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

  • Jung Sun Lee
  • Doo-Ho Lim
  • Ji Seon Oh
  • Yong-Gil Kim
  • Chang-Keun Lee
  • Bin Yoo
  • Seokchan HongEmail author
Bone and Cartilage


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.


Osteoporosis Rheumatoid arthritis Diphosphonate Tumor necrosis factor Antibodies Monoclonal 



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

Authors’ 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.


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

Compliance with ethical standards

Conflict of interest

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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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Division of Rheumatology, Department of Internal Medicine, Asan Medical CenterUniversity of Ulsan College of MedicineSeoulKorea
  2. 2.Division of Rheumatology, Department of Internal Medicine, Ulsan University HospitalUniversity of Ulsan College of MedicineUlsanKorea
  3. 3.Department of Biomedical InformaticsAsan Medical CenterSeoulKorea

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