Assessment of the effects of switching oral bisphosphonates to denosumab or daily teriparatide in patients with rheumatoid arthritis
The aim of this observational, non-randomized study was to clarify the unknown effects of switching oral bisphosphonates (BPs) to denosumab (DMAb) or daily teriparatide (TPTD) in patients with rheumatoid arthritis (RA). The characteristics of the 194 female patients included in the study were 183 postmenopausal, age 65.9 years, lumbar spine (LS) T score −1.8, femoral neck (FN) T score −2.3, dose and rate of taking oral prednisolone (3.6 mg/day) 75.8%, and prior BP treatment duration 40.0 months. The patients were allocated to (1) the BP-continue group (n = 80), (2) the switch-to-DMAb group (n = 74), or (3) the switch-to-TPTD group (n = 40). After 18 months, the increase in bone mineral density (BMD) was significantly greater in the switch-to-DMAb group than in the BP-continue group (LS 5.2 vs 2.3%, P < 0.01; FN 3.8 vs 0.0%, P < 0.01) and in the switch-to-TPTD group than in the BP-continue group (LS 9.0 vs 2.3%, P < 0.001; FN 4.9 vs 0.0%, P < 0.01). Moreover, the switch-to-TPTD group showed a higher LS BMD (P < 0.05) and trabecular bone score (TBS) (2.1 vs −0.7%; P < 0.05) increase than the switch-to-DMAb group. Clinical fracture incidence during this period was 8.8% in the BP-continue group, 4.1% in the switch-to-DMAb group, and 2.5% in the switch-to-TPTD group. Both the switch-to-DMAb group and the switch-to-TPTD group showed significant increases in LS and FN BMD, and the switch-to-TPTD group showed a higher increase in TBS compared to the BP-continue group at 18 months. Switching BPs to DMAb or TPTD in female RA may provide some useful osteoporosis treatment options.
KeywordsBisphosphonate Denosumab Osteoporosis Rheumatoid arthritis Teriparatide
The authors would like to thank Dr. Masao Yukioka and Dr. Kenrin Shi for their excellent cooperation in conducting the study.
Compliance with ethical standards
Conflict of interest
K. Ebina, M. Hirao, J. Hashimoto, and H. Yoshikawa have received research grants from Astellas Pharma and Eisai Co. Ltd. K. Ebina, M. Hirao, K. Hagihara, and H. Yoshikawa have received research grants from Daiichi Sankyo. H. Yoshikawa has received a research grant from MSD. K. Hagihara has received a research grant from Eli Lily. K. Ebina has received payments for lectures from Daiichi Sankyo. M. Kashii, K. Kitaguchi, H. Matsuoka, T. Iwahashi, R. Chijimatsu declare that they have no conflicts of interest. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.
- 8.Noguchi T, Ebina K, Hirao M, Kawase R, Ohama T, Yamashita S, Morimoto T, Koizumi K, Kitaguchi K, Matsuoka H, Kaneshiro S, Yoshikawa H (2015) Progranulin plays crucial roles in preserving bone mass by inhibiting TNF-alpha-induced osteoclastogenesis and promoting osteoblastic differentiation in mice. Biochem Biophys Res Commun 465:638–643CrossRefPubMedGoogle Scholar
- 14.Saag KG, Zanchetta JR, Devogelaer JP, Adler RA, Eastell R, See K, Krege JH, Krohn K, Warner MR (2009) Effects of teriparatide versus alendronate for treating glucocorticoid-induced osteoporosis: thirty-six-month results of a randomized, double-blind, controlled trial. Arthritis Rheum 60:3346–3355CrossRefPubMedGoogle Scholar
- 19.Takeuchi T, Tanaka Y, Ishiguro N, Yamanaka H, Yoneda T, Ohira T, Okubo N, Genant HK, van der Heijde D (2016) Effect of denosumab on Japanese patients with rheumatoid arthritis: a dose-response study of AMG 162 (Denosumab) in patients with Rheumatoid arthritis on methotrexate to Validate inhibitory effect on bone Erosion (DRIVE)—a 12-month, multicentre, randomised, double-blind, placebo-controlled, phase II clinical trial. Ann Rheum Dis 75:983–990CrossRefPubMedGoogle Scholar
- 21.Orimo H, Nakamura T, Hosoi T, Iki M, Uenishi K, Endo N, Ohta H, Shiraki M, Sugimoto T, Suzuki T, Soen S, Nishizawa Y, Hagino H, Fukunaga M, Fujiwara S (2012) Japanese 2011 guidelines for prevention and treatment of osteoporosis—executive summary. Arch Osteoporos 7:3–20CrossRefPubMedPubMedCentralGoogle Scholar
- 22.Nawata H, Soen S, Takayanagi R, Tanaka I, Takaoka K, Fukunaga M, Matsumoto T, Suzuki Y, Tanaka H, Fujiwara S, Miki T, Sagawa A, Nishizawa Y, Seino Y (2005) Guidelines on the management and treatment of glucocorticoid-induced osteoporosis of the Japanese Society for Bone and Mineral Research (2004). J Bone Miner Metab 23:105–109CrossRefPubMedGoogle Scholar
- 25.Matsui T, Kuga Y, Kaneko A, Nishino J, Eto Y, Chiba N, Yasuda M, Saisho K, Shimada K, Tohma S (2007) Disease activity score 28 (DAS28) using C-reactive protein underestimates disease activity and overestimates EULAR response criteria compared with DAS28 using erythrocyte sedimentation rate in a large observational cohort of rheumatoid arthritis patients in Japan. Ann Rheum Dis 66:1221–1226CrossRefPubMedPubMedCentralGoogle Scholar
- 27.Hans D, Barthe N, Boutroy S, Pothuaud L, Winzenrieth R, Krieg MA (2011) Correlations between trabecular bone score, measured using anteroposterior dual-energy X-ray absorptiometry acquisition, and 3-dimensional parameters of bone microarchitecture: an experimental study on human cadaver vertebrae. J Clin Densitom 14:302–312CrossRefPubMedGoogle Scholar
- 30.Aloia J, Bojadzievski T, Yusupov E, Shahzad G, Pollack S, Mikhail M, Yeh J (2010) The relative influence of calcium intake and vitamin D status on serum parathyroid hormone and bone turnover biomarkers in a double-blind, placebo-controlled parallel group, longitudinal factorial design. J Clin Endocrinol Metab 95:3216–3224CrossRefPubMedGoogle Scholar
- 31.Chaitou A, Boutroy S, Vilayphiou N, Varennes A, Richard M, Blaizot S, Munoz F, Delmas PD, Goudable J, Chapurlat R, Szulc P (2011) Association of bone microarchitecture with parathyroid hormone concentration and calcium intake in men: the STRAMBO study. Eur J Endocrinol 165:151–159CrossRefPubMedGoogle Scholar
- 35.Kostenuik PJ, Smith SY, Samadfam R, Jolette J, Zhou L, Ominsky MS (2015) Effects of denosumab, alendronate, or denosumab following alendronate on bone turnover, calcium homeostasis, bone mass and bone strength in ovariectomized cynomolgus monkeys. J Bone Miner Res 30:657–669CrossRefPubMedGoogle Scholar
- 39.Obermayer-Pietsch BM, Marin F, McCloskey EV, Hadji P, Farrerons J, Boonen S, Audran M, Barker C, Anastasilakis AD, Fraser WD, Nickelsen T (2008) Effects of two years of daily teriparatide treatment on BMD in postmenopausal women with severe osteoporosis with and without prior antiresorptive treatment. J Bone Miner Res 23:1591–1600CrossRefPubMedGoogle Scholar
- 44.Joo NS, Dawson-Hughes B, Kim YS, Oh K, Yeum KJ (2013) Impact of calcium and vitamin D insufficiencies on serum parathyroid hormone and bone mineral density: analysis of the fourth and fifth Korea National Health and Nutrition Examination Survey (KNHANES IV-3, 2009 and KNHANES V-1, 2010). J Bone Miner Res 28:764–770CrossRefPubMedGoogle Scholar