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Reducing glucocorticoid dosage improves serum osteocalcin in patients with rheumatoid arthritis—results from the TOMORROW study

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Abstract

Summary

Decreasing the daily dose of glucocorticoids improved bone metabolic marker levels in patients with rheumatoid arthritis. However, changes in disease activity did not influence bone metabolism. Bone metabolism might thus remain uncontrolled even if disease activity is under good control. Decreasing glucocorticoid dosage appears important for improving bone metabolism.

Introduction

Patients with rheumatoid arthritis (RA) develop osteoporosis more frequently than healthy individuals. Bone resorption is increased and bone formation is inhibited in patients with RA, and glucocorticoid negatively affects bone metabolism. We aimed to investigate factors influencing bone metabolic markers in patients with RA.

Methods

We started the 10-year prospective cohort Total Management of Risk Factors in Rheumatoid Arthritis Patients to Lower Morbidity and Mortality (TOMORROW) study in 2010. We compared changes in urinary cross-linked N-telopeptide of type I collagen (uNTx) and serum osteocalcin (OC), as markers of bone resorption and formation, respectively, in 202 RA patients and age- and sex-matched volunteers between 2010 and 2011. We also investigated factors influencing ΔuNTx and ΔOC in the RA group using multivariate analysis.

Results

Values of ΔuNTx were significantly lower in patients with RA than in healthy controls (−0.51 vs. 7.41 nmol bone collagen equivalents (BCE)/mmol creatinine (Cr); p = 0.0013), whereas ΔOC values were significantly higher in RA patients (0.94 vs. 0.37 ng/ml; p = 0.0065). Changes in prednisolone dosage correlated negatively with ΔOC (β = −0.229, p = 0.001), whereas changes in disease activity score, bisphosphonate therapy, and period of biologics therapy did not correlate significantly with ΔOC. No significant correlation was seen between ΔuNTx and change in prednisolone dosage.

Conclusions

Decreased glucocorticoid dosage improved bone metabolic markers in RA, but disease activity, bisphosphonate therapy, and period of biologics therapy did not influence levels of bone metabolic markers. Decreasing glucocorticoid dosage appears important for improving bone metabolic marker profiles in patients with RA.

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Acknowledgments

We wish to thank Atsuko Kamiyama, Tomoko Nakatsuka, and the Center for Drug & Food Clinical Evaluation, Department of Radiology, and Department of Central Clinical Laboratory in Osaka City University Hospital for their special efforts as research coordinators in recruiting subjects, collecting data, and managing the quality of data. We greatly appreciate the cooperation of the patients with RA and volunteers who participated in this study.

Conflicts 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. Dr. Nakamura has received research grants and/or speaking fees from Chugai Pharmaceutical, Astellas Pharma, Janssen Pharmaceutica, GlaxoSmithKline, Pfizer, Daiichi Sankyo, and Ono Pharmaceutical. Dr. Tada, Dr. Inui, Dr. Sugioka, Dr. Mamoto, and Dr. Okano do not have any conflict of interest.

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Authors and Affiliations

  1. Department of Orthopaedic Surgery, Osaka City University Medical School, 1-4-3 Asahimachi, Abeno-ku, Osaka, 545-8585, Japan

    M. Tada, K. Mamoto, T. Okano & H. Nakamura

  2. Department of Rheumatosurgery, Osaka City University Medical School, 1-4-3 Asahimachi, Abeno-ku, Osaka, 545-8585, Japan

    K. Inui

  3. Center for Senile Degenerative Disorders, Osaka City University Medical School, 1-4-3 Asahimachi, Abeno-ku, Osaka, 545-8585, Japan

    Y. Sugioka & T. Koike

  4. Search Institute for Bone and Arthritis Disease, Shirahama Foundation for Health and Welfare, Nishimurogun Shirahamacho 1447, Wakayama, 649-2211, Japan

    T. Koike

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  1. M. Tada
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  2. K. Inui
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  3. Y. Sugioka
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Correspondence to T. Koike.

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Tada, M., Inui, K., Sugioka, Y. et al. Reducing glucocorticoid dosage improves serum osteocalcin in patients with rheumatoid arthritis—results from the TOMORROW study. Osteoporos Int 27, 729–735 (2016). https://doi.org/10.1007/s00198-015-3291-y

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  • DOI: https://doi.org/10.1007/s00198-015-3291-y

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