Osteoporosis International

, Volume 27, Issue 1, pp 351–359 | Cite as

Effects of switching weekly alendronate or risedronate to monthly minodronate in patients with rheumatoid arthritis: a 12-month prospective study

  • K. Ebina
  • T. Noguchi
  • M. Hirao
  • J. Hashimoto
  • S. Kaneshiro
  • M. Yukioka
  • H. Yoshikawa
Original Article



Switching weekly ALN or RIS to monthly MIN in patients with RA, of whom two-thirds were treated with low-dose PSL, significantly decreased bone turnover markers and increased BMD at 12 months, suggesting that monthly MIN may be an effective alternative treatment option of oral bisphosphonate treatment.


The aim of this prospective, observational study was to evaluate the effects of switching weekly alendronate (ALN 35 mg) or risedronate (RIS 17.5 mg) to monthly minodronate (MIN 50 mg) in patients with rheumatoid arthritis (RA).


Patient characteristics were as follows: n = 172; 155 postmenopausal women, age 65.5 (44–87) years; T-score of lumbar spine (LS), −1.4; total hip (TH), −1.8; femoral neck (FN), −2.1; dose and rate of oral prednisolone (2.3 mg/day), 69.1 %; prior duration of ALN or RIS, 46.6 months; were allocated, based on their preference, to either the (1) continue group (n = 88), (2) switch-from-ALN group (n = 44), or (3) switch-from-RIS group (n = 40).


After 12 months, increase in BMD was significantly greater in group 3 compared to group 1: LS (4.1 vs 1.2 %; P < 0.001), TH (1.9 vs −0.7 %; P < 0.01), and FN (2.7 vs −0.5 %; P < 0.05); and in group 2 compared to group 1: LS (3.2 vs 1.2 %; P < 0.05) and TH (1.5 vs −0.7 %; P < 0.01). The decrease in bone turnover markers was significantly greater in group 3 compared to group 1: TRACP-5b (−37.3 vs 2.5 %; P < 0.001), PINP (−24.7 vs −6.2 %; P < 0.05), and ucOC (−39.2 vs 13.0 %; P < 0.05); and in group 2 compared to group 1: TRACP-5b (−12.5 vs 2.5 %; P < 0.05) at 12 months.


Switching weekly ALN or RIS to monthly MIN in patients with RA may be an effective alternative treatment option of oral bisphosphonate treatment.


Alendronate Minodronate Osteoporosis Rheumatoid arthritis Risedronate 



The authors thank Dr. Kenrin Shi for his excellent cooperation in conducting the study.

Compliance with ethical standards

This observational study was conducted in accordance with the ethical standards of the Declaration of Helsinki and was approved by ethical review boards at the clinical center (approval number 11273-2; Osaka University, Graduate School of Medicine). Written informed consent was obtained from individual patients included in the study.

Conflicts of interest

This research was funded by Astellas Pharma, Inc. The funder had no role in the study design, data collection, data analysis, decision to publish, or preparation of the manuscript. Kosuke Ebina, Takaaki Noguchi, Makoto Hirao, Jun Hashimoto, Shoichi Kaneshiro, Masao Yukioka, and Hideki Yoshikawa declare that they have no conflict of interest.


  1. 1.
    Peel NF, Moore DJ, Barrington NA, Bax DE, Eastell R (1995) Risk of vertebral fracture and relationship to bone mineral density in steroid treated rheumatoid arthritis. Ann Rheum Dis 54:801–806PubMedPubMedCentralCrossRefGoogle Scholar
  2. 2.
    van Staa TP, Geusens P, Bijlsma JW, Leufkens HG, Cooper C (2006) Clinical assessment of the long-term risk of fracture in patients with rheumatoid arthritis. Arthritis Rheum 54:3104–3112PubMedCrossRefGoogle Scholar
  3. 3.
    Wright NC, Lisse JR, Walitt BT, Eaton CB, Chen Z (2011) Arthritis increases the risk for fractures—results from the women’s health initiative. J Rheumatol 38:1680–1688PubMedPubMedCentralCrossRefGoogle Scholar
  4. 4.
    Braun T, Schett G (2012) Pathways for bone loss in inflammatory disease. Curr Osteoporos Rep 10:101–108PubMedCrossRefGoogle Scholar
  5. 5.
    Ebina K, Oshima K, Matsuda M et al (2009) Adenovirus-mediated gene transfer of adiponectin reduces the severity of collagen-induced arthritis in mice. Biochem Biophys Res Commun 378:186–191PubMedCrossRefGoogle Scholar
  6. 6.
    Kaneshiro S, Ebina K, Shi K, Higuchi C, Hirao M, Okamoto M, Koizumi K, Morimoto T, Yoshikawa H, Hashimoto J (2014) IL-6 negatively regulates osteoblast differentiation through the SHP2/MEK2 and SHP2/Akt2 pathways in vitro. J Bone Miner Metab 32:378–392PubMedCrossRefGoogle Scholar
  7. 7.
    Noguchi T, Ebina K, Hirao M et al (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 465:638–643PubMedCrossRefGoogle Scholar
  8. 8.
    Cortet B, Guyot MH, Solau E, Pigny P, Dumoulin F, Flipo RM, Marchandise X, Delcambre B (2000) Factors influencing bone loss in rheumatoid arthritis: a longitudinal study. Clin Exp Rheumatol 18:683–690PubMedGoogle Scholar
  9. 9.
    Kanis JA, Johansson H, Oden A et al (2004) A meta-analysis of prior corticosteroid use and fracture risk. J Bone Miner Res 19:893–899PubMedCrossRefGoogle Scholar
  10. 10.
    Van Staa TP, Leufkens HG, Abenhaim L, Zhang B, Cooper C (2000) Use of oral corticosteroids and risk of fractures. J Bone Miner Res 15:993–1000PubMedCrossRefGoogle Scholar
  11. 11.
    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
  12. 12.
    Sakai A, Ikeda S, Okimoto N et al (2014) Clinical efficacy and treatment persistence of monthly minodronate for osteoporotic patients unsatisfied with, and shifted from, daily or weekly bisphosphonates: the BP-MUSASHI study. Osteoporos Int 25:2245–2253PubMedPubMedCentralCrossRefGoogle Scholar
  13. 13.
    Orimo H, Nakamura T, Hosoi T et al (2012) Japanese 2011 guidelines for prevention and treatment of osteoporosis—executive summary. Arch Osteoporos 7:3–20PubMedPubMedCentralCrossRefGoogle Scholar
  14. 14.
    Nawata H, Soen S, Takayanagi R et al (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 23:105–109PubMedCrossRefGoogle Scholar
  15. 15.
    Arnett FC, Edworthy SM, Bloch DA et al (1988) The American rheumatism association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 31:315–324PubMedCrossRefGoogle Scholar
  16. 16.
    Ebina K, Shi K, Hirao M, Kaneshiro S, Morimoto T, Koizumi K, Yoshikawa H, Hashimoto J (2013) Vitamin K2 administration is associated with decreased disease activity in patients with rheumatoid arthritis. Mod Rheumatol 23:1001–1007PubMedCrossRefGoogle Scholar
  17. 17.
    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 66:1221–1226PubMedPubMedCentralCrossRefGoogle Scholar
  18. 18.
    Ebina K, Noguchi T, Hirao M, Kaneshiro S, Tsukamoto Y, Yoshikawa H (2015) Comparison of the effects of 12 months of monthly minodronate monotherapy and monthly minodronate combination therapy with vitamin K or eldecalcitol in patients with primary osteoporosis. J Bone Miner MetabGoogle Scholar
  19. 19.
    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 25:2755–2765PubMedCrossRefGoogle Scholar
  20. 20.
    Booth SL, Centi A, Smith SR, Gundberg C (2013) The role of osteocalcin in human glucose metabolism: marker or mediator? Nat Rev Endocrinol 9:43–55PubMedPubMedCentralCrossRefGoogle Scholar
  21. 21.
    Ebina K, Hashimoto J, Shi K, Kashii M, Hirao M, Yoshikawa H (2014) Undercarboxylated osteocalcin may be an attractive marker of teriparatide treatment in RA patients: response to Mokuda. Osteoporos IntGoogle Scholar
  22. 22.
    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 19:733–759PubMedCrossRefGoogle Scholar
  23. 23.
    Reid DM, Hosking D, Kendler D et al (2008) A comparison of the effect of alendronate and risedronate on bone mineral density in postmenopausal women with osteoporosis: 24-month results from FACTS-International. Int J Clin Pract 62:575–584PubMedCrossRefGoogle Scholar
  24. 24.
    Silverman SL, Watts NB, Delmas PD, Lange JL, Lindsay R (2007) Effectiveness of bisphosphonates on nonvertebral and hip fractures in the first year of therapy: the risedronate and alendronate (REAL) cohort study. Osteoporos Int 18:25–34PubMedPubMedCentralCrossRefGoogle Scholar
  25. 25.
    Ebetino FH, Hogan AM, Sun S et al (2011) The relationship between the chemistry and biological activity of the bisphosphonates. Bone 49:20–33PubMedCrossRefGoogle Scholar
  26. 26.
    Tsubaki M, Komai M, Itoh T et al (2014) Nitrogen-containing bisphosphonates inhibit RANKL- and M-CSF-induced osteoclast formation through the inhibition of ERK1/2 and Akt activation. J Biomed Sci 21:10PubMedPubMedCentralCrossRefGoogle Scholar
  27. 27.
    Yamagami Y, Mashiba T, Iwata K, Tanaka M, Nozaki K, Yamamoto T (2013) Effects of minodronic acid and alendronate on bone remodeling, microdamage accumulation, degree of mineralization and bone mechanical properties in ovariectomized cynomolgus monkeys. Bone 54:1–7PubMedCrossRefGoogle Scholar
  28. 28.
    Plotkin LI, Manolagas SC, Bellido T (2006) Dissociation of the pro-apoptotic effects of bisphosphonates on osteoclasts from their anti-apoptotic effects on osteoblasts/osteocytes with novel analogs. Bone 39:443–452PubMedCrossRefGoogle Scholar
  29. 29.
    Follet H, Li J, Phipps RJ, Hui S, Condon K, Burr DB (2007) Risedronate and alendronate suppress osteocyte apoptosis following cyclic fatigue loading. Bone 40:1172–1177PubMedCrossRefGoogle Scholar
  30. 30.
    Feng Z, Zeng S, Wang Y, Zheng Z, Chen Z (2013) Bisphosphonates for the prevention and treatment of osteoporosis in patients with rheumatic diseases: a systematic review and meta-analysis. PLoS One 8:e80890PubMedPubMedCentralCrossRefGoogle Scholar
  31. 31.
    Adachi JD, Saag KG, Delmas PD et al (2001) Two-year effects of alendronate on bone mineral density and vertebral fracture in patients receiving glucocorticoids: a randomized, double-blind, placebo-controlled extension trial. Arthritis Rheum 44:202–211PubMedCrossRefGoogle Scholar
  32. 32.
    Wallach S, Cohen S, Reid DM et al (2000) Effects of risedronate treatment on bone density and vertebral fracture in patients on corticosteroid therapy. Calcif Tissue Int 67:277–285PubMedCrossRefGoogle Scholar

Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2015

Authors and Affiliations

  • K. Ebina
    • 1
  • T. Noguchi
    • 1
  • M. Hirao
    • 1
  • J. Hashimoto
    • 2
  • S. Kaneshiro
    • 3
  • M. Yukioka
    • 4
  • H. Yoshikawa
    • 1
  1. 1.Department of Orthopaedic Surgery, Graduate School of MedicineOsaka UniversitySuitaJapan
  2. 2.Department of Rheumatology, National Hospital OrganizationOsaka Minami MedicalCenterKawachinaganoJapan
  3. 3.Department of Orthopaedic Surgery, Japan Community Health Care OrganizationOsaka HospitalFukushima wardJapan
  4. 4.Department of RheumatologyYukioka HospitalKita-kuJapan

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