Osteoporosis International

, Volume 29, Issue 7, pp 1627–1636 | Cite as

Impact of switching oral bisphosphonates to denosumab or daily teriparatide on the progression of radiographic joint destruction in patients with biologic-naïve rheumatoid arthritis

  • K. Ebina
  • M. Hirao
  • J. Hashimoto
  • H. Matsuoka
  • T. Iwahashi
  • R. Chijimatsu
  • Y. Etani
  • G. Okamura
  • A. Miyama
  • H. Yoshikawa
Original Article



In biologic-naïve female RA patients, switching oral BPs to DMAb significantly reduced radiographic joint destruction compared to continuing oral BPs or switching to TPTD at 12 months, which were significantly associated with a decrease of a bone resorption marker at 6 months.


The aim of this study was to clarify the effects of switching oral bisphosphonates (BPs) to denosumab (DMAb) or daily teriparatide (TPTD) on the progression of radiographic joint destruction in patients with biologic-naïve rheumatoid arthritis (RA).


A retrospective, case-controlled study involving 90 female RA patients (mean age 68.2 years, 96.7% postmenopausal, disease activity score assessing 28 joints with CRP (DAS28-CRP) 2.4, methotrexate treatment 81.1%, prednisolone treatment 68.9%, and prior BP treatment 44.8 months), who were allocated depending on each patient’s and physician’s wishes, to (1) the BP-continue group (n = 30), (2) the switch-to-DMAb group (n = 30), or (3) the switch-to-TPTD group (n = 30), was conducted. Patients were retrospectively selected to minimize the difference of possible clinical backgrounds that may affect the joint destruction of RA. The primary endpoint was to clarify the change of the modified total Sharp score (mTSS) from baseline to 12 months.


After 12 months, the mean changes of the modified Sharp erosion score were significantly lower in the switch-to-DMAb group (0.2 ± 0.1; mean ± standard error) than in the switch-to-TPTD group (1.3 ± 0.5; P < 0.05), and mTSS was significantly lower in the switch-to-DMAb group (0.3 ± 0.2) than in the BP-continue group (1.0 ± 0.3; P < 0.05) and the switch-to-TPTD group (1.7 ± 0.6; P < 0.05). The logistic regression analysis showed that mTSS changes were significantly associated with the percent changes of TRACP-5b at 6 months (β = 0.30, 95% CI = 0.002–0.016; P < 0.01).


Changes of systemic bone turnover induced by switching BPs to DMAb or TPTD may affect not only systemic bone mass, but also local joint destruction, and its clinical relevance should be considered comprehensively.


Bisphosphonate Denosumab Joint destruction 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

Conflicts 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, and H Yoshikawa have received research grants from Daiichi Sankyo. H Yoshikawa has received research grants from MSD. K Ebina has received payments for lectures from Astellas Pharma, Chugai Pharmaceutical, Eisai Co. Ltd., Ono Pharmaceutical, Daiichi Sankyo, and Eli Lily. H Matsuoka, T Iwahashi, R Chijimatsu, Y Etani, G Okamura, and A Miyama declare that they have no conflicts of interest.


  1. 1.
    Schett G, Hayer S, Zwerina J, Redlich K, Smolen JS (2005) Mechanisms of disease: the link between RANKL and arthritic bone disease. Nat Clin Pract Rheumatol 1:47–54CrossRefPubMedGoogle Scholar
  2. 2.
    Scott DL, Wolfe F, Huizinga TW (2010) Rheumatoid arthritis. Lancet 376:1094–1108CrossRefPubMedGoogle Scholar
  3. 3.
    Braun T, Schett G (2012) Pathways for bone loss in inflammatory disease. Curr Osteoporos Rep 10:101–108CrossRefPubMedGoogle Scholar
  4. 4.
    Jansen LM, van der Horst-Bruinsma I, Lems WF, van Schaardenburg D, van de Stadt R, de Koning M, Dijkmans BA (2004) Serological bone markers and joint damage in early polyarthritis. J Rheumatol 31:1491–1496PubMedGoogle Scholar
  5. 5.
    Syversen SW, Goll GL, van der Heijde D, Landewe R, Gaarder PI, Odegard S, Haavardsholm EA, Kvien TK (2009) Cartilage and bone biomarkers in rheumatoid arthritis: prediction of 10-year radiographic progression. J Rheumatol 36:266–272CrossRefPubMedGoogle Scholar
  6. 6.
    Rossini M, Adami G, Viapiana O, Idolazzi L, Orsolini G, Fassio A, Giollo A, Gatti D (2017) Osteoporosis: an independent determinant of bone erosions in rheumatoid arthritis? J Bone Miner Res 32:2142–2143CrossRefPubMedGoogle Scholar
  7. 7.
    Russell RG, Watts NB, Ebetino FH, Rogers MJ (2008) Mechanisms of action of bisphosphonates: similarities and differences and their potential influence on clinical efficacy. Osteoporos Int 19:733–759CrossRefPubMedGoogle Scholar
  8. 8.
    Kendler DL, Roux C, Benhamou CL, Brown JP, Lillestol M, Siddhanti S, Man HS, San Martin J, Bone HG (2010) Effects of denosumab on bone mineral density and bone turnover in postmenopausal women transitioning from alendronate therapy. J Bone Miner Res 25:72–81CrossRefPubMedGoogle Scholar
  9. 9.
    Finkelstein JS, Wyland JJ, Lee H, Neer RM (2010) Effects of teriparatide, alendronate, or both in women with postmenopausal osteoporosis. J Clin Endocrinol Metab 95:1838–1845CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Ebina K, Hirao M, Hashimoto J, Hagihara K, Kashii M, Kitaguchi K, Matsuoka H, Iwahashi T, Chijimatsu R, Yoshikawa H (2017) Assessment of the effects of switching oral bisphosphonates to denosumab or daily teriparatide in patients with rheumatoid arthritis. J Bone Miner MetabGoogle Scholar
  11. 11.
    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
  12. 12.
    Ebina K, Hashimoto J, Shi K, Kashii M, Hirao M, Yoshikawa H (2014) Comparison of the effect of 18-month daily teriparatide administration on patients with rheumatoid arthritis and postmenopausal osteoporosis patients. Osteoporos Int 25:2755–2765CrossRefPubMedGoogle Scholar
  13. 13.
    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
  14. 14.
    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, The Subcommittee to Study Diagnostic Criteria for Glucocorticoid-Induced Osteoporosis (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
  15. 15.
    Arnett FC, Edworthy SM, Bloch DA, Mcshane DJ, Fries JF, Cooper NS, Healey LA, Kaplan SR, Liang MH, Luthra HS, Medsger TA, Mitchell DM, Neustadt DH, Pinals RS, Schaller JG, Sharp JT, Wilder RL, Hunder GG (1988) The American rheumatism association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 31:315–324CrossRefPubMedGoogle Scholar
  16. 16.
    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
  17. 17.
    Chieffo A, Meliga E, Latib A, Park SJ, Onuma Y, Capranzano P, Valgimigli M, Jegere S, Makkar RR, Palacios IF, Kim YH, Buszman PE, Chakravarty T, Sheiban I, Mehran R, Naber C, Margey R, Agnihotri A, Marra S, Capodanno D, Leon MB, Moses JW, Fajadet J, Lefevre T, Morice MC, Erglis A, Tamburino C, Alfieri O, Serruys PW, Colombo A (2012) Drug-eluting stent for left main coronary artery disease. The DELTA registry: a multicenter registry evaluating percutaneous coronary intervention versus coronary artery bypass grafting for left main treatment. JACC Cardiovasc Interv 5:718–727CrossRefPubMedGoogle Scholar
  18. 18.
    Hasegawa T, Kaneko Y, Izumi K, Takeuchi T (2017) Efficacy of denosumab combined with bDMARDs on radiographic progression in rheumatoid arthritis. Joint Bone Spine 84:379–380CrossRefPubMedGoogle Scholar
  19. 19.
    Bruynesteyn K, Van Der Heijde D, Boers M et al (2002) Detecting radiological changes in rheumatoid arthritis that are considered important by clinical experts: influence of reading with or without known sequence. J Rheumatol 29:2306–2312PubMedGoogle Scholar
  20. 20.
    Ebina K, Hashimoto J, Shi K, Kashii M, Hirao M, Yoshikawa H (2015) Undercarboxylated osteocalcin may be an attractive marker of teriparatide treatment in RA patients: response to Mokuda. Osteoporos Int 26:1445CrossRefPubMedGoogle Scholar
  21. 21.
    Boutroy S, Hans D, Sornay-Rendu E, Vilayphiou N, Winzenrieth R, Chapurlat R (2013) Trabecular bone score improves fracture risk prediction in non-osteoporotic women: the OFELY study. Osteoporos Int 24:77–85CrossRefPubMedGoogle Scholar
  22. 22.
    Nenonen A, Cheng S, Ivaska KK, Alatalo SL, Lehtimäki T, Schmidt-Gayk H, Uusi-Rasi K, Heinonen A, Kannus P, Sievänen H, Vuori I, Väänänen HK, Halleen JM (2005) Serum TRACP 5b is a useful marker for monitoring alendronate treatment: comparison with other markers of bone turnover. J Bone Miner Res 20:1804–1812CrossRefPubMedGoogle Scholar
  23. 23.
    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
  24. 24.
    Syversen SW, Gaarder PI, Goll GL, Odegard S, Haavardsholm EA, Mowinckel P, van der Heijde D, Landewe R, Kvien TK (2008) High anti-cyclic citrullinated peptide levels and an algorithm of four variables predict radiographic progression in patients with rheumatoid arthritis: results from a 10-year longitudinal study. Ann Rheum Dis 67:212–217CrossRefPubMedGoogle Scholar
  25. 25.
    Rossini M, Bagnato G, Frediani B, Iagnocco A, LAM G, Minisola G, Caminiti M, Varenna M, Adami S (2011) Relationship of focal erosions, bone mineral density, and parathyroid hormone in rheumatoid arthritis. J Rheumatol 38:997–1002CrossRefPubMedGoogle Scholar
  26. 26.
    Dunford JE, Thompson K, Coxon FP, Luckman SP, Hahn FM, Poulter CD, Ebetino FH, Rogers MJ (2001) Structure-activity relationships for inhibition of farnesyl diphosphate synthase in vitro and inhibition of bone resorption in vivo by nitrogen-containing bisphosphonates. J Pharmacol Exp Ther 296:235–242PubMedGoogle Scholar
  27. 27.
    Le Goff B, Soltner E, Charrier C, Maugars Y, Redini F, Heymann D, Berthelot JM (2009) A combination of methotrexate and zoledronic acid prevents bone erosions and systemic bone mass loss in collagen induced arthritis. Arthritis Res Ther 11:R185CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    McQueen F, Lloyd R, Doyle A, Robinson E, Lobo M, Exeter M, Taylor WJ, Jones P, Reid IR, Dalbeth N (2011) Zoledronic acid does not reduce MRI erosive progression in PsA but may suppress bone oedema: the Zoledronic acid in psoriatic arthritis (ZAPA) study. Ann Rheum Dis 70:1091–1094CrossRefPubMedGoogle Scholar
  29. 29.
    Dalbeth N, Aati O, Gamble GD, Horne A, House ME, Roger M, Doyle AJ, Chhana A, McQueen FM, Reid IR (2014) Zoledronate for prevention of bone erosion in tophaceous gout: a randomised, double-blind, placebo-controlled trial. Ann Rheum Dis 73:1044–1051CrossRefPubMedGoogle Scholar
  30. 30.
    Solomon DH, Kay J, Duryea J, Lu B, Bolster MB, Yood RA, Han R, Ball S, Coleman C, Lo E, Wohlfahrt A, Sury M, Yin M, Yu Z, Zak A, Gravallese EM (2017) Effects of teriparatide on joint erosions in rheumatoid arthritis: a randomized controlled trial. Arthritis Rheumatol 69:1741–1750CrossRefPubMedGoogle Scholar
  31. 31.
    Rossini M, Adami G, Viapiana O, Idolazzi L, Gatti D (2016) Denosumab, cortical bone and bone erosions in rheumatoid arthritis. Ann Rheum Dis 75:e70CrossRefPubMedGoogle Scholar
  32. 32.
    Zebaze RM, Libanati C, Austin M, Ghasem-Zadeh A, Hanley DA, Zanchetta JR, Thomas T, Boutroy S, Bogado CE, Bilezikian JP, Seeman E (2014) Differing effects of denosumab and alendronate on cortical and trabecular bone. Bone 59:173–179CrossRefPubMedGoogle Scholar
  33. 33.
    Adami G, Rossini M, Viapiana O, Fassio A, Idolazzi L, Orsolini G, Gatti D (2017) No effects of teriparatide on joint erosions in rheumatoid arthritis: an expected result. Arthritis RheumatolGoogle Scholar
  34. 34.
    Keaveny TM, McClung MR, Wan X, Kopperdahl DL, Mitlak BH, Krohn K (2012) Femoral strength in osteoporotic women treated with teriparatide or alendronate. Bone 50:165–170CrossRefPubMedGoogle Scholar

Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2018

Authors and Affiliations

  1. 1.Department of Orthopaedic SurgeryOsaka University, Graduate School of MedicineOsakaJapan
  2. 2.Department of RheumatologyNational Hospital Organization, Osaka Minami Medical CenterOsakaJapan

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