritis under the use of glucocorticoid. J Bone Miner Metab 32:593–600. https://doi.org/10.1007/s00774-013-0535-9

    Article  CAS  PubMed  Google Scholar 

  24. Tawaratsumida H, Setoguchi T, Arishima Y, Ohtsubo H, Akimoto M, Ishidou Y, Nagano S, Taketomi E, Sunahara N, Komiya S (2017) Risk factors for bone loss in patients with rheumatoid arthritis treated with biologic disease-modifying anti-rheumatic drugs. BMC Res Notes 10:765. https://doi.org/10.1186/s13104-017-3086-7

    Article  PubMed  PubMed Central  Google Scholar 

  25. Maricic M, Deal C, Dore R, Laster A (2018) 2017 American college of rheumatology guideline for the prevention and treatment of glucocorticoid-induced osteoporosis: comment on the article by Buckley et al. Arthritis Care Res (Hoboken) 70:949–950. https://doi.org/10.1002/acr.23424

    Article  Google Scholar 

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Acknowledgements

The authors would like to thank Enago (http://www.enago.co.kr) for their language editing and we also thank Dr. Min Kyu Han (Departments of Clinical Epidemiology, Biostatistics, Asan Medical Center) for providing statistical support.

Funding

The research did not receive any specific Grant from funding agencies in the public, commercial, or not-for-profit sectors.

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Author notes

  1. Jung Sun Lee and Doo-Ho Lim have contributed equally to this study.

Authors and Affiliations

  1. Division of Rheumatology, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 138-736, Korea

    Jung Sun Lee, Yong-Gil Kim, Chang-Keun Lee, Bin Yoo & Seokchan Hong

  2. Division of Rheumatology, Department of Internal Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea

    Doo-Ho Lim

  3. Department of Biomedical Informatics, Asan Medical Center, Seoul, Korea

    Ji Seon Oh

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  1. Jung Sun Lee
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  4. Yong-Gil Kim
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  5. Chang-Keun Lee
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  6. Bin Yoo
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Contributions

Conceptualization and design of study: DHL, BY, and SH. Data collection: JSL and DHL. Statistical analysis: JSL and DHL. Data interpretation: JSO, YGK, CKL, BY, and SH. Manuscript preparation: JSL, DHL, and SH. Manuscript revision: JSL, YGK, CKL, BY, and SH. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

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Correspondence to Seokchan Hong.

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The authors declare no conflict of interest.

Ethical approval

This study complied with the recommendations of the Declaration of Helsinki and was approved by the Institutional Review Board of the Asan Medical Center (2018-08-08/Approval number 2018-0946).

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Lee, J.S., Lim, DH., Oh, J.S. et al. Effect of TNF inhibitors on bone mineral density in rheumatoid arthritis patients receiving bisphosphonate: a retrospective cohort study. Rheumatol Int 40, 481–487 (2020). https://doi.org/10.1007/s00296-019-04418-1

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  • DOI: https://doi.org/10.1007/s00296-019-04418-1

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