Use of bisphosphonate might be important to improve bone mineral density in patients with rheumatoid arthritis even under tight control: the TOMORROW study
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Although patients with rheumatoid arthritis (RA) are prone to osteoporosis, tight control of disease activity might have a positive effect on bone metabolism. We aimed to determine whether bisphosphonate use is still important to improve bone mineral density (BMD) in RA patients whose disease activity was tightly controlled and the dose of glucocorticoid was reduced. This study was a sub-analysis of the 10-year prospective cohort TOtal Management Of Risk factors in Rheumatoid arthritis patients to lOWer morbidity and mortality: the TOMORROW which started from 2010. We compared BMD between 192 patients with RA and age- and sex-matched volunteers between 2010 and 2013 using dual-energy X-ray absorptiometry (DXA) in whole body mode. We then determined ratios of changes in BMD (%ΔBMD) to assess factors influencing increases in BMD among the patients using multivariate logistic regression analysis. The BMD was significantly lower in the patients than in the controls at all sites surveyed during 2010 and 2013. The %ΔBMD of the total spine was significantly higher among the patients treated with, than without bisphosphonate (6.2 vs. 1.8%, P = 0.0001). Multivariate logistic regression analysis revealed that use of bisphosphonate was a significant factor contributing to BMD increase (odds ratio 2.13; 95% confidence interval, 1.03–4.38, P = 0.041). Meanwhile, use of biologic agents, reducing glucocorticoid dose, and control of disease activity were not significant factors for gain of BMD. The BMD was lower among patients with RA than non-RA controls. Use of bisphosphonate significantly increased the BMD of the spine in patients over a period of 3 years and was important for maintaining the BMD among patients with RA under the control of inflammation and disease activity.
KeywordsCohort Fragile fracture Osteoporosis Inflammatory disease Dual-energy X-ray absorptiometry
We thank Atsuko Kamiyama, Tomoko Nakatsuka and the Center for Drug and Food Clinical Evaluation, Department of Radiology and Department of Central Clinical Laboratory in Osaka City University Hospital for serving as research coordinators in terms of recruiting participants, collecting data and managing the quality of the data. We greatly appreciate the cooperation of the patients with RA and the healthy volunteers who participated in this study.
Author contribution statement
Study design: M.T. and T.K., Study implementation: T.K., Data collection: T.O., Y.S., S.A, and K.M., Data analysis: M.T. and T.K., Data interpretation: M.T., T.K., and K.I., Drafting the manuscript: M.T., T.K., and K.I., Approving the final version of the manuscript: all authors.
Compliance with ethical standards
Conflict of interest
Dr. Koike has received grant fees, research fees, consulting fees, or other remuneration from AbbVie, Astellas Pharma Inc., Bristol-Myers Squibb, Chugai Pharmaceutical, Eisai, Janssen, Lilly, Mitsubishi Tanabe Pharma Corporation, MSD, Ono Pharmaceutical, Pfizer, Roche, Takeda Pharmaceutical, Teijin Pharma, and UCB. None of the other authors has any conflict of interest to disclose.
The Ethics Committee at Osaka City University approved the study protocol. We obtained written informed consent from all patients and volunteers to participate in this study in accordance with the Declaration of Helsinki.
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