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Clinical efficacy of oral risedronate therapy in Japanese patients with Paget’s disease of bone

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Abstract

Paget’s disease of bone (PDB) is a chronic disorder characterized by localized bone regions with excessive bone turnover. Although oral risedronate (17.5 mg daily for 8 weeks) was recently approved in Japan, its efficacy is not well understood. We retrospectively examined the efficacy of oral risedronate in PDB patients in a clinical setting. Eleven patients whose serum alkaline phosphatase (ALP) level exceeded the upper limit of the normal range were treated. Patients whose ALP levels normalized and remained so for 12 months after therapy initiation were defined as responders. Treatment was repeated if bone pain recurred or if serum ALP levels increased at least 25% above the nadir. Six patients (55%) were responsive to the therapy. A higher prevalence of skull lesions, higher serum calcium levels at treatment initiation and antecedent treatments of bisphosphonates were predictors of resistance against the therapy. Fresh frozen serum samples obtained from some treatment sessions were evaluated for metabolic bone markers such as bone-specific ALP (BAP), type I procollagen N-terminal pro-peptide (PINP), N-treminal crosslinking telopeptide of type I collagen and C-treminal crosslinking telopeptide of type I collagen (CTX). A significant reduction of P1NP preceded that of serum ALP levels in the responders, which was followed by a similar occurrence for BAP and osteocalcin (BGP) levels. A temporary decrease in CTX levels was noted. No significant changes in markers (including ALP level) were observed in non-responder and repeat-treatment groups. P1NP levels may be more useful than ALP levels in assessing treatment efficacy. Repeat treatment effectiveness for the repeat-treatment group was limited.

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References

  1. Hashimoto J, Ohno I, Nakatsuka K, Yoshimura N, Takata S, Zamma M, Yabe H, Abe S, Terada M, Yoh K, Fukunaga M, Cooper C, Morii H, Yoshikawa H, Japanese Committee on Clinical Guidelines of D, Treatment of Paget’s Disease of Bone of the Japan Osteoporosis S (2006) Prevalence and clinical features of Paget’s disease of bone in Japan. J Bone Miner Metab 24:186–190

    Article  PubMed  Google Scholar 

  2. Falchetti A, Masi L, Brandi ML (2010) Paget’s disease of bone: there’s more than the affected skeletal—a clinical review and suggestions for the clinical practice. Curr Opin Rheumatol 22:410–423

    Article  PubMed  Google Scholar 

  3. Walsh JP, Ward LC, Stewart GO, Will RK, Criddle RA, Prince RL, Stuckey BG, Dhaliwal SS, Bhagat CI, Retallack RW, Kent GN, Drury PJ, Vasikaran S, Gutteridge DH (2004) A randomized clinical trial comparing oral alendronate and intravenous pamidronate for the treatment of Paget’s disease of bone. Bone 34:747–754

    Article  CAS  PubMed  Google Scholar 

  4. Hosking D, Lyles K, Brown JP, Fraser WD, Miller P, Curiel MD, Devogelaer JP, Hooper M, Su G, Zelenakas K, Pak J, Fashola T, Saidi Y, Eriksen EF, Reid IR (2007) Long-term control of bone turnover in Paget’s disease with zoledronic acid and risedronate. J Bone Miner Res 22:142–148

    Article  CAS  PubMed  Google Scholar 

  5. Reid IR, Miller P, Lyles K, Fraser W, Brown JP, Saidi Y, Mesenbrink P, Su G, Pak J, Zelenakas K, Luchi M, Richardson P, Hosking D (2005) Comparison of a single infusion of zoledronic acid with risedronate for Paget’s disease. N Engl J Med 353:898–908

    Article  CAS  PubMed  Google Scholar 

  6. Miller PD, Brown JP, Siris ES, Hoseyni MS, Axelrod DW, Bekker PJ (1999) A randomized, double-blind comparison of risedronate and etidronate in the treatment of Paget’s disease of bone. Paget’s Risedronate/Etidronate Study Group. Am J Med 106:513–520

    Article  CAS  PubMed  Google Scholar 

  7. Yoh K, Takata S, Yoshimura N, Hashimoto J (2010) Efficacy, tolerability, and safety of risedronate in Japanese patients with Paget’s disease of bone. J Bone Miner Metab 28:468–476

    Article  CAS  PubMed  Google Scholar 

  8. Nishida Y, Yamada Y, Tsukushi S, Sugiura H, Urakawa H, Ishiguro N (2013) Midterm outcome of risedronate therapy for patients with Paget’s disease of bone in the central part of Japan. Clin Rheumatol 32:241–245

    Article  PubMed  Google Scholar 

  9. Selby PL (2006) Guidelines for the diagnosis and management of Paget’s disease: a UK perspective. J Bone Miner Res 21(Suppl 2):P92–P93

    Article  PubMed  Google Scholar 

  10. Reid IR, Davidson JS, Wattie D, Wu F, Lucas J, Gamble GD, Rutland MD, Cundy T (2004) Comparative responses of bone turnover markers to bisphosphonate therapy in Paget’s disease of bone. Bone 35:224–230

    Article  CAS  PubMed  Google Scholar 

  11. Blumsohn A, Naylor KE, Assiri AM, Eastell R (1995) Different responses of biochemical markers of bone resorption to bisphosphonate therapy in Paget disease. Clin Chem 41:1592–1598

    CAS  PubMed  Google Scholar 

  12. Woitge HW, Oberwittler H, Heichel S, Grauer A, Ziegler R, Seibel MJ (2000) Short- and long-term effects of ibandronate treatment on bone turnover in Paget disease of bone. Clin Chem 46:684–690

    CAS  PubMed  Google Scholar 

  13. Selby PL, Davie MW, Ralston SH, Stone MD, Bone, Tooth Society of Great B, National Association for the Relief of Paget’s D (2002) Guidelines on the management of Paget’s disease of bone. Bone 31:366–373

    Article  CAS  PubMed  Google Scholar 

  14. Singer FR (2009) Paget disease: when to treat and when not to treat. Nat Rev Rheumatol 5:483–489

    Article  PubMed  Google Scholar 

  15. Alvarez L, Peris P, Guanabens N, Vidal S, Quinto L, Monegal A, Pons F, Ballesta AM, Munoz-Gomez J (2004) Long-term biochemical response after bisphosphonate therapy in Paget’s disease of bone. Proposed intervals for monitoring treatment. Rheumatology (Oxford) 43:869–874

    Article  CAS  Google Scholar 

  16. Papapoulos SE, Frolich M (1996) Prediction of the outcome of treatment of Paget’s disease of bone with bisphosphonates from short-term changes in the rate of bone resorption. J Clin Endocrinol Metab 81:3993–3997

    CAS  PubMed  Google Scholar 

  17. Randall AG, Kent GN, Garcia-Webb P, Bhagat CI, Pearce DJ, Gutteridge DH, Prince RL, Stewart G, Stuckey B, Will RK, Retallack RW, Price RI, Ward L (1996) Comparison of biochemical markers of bone turnover in Paget disease treated with pamidronate and a proposed model for the relationships between measurements of the different forms of pyridinoline cross-links. J Bone Miner Res 11:1176–1184

    Article  CAS  PubMed  Google Scholar 

  18. Alexandersen P, Peris P, Guanabens N, Byrjalsen I, Alvarez L, Solberg H, Cloos PA (2005) Non-isomerized C-telopeptide fragments are highly sensitive markers for monitoring disease activity and treatment efficacy in Paget’s disease of bone. J Bone Miner Res 20:588–595

    Article  CAS  PubMed  Google Scholar 

  19. Cacace E, Ruggiero V, Matulli C, Uras L, Perpignano G (2004) Markers of bone resorption in bisphosphonate therapy of Paget’s disease. Clin Exp Rheumatol 22:502

    CAS  PubMed  Google Scholar 

  20. Takata S, Hashimoto J, Nakatsuka K, Yoshimura N, Yoh K, Ohno I, Yabe H, Abe S, Fukunaga M, Terada M, Zamma M, Ralston SH, Morii H, Yoshikawa H (2006) Guidelines for diagnosis and management of Paget’s disease of bone in Japan. J Bone Miner Metab 24:359–367

    Article  PubMed  Google Scholar 

  21. Patel S, Stone MD, Coupland C, Hosking DJ (1993) Determinants of remission of Paget’s disease of bone. J Bone Miner Res 8:1467–1473

    Article  CAS  PubMed  Google Scholar 

  22. Joshua F, Epstein M, Major G (2003) Bisphosphonate resistance in Paget’s disease of bone. Arthritis Rheum 48:2321–2323

    Article  CAS  PubMed  Google Scholar 

  23. Papapoulos SE, Eekhoff EM, Zwinderman AH (2006) Acquired resistance to bisphosphonates in Paget’s disease of bone. J Bone Miner Res 21(Suppl 2):P88–P91

    Article  CAS  PubMed  Google Scholar 

  24. Harinck HI, Bijvoet OL, Vellenga CJ, Blanksma HJ, Frijlink WB (1986) Relation between signs and symptoms in Paget’s disease of bone. Q J Med 58:133–151

    CAS  PubMed  Google Scholar 

  25. Meunier PJ, Salson C, Mathieu L, Chapuy MC, Delmas P, Alexandre C, Charhon S (1987) Skeletal distribution and biochemical parameters of Paget’s disease. Clin Orthop Relat Res 217:37–44

  26. Alvarez L, Peris P, Pons F, Guanabens N, Herranz R, Monegal A, Bedini JL, Deulofeu R, Martinez de Osaba MJ, Munoz-Gomez J, Ballesta AM (1997) Relationship between biochemical markers of bone turnover and bone scintigraphic indices in assessment of Paget’s disease activity. Arthritis Rheum 40:461–468

    Article  CAS  PubMed  Google Scholar 

  27. Peris P, Alvarez L, Vidal S, Kasper D, Leeming DJ, Monegal A, Angeles Martinez M, Pons F, Guanabens N (2006) Biochemical response to bisphosphonate therapy in pagetic patients with skull involvement. Calcif Tissue Int 79:22–26

    Article  CAS  PubMed  Google Scholar 

  28. Civitelli R, Armamento-Villareal R, Napoli N (2009) Bone turnover markers: understanding their value in clinical trials and clinical practice. Osteoporos Int 20:843–851

    Article  CAS  PubMed  Google Scholar 

  29. Tsujimoto M, Chen P, Miyauchi A, Sowa H, Krege JH (2011) PINP as an aid for monitoring patients treated with teriparatide. Bone 48:798–803

    Article  CAS  PubMed  Google Scholar 

  30. Ralston SH, Layfield R (2012) Pathogenesis of Paget disease of bone. Calcif Tissue Int 91:97–113

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

We would like to express our appreciation to Ajinomoto Pharmaceuticals Co., Ltd. for permitting the use of part of the Phase III data for oral risedronate treatment. This work was supported in part by Grants-in-Aid Scientific Research (C) (No. 24591235 to YI) and (No. 24591353 to MI and YI) from the Ministry of Science, Education and Culture of Japan.

Conflict of interests

YI, MI and TM received lecture fees and unrestricted research grants from Takeda Pharmaceutical Company Limited and Eisai Co. Ltd.

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Authors and Affiliations

  1. Department of Metabolism, Endocrinology, and Molecular Medicine, Osaka City University Graduate School of Medicine, 1-4-3, Asahi-machi, Abeno-Ku, Osaka, 545-8585, Japan

    Masaya Ohara, Yasuo Imanishi, Yuki Nagata, Ikue Kobayashi, Katsuhito Mori, Yoshiki Nishizawa & Masaaki Inaba

  2. Department of Physiology, Osaka City University Graduate School of Medicine, Osaka, Japan

    Akira Ishii

  3. Department of Geriatrics and Neurology, Osaka City University Graduate School of Medicine, Osaka, Japan

    Takami Miki

  4. Department of Orthopaedics, Hokkaido University School of Medicine, Sapporo, Japan

    Manabu Ito

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  1. Masaya Ohara
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  2. Yasuo Imanishi
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  3. Yuki Nagata
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  4. Akira Ishii
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  7. Manabu Ito
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Correspondence to Yasuo Imanishi.

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Ohara, M., Imanishi, Y., Nagata, Y. et al. Clinical efficacy of oral risedronate therapy in Japanese patients with Paget’s disease of bone. J Bone Miner Metab 33, 584–590 (2015). https://doi.org/10.1007/s00774-014-0623-5

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  • DOI: https://doi.org/10.1007/s00774-014-0623-5

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