Abstract
Summary
Bone mineral density (BMD) sometimes cannot be improved by long-term bisphosphonate (BP) therapy in osteoporosis (OP) patients with rheumatoid arthritis (RA). This study showed that BMD significantly increased after denosumab treatment in patients with long-term BP pre-treatment as much as in treatment-naïve patients. Thus, denosumab can be a strong OP treatment option for long-term BP pre-treated RA patients.
Introduction
The aim of this 24-month retrospective study was to evaluate differences in outcomes of denosumab with or without bisphosphonate (BP) pre-treatment in osteoporosis (OP) patients with rheumatoid arthritis (RA).
Methods
Patients were divided into those with (BP group, 26 cases) or without (denosumab group, 26 cases) BP pre-treatment. We measured serum BAP, TRACP-5b, and urinary NTX at baseline and every 3 months for 24 months. We also assessed bone mineral density (BMD) of the lumbar 1–4 vertebrae (L-BMD) and total hip BMD (H-BMD) at baseline and every 6 months for 24 months. MMP-3, DAS28-CRP, SDAI, and HAQ-DI were assessed at baseline and 24 months to evaluate RA state.
Results
In BP group, the percent changes of bone turnover markers decreased but were consistently higher compared with those in the denosumab group. There were significant differences of the percent changes in BAP at 9, 21, and 24 months; TRACP-5b at 9, 18, and 21 months; and urinary NTX at 3, 9, 12, 15, 18, and 21 months between the groups. The percent changes of L-BMD and H-BMD were significantly increased at 24 months in the BP pre-treated group (11.5 and 13.3%, respectively) and denosumab group (13.0 and 16.5%, respectively). There was a significant difference of the percent changes in H-BMD at 6 months between the groups. There was no significant difference in RA state between the groups.
Conclusions
Compared with BP group, denosumab group displayed significantly increased H-BMD at 6 months, while L-BMD and H-BMD were significantly increased for 24 months in both groups. Thus, regardless of BP pre-treatment, denosumab could be a good agent in OP with RA.
Similar content being viewed by others
References
Kvien TK, Haugeberg G, Uhlig T, Falch JA, Halse JI, Lems WF, Dijkmans BA, Woolf AD (2000) Data driven attempt to create a clinical algorithm for identification of women with rheumatoid arthritis at high risk of osteoporosis. Ann Rheum Dis 59:805–811
Gauri LA, Fatima Q, Diggi S, Khan A, Liyakat A, Ajay BR (2017) Study of bone mineral density (BMD) in patients with rheumatoid arthritis and its co-relation with severity of the disease. J Assoc Physicians India 65:26–30
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
Black DM, Bauer DC, Schwartz AV, Cummings SR, Rosen CJ (2012) Continuing bisphosphonate treatment for osteoporosis—for whom and for how long? N Engl J Med 366(22):2051–2053
McClung MR, Lewiecki EM, Cohen SB, Bolognese MA, Woodson GC, Moffett AH, Peacock M, Miller PD, Lederman SN, Chesnut CH, Lain D, Kivitz AJ, Holloway DL, Zhang C, Peterson MC, Bekker PJ, AMG 162 Bone Loss Study Group (2006) Denosumab in postmenopausal women with low bone mineral density. N Engl J Med 354:821–831
Silva I, Branco JC (2012) Denosumab: recent update in postmenopausal osteoporosis. Acta Reumatol Port 37:302–313 Review
Nakamura Y, Suzuki T, Yoshida T, Yamazaki H, Kato H (2017) Vitamin D and calcium are required during denosumab treatment in osteoporosis with rheumatoid Arthritis. Nutrients 9(5):E428 https://doi.org/10.3390/nu9050428
Kamimura M, Nakamura Y, Ikegami S, Uchiyama S, Kato H, Taguchi A (2017) Significant improvement of bone mineral density and bone turnover markers by denosumab therapy in bisphosphonate-unresponsive patients. Osteoporos Int 28:1757–1758
Kinoshita H, Miyakoshi N, Kashiwagura T, Kasukawa Y, Sugimura Y, Shimada Y (2017) Comparison of the efficacy of denosumab and bisphosphonates for treating secondary osteoporosis in patients with rheumatoid arthritis. Mod Rheumatol 27(4):582-586
Soen S (2014) New diagnostic criteria and guidelines on osteoporosis. Diagnostic criteria for primary osteoporosis : year 2012 revision. (article in Japanese). Clin Calcium 24:323–329
van der Linden MP, Knevel R, Huizinga TW, van der Helm-van Mil AH (2011) Classification of rheumatoid arthritis: comparison of the 1987 American College of Rheumatology criteria and the 2010 American College of Rheumatology/European League Against Rheumatism criteria. Arthritis Rheum 63:37–42
Nakamura Y, Suzuki T, Kamimura M, Ikegami S, Uchiyama S, Kato H (2017) Alfacalcidol increases the therapeutic efficacy of Ibandronate on bone mineral density in Japanese women with primary osteoporosis. Tohoku J Exp Med 241:319–326
Boyle WJ, Simonet WS, Lacey DL (2003) Osteoclast differentiation and activation. Nature 423(6937):337–342
Mochizuki T, Yano K, Ikari K, Kawakami K, Hiroshima R, Koenuma N, Ishibashi M, Momohara S (2017) Effects of denosumab treatment on bone mineral density and joint destruction in patients with rheumatoid arthritis. J Bone Miner Metab https://doi.org/10.1007/s00774-017-0848-1
Kim D, Cho SK, Choi CB, Jun JB, Kim TH, Lee HS, Lee J, Lee SS, Yoo DH, Yoo WH, Sung YK, Bae SC (2016) Incidence and risk factors of fractures in patients with rheumatoid arthritis: an Asian prospective cohort study. Rheumatol Int 36:1205–1214
Ishiguro S, Ito K, Nakagawa S, Hataji O, Sudo A (2017) The clinical benefits of denosumab for prophylaxis of steroid-induced osteoporosis in patients with pulmonary disease. Arch Osteoporos 12:44
Sawamura M, Komatsuda A, Togashi M, Wakui H, Takahashi N (2017) Effects of denosumab on bone metabolic markers and bone mineral density in patients treated with glucocorticoids. Intern Med 56:631–636
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
This investigation was approved by the Institutional Ethical Review Board of Shinshu University School of Medicine no. 2365), Japan, prior to its commencement.
Conflict of interest
None.
Rights and permissions
About this article
Cite this article
Nakamura, Y., Suzuki, T. & Kato, H. Denosumab significantly improves bone mineral density with or without bisphosphonate pre-treatment in osteoporosis with rheumatoid arthritis. Arch Osteoporos 12, 80 (2017). https://doi.org/10.1007/s11657-017-0371-y
Received:
Accepted:
Published:
DOI: https://doi.org/10.1007/s11657-017-0371-y