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Treatment of Patients with Paget’s Disease of Bone

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Abstract

Paget’s disease is a progressive bone disease, monostotic or polyostotic, characterised by hypertrophy of affected bones and accelerated disorganised bone remodelling. It results in bone deformities and pain, with a risk for articular and neurological complications, and fractures. The risk of complications, and thus the therapeutic decision, is a function of the age of the patient, and the severity and the activity of the disease. Bisphosphonates are first-line therapy for Paget’s disease, and the advent of the new bisphosphonates permits a dramatic improvement in treatment. The optimal treatment regimen should obtain normalisation or quasi-normalisation of markers of bone remodelling. This result has the potential for a long-term control of the disease.

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References

  1. Delmas PD, Meunier PJ. The management of Paget’s disease of bone. N Engl J Med 1997; 336: 559–66

    Google Scholar 

  2. Hosking D, Meunier PJ, Ringe JD, et al. Paget’s disease of bone: diagnosis and management. BMJ 1996; 312: 491–4

    Article  PubMed  CAS  Google Scholar 

  3. Detheridge FM, Guyer PB, Barker DJP European distribution of Paget’s disease of bone. BMJ 1982; 285: 1005–8

    Article  PubMed  CAS  Google Scholar 

  4. Renier JC, Fanello S, Rodriguez N, et al. Current prevalence of Paget’s disease of bone in a region of France [Anjou]. Rev Rheum 1995; 65: 571–5

    Google Scholar 

  5. Magen H, Liel Y, Bearman JE, et al. Demographic aspects of Paget’s disease of bone in the Negev of Southern Israel. Calcif Tissue Int 1994; 55: 353–5

    Article  PubMed  CAS  Google Scholar 

  6. Cundy T, McAnulty K, Wattie D, et al. Evidence for secular change in Paget’s disease. Bone 1997; 20: 69–71

    Article  PubMed  CAS  Google Scholar 

  7. Siris ES. Paget’s disease of bone. J Bone Miner Res 1998; 13: 1061–5

    Article  PubMed  CAS  Google Scholar 

  8. Siris ES, Ottman R, Flaster E, et al. Familial aggregation of Paget disease of bone. J Bone Miner Res 1991; 6: 495–500

    Article  PubMed  CAS  Google Scholar 

  9. Morales-Piga AA, Rey-Rey JS, Corres-Conzalez J, et al. Frequency and characteristics of familial aggregation of Paget’s disease of bone. J Bone Miner Res 1995; 10: 663–70

    Article  PubMed  CAS  Google Scholar 

  10. Haslam SI, Van Hul W, Morales-Piga A, et al. Paget’s disease of bone: evidence for a susceptibility locus on chromosome 18q and for genetic heterogeneity. J Bone Miner Res 1998; 13: 911–7

    Article  PubMed  CAS  Google Scholar 

  11. Rebel A, Malkami K, Basle J. Anomalies nucléaires des ostéoclastes de la maladie de Paget. Nouv Presse Med 1974; 3: 1299–301

    PubMed  CAS  Google Scholar 

  12. Rebel A, Baslé MF, Pouplard A. Viral antigens in osteoclasts from Paget’s disease of bone. Lancet 1980; 2: 344–6

    Article  PubMed  CAS  Google Scholar 

  13. Baslé MF, Fournier JG, Rozenblatt S, et al. Measles virus RNA detected in Paget’s disease bone tissue by in situ hybridization. J Gen Virol 1986; 67: 907–13

    Article  PubMed  Google Scholar 

  14. Khan SA, Brennan P, Newman J, et al. Paget’s disease of bone and unvaccinated dogs. Bone 1996; 19: 47–50

    Article  PubMed  CAS  Google Scholar 

  15. Birch MA, Taylor W, Fraser WD, et al. Absence of paraxmyxovirus RNA in cultures of pagetic bone cells and in pagetic bone. J Bone Miner Res 1994; 9: 11–6

    Article  PubMed  CAS  Google Scholar 

  16. Reddy SV, Singer FR, Mallette L, et al. Detection of measles virus nucleocapsid transcripts in circulating blood cells from patients with Paget disease. J Bone Miner Res 1996; 11: 1602–7

    Article  PubMed  CAS  Google Scholar 

  17. Hoyland JA, Freemont AJ, Sharpe PT. Interleukin 6, IL6 receptor and IL6 nuclear factor gene expression in Paget’s disease. J Bone Miner Res 1994; 9: 75–80

    Article  PubMed  CAS  Google Scholar 

  18. Patel S, Lyons AR, Hosking DJ. Drugs used in the treatment of metabolic bone diseases Drugs 1993; 46: 594–627

    Article  PubMed  CAS  Google Scholar 

  19. Helliwell PS. Osteoarthritis and Paget’s disease. Br J Rheum 1995; 34: 1061–3

    Article  CAS  Google Scholar 

  20. Meunier PJ, Vignot E. Therapeutic strategy in Paget’s disease of bone. Bone 1995; 17 Suppl: 489S–91S

    Article  PubMed  CAS  Google Scholar 

  21. Monsell EM, Bone HG, Cody DD, et al. Hearing loss in Paget’s disease of bone: evidence of auditory nerve integrity. Am J Otol 1995; 16: 27–33

    PubMed  CAS  Google Scholar 

  22. Gold DT, Boisture J, Shipp KM, et al. Paget’s disease of bone and quality of life. J Bone Miner Res 1996; 11: 1897–904

    Article  PubMed  CAS  Google Scholar 

  23. Dodd GW, Ibbertson HK, Fraser TRC, et al. Radiological assessment of Paget’s disease of bone after treatment with the bisphosphonates EHDP and APD. Br J Radiol 1987; 60: 849–60

    Article  PubMed  CAS  Google Scholar 

  24. Murphy WA, Whyte MP, Haddad JG. Paget bone disease: radiological documentation of healing with human calcitonin therapy. Radiology 1980; 136: 1–4

    PubMed  CAS  Google Scholar 

  25. Devogelaer JP, Malghem J, Stasse P, et al. Biological and radiological responses to oral etidronate and tiludronate in Paget’s disease of bone. Bone 1997; 20: 259–61

    Article  PubMed  CAS  Google Scholar 

  26. Siris E, Weinstein RS, Altman R, et al. Comparative study of alendronate versus etidronate for the treatment of Paget’s disease of bone. J Clin Endocrinol Metab 1996; 81: 961–7

    Article  PubMed  CAS  Google Scholar 

  27. Patel S, Pearson D, Hosking DJ. Quantitative bone scintigraphy in the management of monostotic Paget’s disease of bone. Arthritis Rheum 1995; 38: 1506–12

    Article  PubMed  CAS  Google Scholar 

  28. Kanis JA, Gray RE. Long term follow-up observations on treatment in Paget’s disease of bone. Clin Orthop 1987; 217: 99–125

    PubMed  Google Scholar 

  29. Walton RJ, Preston CJ, Bartlett M, et al. Biochemical measurements in Paget’s disease of bone. Eur J Clin Invest 1977; 7: 37–9

    Article  PubMed  CAS  Google Scholar 

  30. Alvarez L, Peris P, Pons F, et al. Relationship between biochemical markers of bone turnover and bone scintigraphic indices in assessment of Paget’s disease activity. Arthritis Rheum 1997; 40: 461–8

    Article  PubMed  CAS  Google Scholar 

  31. Delmas PD, Demiaux B, Malaval L, et al. Serum bone GLA-protein is not a sensitive marker of bone turnover in Paget’s disease of bone. Calcif Tissue Int 1986; 38: 60–1

    Article  PubMed  CAS  Google Scholar 

  32. Alvarez L, Guanabens N, Peris P, et al. Discriminative value of biochemical markers of bone turnover in assessing the activity of Paget’s disease. J Bone Miner Res 1995; 10: 458–65

    Article  PubMed  CAS  Google Scholar 

  33. Randall AG, Kent GM, Garcia-Webb P, et al. 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 crosslinks. J Bone Miner Res 1996; 11: 1176–84

    Article  PubMed  CAS  Google Scholar 

  34. Garnero P, Fledelius C, Gineyts E, et al. Decreased β-isomerization of the C-terminal telopeptide of type I collagen α1 chain in Paget’s disease of bone. J Bone Miner Res 1997; 12: 1407–15

    Article  PubMed  CAS  Google Scholar 

  35. Delmas PD, Chapuy MC, Edouard C, et al. Beneficial effects of aminohexane diphosphonate in patients with Paget’s disease of bone resistant to sodium etidronate. Am J Med 1987; 83: 276–82

    Article  PubMed  CAS  Google Scholar 

  36. Yates AJP, Percival RC, Gray RES, et al. Intravenous clodronate in the treatment and retreatment of Paget’s disease of bone. Lancet 1985; 1: 1474–7

    Article  PubMed  CAS  Google Scholar 

  37. Coutris G, Cayla J, Roudier J, et al. Analyse des pertubations des voies principales du métabolisme calcique dans la maladie de Paget.: effects de l’administration de calcitonine. Rev Rhum Mal Osteoartic 1975; 42: 759–67

    PubMed  CAS  Google Scholar 

  38. Renier JC, Cronier P, Audran M. Nouvel index anatomique, établi sur des bases actuelles, pour calculer notament le pourcentage d’os pagétique sur un squelette. Rev Rhum Ed Fr 1995; 62: 373–7

    Google Scholar 

  39. Alexandre CM, Chapuy MC, Vignon E, et al. Treatment of Paget’s disease of bone with ethane-1, hydroxy-1, 1 diphosphonate (EHDP) at a low dosage (5 mg/Kg/day). Clin Orthop Res 1983; 174: 193–205

    Google Scholar 

  40. Meunier PJ, Ravault A. Treatment of Paget’s disease with etidronate disodium. In: Singer RF, Wallach S, editors. Paget’s disease of bone: clinical assessment, present and future therapy. New York: Elsevier 1991: 86–99

    Google Scholar 

  41. Altman RD. Long term follow-up of therapy with an intermittent etidronate disodium in Paget’s disease of bone. Am J Med 1985; 79: 583–90

    Article  PubMed  CAS  Google Scholar 

  42. Johnston CC, Khairi MRA, Meunier PJ. Use of etidronate (EHDP) in Paget’s disease of bone. Arthritis Rheum 1980; 23: 1172–6

    Article  PubMed  Google Scholar 

  43. Siris ES, Canfield RE, Jacobs TP, et al. Long-term therapy of Paget’s disease of bone with EHDP. Arthritis Rheum 1980; 23: 1177–84

    Article  PubMed  CAS  Google Scholar 

  44. Canfield R, Rosner W, Skinner J, et al. Diphosphonate therapy of Paget’s disease of bone. J Clin Endocrinol Metab 1977; 44: 96–106

    Article  PubMed  CAS  Google Scholar 

  45. Johnston Jr CC, Altman RD, Canfield RE, et al. Review of fracture experience during treatment of Paget’s disease of bone with etidronate disodium (EHDP). Clin Orthop 1983; 172: 186–94

    PubMed  Google Scholar 

  46. Gray RES, Yates AJP, Preston CJ, et al. Duration of effect of oral diphosphonate therapy in Paget’s disease of bone. Q J Med 1987; 64: 755–67

    PubMed  CAS  Google Scholar 

  47. Douglas DL, Duckworth T, Kanis JA, et al. Biochemical and clinical responses to dichloromethylene diphosphonate (CL2MDP) in Paget’s disease of bone. Arthritis Rheum 1980; 23: 1185–92

    Article  PubMed  CAS  Google Scholar 

  48. Delmas PD, Chapuy MC, Vigon E, et al. Long-term effects of dichloromethylene diphosphonate in Paget’s disease of bone. J Clin Endocrinol Metab 1982; 54: 837–44

    Article  PubMed  CAS  Google Scholar 

  49. Khan SA, Mc Closkey EV, Eyres KS, et al. Comparison of three intravenous regimens of clodronate in Paget disease of bone. J Bone Miner Res 1996; 11: 178–82

    Article  PubMed  CAS  Google Scholar 

  50. Mautalen CA, Casco CA, Gonzalez D, et al. Side-effects of disodium aminohydroxy-propylidene diphosphonate (APD) during treatment of bone diseases. Br Med J (Clin Res Ed) 1984; 288: 828–9

    Article  CAS  Google Scholar 

  51. Cantrill JA, Buckler HM, Anderson DC. Low dose intravenous 3-amino-l-hydoxypropylidene-l, 1-bisphosphonate (APD) for treatment of Paget’s disease of bone. Ann Rheum Dis 1986; 45: 1012–8

    Article  PubMed  CAS  Google Scholar 

  52. Vega E, Gonzalez D, Ghiringhelli G. Intravenous aminopropylidene, bisphosphonate (ADP) in the treatment of Paget’s disease. J Bone Miner Res 1987; 2: 267–71

    Article  PubMed  CAS  Google Scholar 

  53. Thiebaud D, Jaeger P, Gobelet C, et al. Single infusion of the bisphosphonate AHPrBP (APD) as treatment of Paget’s disease of bone. Am J Med 1988; 85: 207–12

    Article  PubMed  CAS  Google Scholar 

  54. Ryan PJ, Sherry M, Gobson T, et al. Treatment of Paget’s disease by weekly infusions of 3-aminohydroxypylidene-l, 1-bisphosphonate (ADP). Br J Rheum 1992; 31: 97–101

    Article  CAS  Google Scholar 

  55. Siris ES. Bisphosphonates and iritis. Lancet 1993; 341: 436–7

    Article  PubMed  CAS  Google Scholar 

  56. Adamson BB, Gallacher SJ, Byars J, et al. Mineralisation defects with pamidronate therapy for Paget’s disease. Lancet 1993; 342: 1459–60

    Article  PubMed  CAS  Google Scholar 

  57. Arden-Cardone M, Siris ES, Lyles KW, et al. Antiresorptive effect of a single infusion of microgram quantities of zoled-ronate in Paget’s disease of bone. Calcif Tissue Int 1997; 60: 415–8

    Article  Google Scholar 

  58. Garnero P, Gineyts E, Schaffer AV, et al. Measurement of urinary excretion of non-isomerized and beta-isomerised forms of type I collagen breakdown products to monitor the effects of the bisphosphonate zoledronate in Paget’s disease. Arthritis Rheum 1998; 354–60

  59. Audran M, Clochon P, Ethgen D, et al. Treatment of Paget’s disease of bone with (4-chloro-phenyl) thiomethylene bisphosphonate. Clin Rheum 1989; 8: 71–9

    Article  CAS  Google Scholar 

  60. Reginster JY, Colson F, Morlock G, et al. Evaluation of the efficacy and safety of oral tiludronate in Paget’s disease of bone. Arthritis Rheum 1992; 35: 967–74

    Article  PubMed  CAS  Google Scholar 

  61. Reginster JY, Lecart MP, Deroisy R, et al. Paget’s disease of bone treated with a five day course of oral tiludronate. Ann Rheum Dis 1993; 52: 54–7

    Article  PubMed  CAS  Google Scholar 

  62. Roux C, Gennari C, Farrerons J, et al. Comparative prospective double-blind multicenter study of the efficacy of tiludronate and etidronate in the treatment of Paget’s disease of bone. Arthritis Rheum 1995; 38: 851–8

    Article  PubMed  CAS  Google Scholar 

  63. Reid IR, Nicholson GC, Weinstein RS, et al. Biochemical and radiologic improvement in Paget’s disease of bone treated with alendronate: a randomized placebo-controlled trial. Am J Med 1996; 171: 341–8

    Article  Google Scholar 

  64. Singer FR, Clemens TL, Ensebio RA, et al. Risedronate, a highly effective oral agent in the treatment of patients with severe Paget’s disease. J Clin Endocrinol Metab 1998; 83: 1906–10

    Article  PubMed  CAS  Google Scholar 

  65. Siris ES, Chines AA, Airman RD, et al. Risedronate in the treatment of Paget’s disease of bone: an open label multicenter study. J Bone Miner Res 1998; 13: 1032–8

    Article  PubMed  CAS  Google Scholar 

  66. De Groen PC, Lubbe DF, Hirsch LJ, et al. Esophagitis associated with the use of alendronate. N Engl J Med 1996; 335: 1016–21

    Article  PubMed  Google Scholar 

  67. Kanis JA, Horn DB, Scott RDM, et al. Treatment of Paget’s disease of bone with synthetic salmon calcitonin. BMJ 1974; 3: 727–31

    Article  PubMed  CAS  Google Scholar 

  68. Greenberg PB, Doyle FH, Fisher HT. Treatment of Paget’s disease of bone with synthetic human calcitonin. Am J Med 1974; 56: 867–71

    Article  PubMed  CAS  Google Scholar 

  69. Reginster JY, Jeugmans-Hyunen AM, Albert A, et al. One year’s treatment of Paget’s disease of bone by synthetic salmon calcitonin as a nasal spray. J Bone Miner Res 1988; 3: 249–52

    Article  PubMed  CAS  Google Scholar 

  70. Reginster JY, Denis D, Albert A, et al. Assessment of the biological effectiveness of nasal synthetic salmon calcitonin (SSCT) by comparison with intramuscular (i.m.) or placebo injection in normal subjects. Bone Miner 1987; 2: 133–40

    PubMed  CAS  Google Scholar 

  71. Haddad JG, Caldwell JG. Calcitonin resistance: clinical and immunologic studies in subjects with Paget’s disease of bone treated with porcine and salmon calcitonin. J Clin Invest 1972; 51: 3133–41

    Article  PubMed  Google Scholar 

  72. Grauer A, Raue F, Schneider HG, et al. In vitro detection of neutralizing antibodies after treatment of Paget’s disease of bone with nasal salmon calcitonin. J Bone Miner Res 1990; 10: 243–52

    Article  Google Scholar 

  73. Levy F, Muff R, Dotti-Sigrist S, et al. Formation of neutralizing antibodies during intranasal synthetic salmon calcitonin treatment of Paget’s disease of bone. J Clin Endocrinol Metab 1990; 67: 541–5

    Article  Google Scholar 

  74. Bouizar Z, Rostene WH, Milhaud G. Down-regulation of rat kidney calcitonin receptors by salmon calcitonin infusion evidenced by autoradiography. Proc Natl Acad Sci U S A 1987; 84: 5125–8

    Article  PubMed  CAS  Google Scholar 

  75. Matkovic V, Apseloff G, Shepard DR, et al. Use of gallium to treat Paget’s disease of bone: a pilot study. Lancet 1990; 335: 72–5

    Article  PubMed  CAS  Google Scholar 

  76. Warrel RP, Bosco B, Weinerman S, et al. Gallium nitrate for advanced Paget’s disease of bone: effectiveness and dose-response analysis. Ann Intern Med 1991; 113: 847–51

    Google Scholar 

  77. Bockman RS, Wilhem F, Siris E, et al. A multicenter trial of low dose gallium nitrate in patients with advanced Paget’s disease of bone. J Clin Endocrinol Metab 1995; 80: 595–602

    Article  PubMed  CAS  Google Scholar 

  78. Patel S. Treatment response in Paget’s disease. Ann Rheum Dis 1995; 54: 783–4

    Article  PubMed  CAS  Google Scholar 

  79. Patel S, Stone MD, Coupland C, et al. Determinants of remission of Paget’s disease of bone. J Bone Miner Res 1993; 8: 1467–73

    Article  PubMed  CAS  Google Scholar 

  80. Cundy T, Wattie D, King AR. High dose pamidronate in the management of resistant Paget’s disease. Calcif Tissue Int 1996; 58: 6–8

    Article  PubMed  CAS  Google Scholar 

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  1. Centre d’Evaluation des Maladies Osseuses, Department of Rheumatologie, Hôpital Cochin, Assistance Publique-Hopitaux de Paris, Université René Descartes, 27 rue du Faubourg St Jacques, 75014, Paris, France

    Christian Roux & Maxime Dougados

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Roux, C., Dougados, M. Treatment of Patients with Paget’s Disease of Bone. Drugs 58, 823–830 (1999). https://doi.org/10.2165/00003495-199958050-00005

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