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Endocrine

, Volume 63, Issue 3, pp 651–656 | Cite as

Long-term control of Paget’s disease of bone with low-dose, once-weekly, oral bisphosphonate preparations, in a “real world” setting

  • Yair LielEmail author
  • Muhammad Abu Tailakh
Original Article

Abstract

Purpose

Bisphosphonates are the mainstay of the treatment of Paget’s disease of bone (PDB). Clinical practice guidelines recommend treatment with intravenous zoledronic acid or high-dose oral nitrogen bisphosphonates (N-BPs). We present our long-term experience treating PDB patients with lower than recommended oral doses of N-BPs, equivalent to once-weekly doses used for treating osteoporosis.

Methods

PDB patients were seen, between 1990 and 2015 at the endocrine clinic of an academic medical center. Diagnosis was established according to accepted criteria. Patients were initially treated with alendronate 70 mg/week or risedronate 35 mg/week. Whenever the initial dose failed to produce remission, the dosage was increased to twice a week the respective dose.

Results

Patients were followed for a mean of 11.9 years (range: 1.7–24.8). Out of 96 treatment courses with N-BPs, 89% were with alendronate and 11% with risedronate. Remission was achieved in 84% of the courses with alendronate 70 mg/week. 90% of those who did not achieve remission subsequently responded to 140 mg/week. Out of the 8 treatment courses with risedronate 35 mg/week, 87% achieved remission, and the 2 patients who did not achieve remission subsequently responded to 70 mg/week. The median duration of remissions following 3-4 months courses of alendronate 70 mg/week or risedronate 35 mg/week was 8.8 months (IQR: 5.5, 14.8).

Conclusion

In a large proportion of “real world” PDB patients, remission can be achieved with once-weekly, “osteoporosis doses” of alendronate or risedronate.

Keywords

Paget’s disease of bone Bisphosphonates Alendronate Risedronate 

Notes

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Informed consent

The study protocol was approved by the Soroka Medical Center Human Research Review Board in accordance with the Declaration of Helsinki. For this type of study formal consent is not required.

References

  1. 1.
    S. Takata, J. Hashimoto, K. Nakatsuka, N. Yoshimura, K. Yoh, I. Ohno et al. Guidelines for diagnosis and management of Paget’s disease of bone in Japan. J. Bone Miner. Metab. 24, 359–367 (2006)CrossRefPubMedGoogle Scholar
  2. 2.
    J.P. Devogelaer, P. Bergmann, J.J. Body, Y. Boutsen, S. Goemaere, J.M. Kaufman et al. Management of patients with Paget’s disease: a consensus document of the Belgian Bone Club. Osteoporos. Int. 19, 1109–1117 (2008)CrossRefPubMedGoogle Scholar
  3. 3.
    E.S Siris, G.D Roodman. Paget’s disease of bone. In Primer on the metabolic bone diseases and disorders of mineral metabolism, ed by Rosen C.J, Bouillon R., Compston J.E., Rosen V. 8 edn. (Wiley-Blackwell, Danvers, MA, 2013) pp. 659-668.Google Scholar
  4. 4.
    F.R. Singer, H.G. Bone, D.J. Hosking, K.W. Lyles, M.H. Murad, I.R. Reid et al. Paget’s disease of bone: an endocrine society clinical practice guideline. J. Clin. Endocrinol. Metab. 99, 4408–4422 (2014)CrossRefPubMedGoogle Scholar
  5. 5.
    C. Muschitz, X. Feichtinger, J. Haschka, R. Kocijan, Diagnosis and treatment of Paget’s disease of bone: a clinical practice guideline. Wien. Med. Wochenschr. 167, 18–24 (2017)CrossRefPubMedGoogle Scholar
  6. 6.
    M. Hoshiro, T. Harada, H. Iwai, T. Miyatake, A. Nishimura, Y. Ohno et al. Two cases of monostotic Paget’s disease: effects of bisphosphonate. Endocr. J. 50, 385–392 (2003)CrossRefPubMedGoogle Scholar
  7. 7.
    J. Takada, K. Iba, T. Yamashita, Low dose of oral alendronate decreases bone turnover in Japanese patients with Paget’s disease of bone. J. Bone Miner. Metab. 23, 333–336 (2005)CrossRefPubMedGoogle Scholar
  8. 8.
    Anjali, N. Thomas, S. Rajaratnam, N. Shanthly, R. Oommen, M.S. Seshadri, Paget’s disease of bone: experience from a centre in southern India. J. Assoc. Physicians India 54, 525–529 (2006)PubMedGoogle Scholar
  9. 9.
    J.P. Walsh, R. Attewell, B.G. Stuckey, M.J. Hooper, J.D. Wark, S. Fletcher et al. Treatment of Paget’s disease of bone: a survey of clinical practice in Australia. Bone 42, 1219–1225 (2008)CrossRefPubMedGoogle Scholar
  10. 10.
    R.D. Altman, Long-term follow-up of therapy with intermittent etidronate disodium in Paget’s disease of bone. Am. J. Med. 79, 583–590 (1985)CrossRefPubMedGoogle Scholar
  11. 11.
    S. Adami, M. Mian, P. Gatti, M. Rossini, N. Zamberlan, F. Bertoldo et al. Effects of two oral doses of alendronate in the treatment of Paget’s disease of bone. Bone 15, 415–417 (1994)CrossRefPubMedGoogle Scholar
  12. 12.
    S.A. Khan, S. Vasikaran, E.V. McCloskey, M.N. Beneton, S. Rogers, L. Coulton et al. Alendronate in the treatment of Paget’s disease of bone. Bone 20, 263–271 (1997)CrossRefPubMedGoogle Scholar
  13. 13.
    J.P. Brown, D.J. Hosking, L. Ste-Marie, C.C.J. Johnston, J. Reginster, W.G. Ryan et al. Risedronate, a highly effective, short-term oral treatment for Paget’s disease: a dose-response study. Calcif. Tissue Int. 64, 93–99 (1999)CrossRefPubMedGoogle Scholar
  14. 14.
    K. Iba, J. Takada, T. Wada, T. Yamashita, Five-year follow-up of Japanese patients with Paget’s disease of the bone after treatment with low-dose oral alendronate: a case series. J. Med. Case Rep. 4, 166 (2010)CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    J.R. Hampton, Evidence-based medicine, opinion-based medicine, and real-world medicine. Perspect. Biol. Med. 45, 549–568 (2002)CrossRefPubMedGoogle Scholar
  16. 16.
    I.R. Reid, D.J. Hosking, Bisphosphonates in Paget’s disease. Bone 49, 89–94 (2011)CrossRefPubMedGoogle Scholar
  17. 17.
    R.E. Gray, A.J. Yates, C.J. Preston, R. Smith, R.G. Russell, J.A. Kanis, Duration of effect of oral diphosphonate therapy in Paget’s disease of bone. Q. J. Med. 64, 755–767 (1987)PubMedGoogle Scholar
  18. 18.
    S.A. Khan, E.V. McCloskey, K. Nakatsuka, J. Orgee, G.M. Coombes, J.A. Kanis, Duration of response with oral clodronate in Paget’s disease of bone. Bone 18, 185–190 (1996)CrossRefPubMedGoogle Scholar
  19. 19.
    Y. Liel, Y. Plakht, M. Abu Tailakh, Bone turnover in osteoporotic women during long-term oral bisphosphonates treatment. Implications for treatment failure and "drug holiday" in the real world. Endocr. Pract 23, 787–793 (2017).CrossRefPubMedGoogle Scholar
  20. 20.
    S.H. Ralston, L. Corral-Gudino, W.D. Fraser, L. Gennari, N. Guañabens, P.L. Selby, Letter to the Editor: the endocrine society clinical practice guidelines on Paget’s disease: many recommendations are not evidence based. J. Clin. Endocrinol. Metab. 100, L45–L46 (2015)CrossRefPubMedGoogle Scholar
  21. 21.
    A.L. Langston, M.K. Campbell, W.D. Fraser, G.S. MacLennan, P.L. Selby, S.H. Ralston et al. Randomized trial of intensive bisphosphonate treatment versus symptomatic management in Paget’s disease of bone. J. Bone Miner. Res. 25, 20–31 (2010)CrossRefPubMedGoogle Scholar
  22. 22.
    A. Tan, K. Goodman, A. Walker, J. Hudson, G.S. MacLennan, P.L. Selby et al. Long-term randomized trial of intensive versus symptomatic management in Paget’s disease of bone: The PRISM-EZ Study. J. Bone Miner. Res. 32, 1165–1173 (2017)CrossRefPubMedGoogle Scholar
  23. 23.
    A.A. Al Nofal, O. Altayar, K. BenKhadra, O.Q. Qasim Agha, N. Asi, M. Nabhan et al. Bone turnover markers in Paget’s disease of the bone: A Systematic review and meta-analysis. Osteoporos. Int. 26, 1875–1891 (2015)CrossRefPubMedGoogle Scholar
  24. 24.
    F.H. Ebetino, A.M. Hogan, S. Sun, M.K. Tsoumpra, X. Duan, J.T. Triffitt et al. The relationship between the chemistry and biological activity of the bisphosphonates. Bone 49, 20–33 (2011)CrossRefPubMedGoogle Scholar
  25. 25.
    P. Peris, M. Torra, V. Olivares, R. Reyes, A. Monegal, A. Martínez-Ferrer et al. Prolonged bisphosphonate release after treatment in women with osteoporosis. Relatsh. Bone Turnover Bone 49, 706–709 (2011)Google Scholar
  26. 26.
    R. Eastell, R.A. Hannon, D. Wenderoth, J. Rodriguez-Moreno, A. Sawicki, Effect of stopping risedronate after long-term treatment on bone turnover. J. Clin. Endocrinol. Metab. 96, 3367–3373 (2011)CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    T. Cundy, Treating Paget’s disease-why and how much? J. Bone Miner. Res. 32, 1163–1164 (2017)CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Internal Medicine, Soroka University Medical Center and Faculty of Health SciencesBen-Gurion University of the NegevBeer-ShevaIsrael
  2. 2.Nursing Research Unit, Soroka University Medical Center and Faculty of Health SciencesBen-Gurion University of the NegevBeer-ShevaIsrael

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