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Paget’s disease of bone: Diagnosis and treatment update

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Abstract

Paget’s disease is a metabolic bone disease characterized by excessive bone resorption and formation due to activated osteoclasts. Although Paget’s disease is a high bone turnover state, the excess bone that is formed lacks the structural stability of normal bone. Complications from Paget’s disease include deformity, fracture, and pain. Although still unclear, both prevalence and severity of Paget’s disease seem to be declining. Recent progress has focused on the environmental as well as genetic etiologies for this disease. Many studies indicate a role for viral infectious agents, whereas others point to a recently identified candidate gene on chromosome 18q. Therapy with bisphosphonate drugs is the treatment of choice. With newer and more powerful agents from this family now available, the majority of patients affected by Paget’s disease can achieve sustained remission and avoid complications.

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References and Recommended Reading

  1. Paget J: On a form of chronic inflammation of bones (osteitis deformans). Med-Chir Transactions of London 1877, 60:37–64.

    Google Scholar 

  2. Kaplan FS: Paget’s disease of bone: exploring the questions. Calcified Tissue Intern 1992, 51:1–3.

    Article  CAS  Google Scholar 

  3. Guyer PB, Chamberlain AT: Paget’s disease of bone in two American cities. BMJ 1980, 280:985.

    Article  PubMed  CAS  Google Scholar 

  4. Siris ES: Epidemiological aspects of Paget’s disease: family history and relationship to other medical conditions. Seminars Arthritis Rheum 1994, 23:222–225.

    Article  CAS  Google Scholar 

  5. Kanis JA: Pathophysiology and treatment of paget’s disease of bone. London: Dunitz, 1991.

    Google Scholar 

  6. Jaffe H: Paget’s disease of bone: Arch Pathol 1933, 15:83.

    CAS  Google Scholar 

  7. Mirra JM, Brien EW, Tehranzadeh J: Paget’s disease of bone: review with emphasis on radiologic features, Part I. Skeletal Radiol 1995, 24:163–71. A thorough review of the spectrum of radiographic findings in Paget’s disease in 2 parts.

    PubMed  CAS  Google Scholar 

  8. Epstein BS, Epstein JA: The association of cerebellar tonsillar herniation with basilar impression incident to Paget’s disease. Am J Roentgenol, Rad Therapy Nucl Med 1969, 107:535–542.

    CAS  Google Scholar 

  9. Sadar ES, Walton RJ, Gossman H: Neurological dysfunction in Paget’s disease of the vertebral column. J Neurosurg 1972, 37:661–665.

    Article  PubMed  CAS  Google Scholar 

  10. Wick MR, Siegal GP, Unni KK, et al.: Sarcomas of bone complicating osteitis deformans Paget’s disease: fifty years’ experience. Am J Surg Pathol 1981, 5:47–59.

    Article  PubMed  CAS  Google Scholar 

  11. Mirra JM, Brien EW, Tehranzadeh J: Paget’s disease of bone: review with emphasis on radiologic features, Part II. Skeletal Radiol 1995, 24:173–184. A thorough review of the spectrum of radiographic findings in Paget’s disease in 2 parts.

    PubMed  CAS  Google Scholar 

  12. Alvarez L, Guaanabens 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, 10:458–465.

    PubMed  CAS  Google Scholar 

  13. Siris ES, Clemens TP, McMahon D, et al.: Parathyroid function in Paget’s disease of bone. J Bone Min Res 1989, 4:75–79.

    CAS  Google Scholar 

  14. Bahk YW, Park YH, Chung SK, Chi JG: Bone pathologic correlation of multimodality imaging in Paget’s disease. J Nucl Med 1995, 36:1421–1426.

    PubMed  CAS  Google Scholar 

  15. Kaufmann GA, Sundaram M, McDonald DJ: Magnetic resonance imaging in symptomatic Paget’s disease. Skeletal Radiology 1991, 20:413–418.

    Article  PubMed  CAS  Google Scholar 

  16. Barker DJ, Clough PW, Guyer PB, Gardner MJ: Paget’s disease of bone in 14 British towns. BMJ 1977, 1:1181–1183.

    Article  PubMed  CAS  Google Scholar 

  17. Detheridge FM, Guyer PB, Barker DJ: European distribution of Paget’s disease of bone. BMJ Clinical Research Ed. 1982, 285:1005–1008.

    Article  CAS  Google Scholar 

  18. Detheridge FM, Barker DJ, Guyer PB: Paget’s disease of bone in Ireland. BMJ Clinical Research Ed. 1983, 287:1345–1346.

    Article  CAS  Google Scholar 

  19. Barker DJ: The epidemiology of Paget’s disease of bone. BM Bulletin 1984, 40:396–400.

    CAS  Google Scholar 

  20. Ishikawa Y, Tsukuma H, Miller RW: Low rates of Paget’s disease of bone and osteosarcoma in elderly Japanese. Lancet 1996, 347:1559.

    Article  PubMed  CAS  Google Scholar 

  21. Papapoulos SE: Paget’s disease of bone: clinical, pathogenetic and therapeutic aspects. Baillieres Clin Endocrinol Metab 1997, 11:117–143. A general overview of Paget’s disease with emphasis on newer therapeutic modalities. Clearly written with ample references to the primary sources.

    Article  PubMed  CAS  Google Scholar 

  22. Mills BG, Singer FR: Nuclear inclusions in Paget’s disease of bone. Science 1976, 194:201–202.

    Article  PubMed  CAS  Google Scholar 

  23. Gordon MT, Bell SC, Mee AP, et al.: Prevalence of canine distemper antibodies in the pagetic population. J Med Virol 1993, 40:313–317.

    Article  PubMed  CAS  Google Scholar 

  24. Gordon MT, Mee AP, Anderson DC, Sharpe PT: Canine distemper virus transcripts sequenced from pagetic bone. Bone Mineral 1992, 19:159–174.

    Article  CAS  Google Scholar 

  25. Reddy SV, Singer FR, Mallette L, Roodman GD: Detection of measles virus nucleocapsid transcripts in circulating blood cells from patients with Paget’s disease. J Bone Miner Res 1996, 11:1602–1607.

    Article  PubMed  CAS  Google Scholar 

  26. Cooper C, Dennison E, Kellingray S, et al.: The epidemiology of Paget’s disease in Britain: is the prevalence decreasing? J Bone Min Res 1999 Feb,14(2):192–197. This study reports recent epidemiologic trends in the prevalence of Paget’s disease in England showing a decline in incidence and severity of illness.

    Article  CAS  Google Scholar 

  27. Cundy T, McAnulty K, Wattie D, et al.: Evidence for secular change in Paget’s disease. Bone 1997, 20:69–71. This paper reports recent epidemiologic trends in the prevalence of Paget’s disease. The 5-year prevalence data from 1973–1978 and 1998–1993 from a referral clinic in Auckland, New Zealand are presented. A decline in both incidence and severity (as measured by biochemical and radiographic findings) of Paget’s disease was noted.

    Article  PubMed  CAS  Google Scholar 

  28. Morales-Piga AA, Rey-Rey JS, Corres-Gonzaalez J, et al.:Frequency and characteristics of familial aggregation of Paget’s disease of bone. J Bone Mineral Res 1995, 10:663–670.

    CAS  Google Scholar 

  29. Cody JD, Singer FR, Roodman GD, et al.: Genetic linkage of Paget disease of the bone to chromosome 18q. Am J Hum Genet 1997, 61:1117–1122. One of the first reports of genetic linkage of Paget’s disease to chromosome 18 near the region where the genes for familial expansile osteolysis are located.

    Article  PubMed  CAS  Google Scholar 

  30. 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, 13:911–917. Most recent paper on genetic susceptibility to Paget’s disease. The authors studied the relationship between the 18q21-22 locus and Paget’s disease in eight large multiplex families from diverse ethnic backgrounds with inherited Paget’s disease. Paget’s disease was inherited as an autosomal dominant trait in all families, with high penetrance by the sixth decade.

    Article  PubMed  CAS  Google Scholar 

  31. Wuyts W, Balemans W, Morales-Piga A, et al.: Towards the identification of a second gene locus predisposing to Paget’s disease, Second Joint Meeting of the American Society for Bone and Mineral Research and The International Bone and Mineral Society (Abstract), San Francisco, CA, 1998:S545.

  32. Roodman GD: Osteoclast function in Paget’s disease and multiple myeloma. Bone 1995, 17:57S-61S.

    Article  PubMed  CAS  Google Scholar 

  33. Chappard D, Retailleau-Gaborit N, Filmon R, et al.: Increased nucleolar organizer regions in osteoclast nuclei of Paget’s bone disease. Bone 1998, 22:45–49.

    Article  PubMed  CAS  Google Scholar 

  34. Roodman GD: Advances in bone biology: the osteoclast. Endocrin Rev 1996, 17:308–332. An excellent review of cellular and molecular advances in osteoclast biology, outlining the current state of research.

    CAS  Google Scholar 

  35. Jimi E, Shuto T, Koga T: Macrophage colony-stimulating factor and interleukin-1 alpha maintain the survival of osteoclastlike cells. Endocrinology 1995, 136:808–811.

    Article  PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  37. Roodman GD: Paget’s disease and osteoclast biology. Bone 1996, 19:209–212.

    Article  PubMed  CAS  Google Scholar 

  38. Mee AP, Hoyland JA, Baird P, et al.: Canine bone marrow cell cultures infected with canine distemper virus: an in vitro model of Paget’s disease. Bone 1995, 17:461S-466S.

    Article  PubMed  CAS  Google Scholar 

  39. Roodman GD, Kurihara N, Ohsaki Y, et al.: Interleukin 6: a potential autocrine/paracrine factor in Paget’s disease of bone. J Clin Invest 1992, 89:46–52.

    Article  PubMed  CAS  Google Scholar 

  40. Natale VM, Filho WJ, Duarte AJS: Cellular immunity aspects in elderly subjects with Paget’s disease of bone. Calcif Tissue Int 1997, 60:410–414.

    Article  PubMed  CAS  Google Scholar 

  41. Alam AS, Gallagher A, Shankar V, et al.: Endothelin inhibits osteoclastic bone resorption by a direct effect on cell motility: implications for the vascular control of bone resorption. Endocrinology 1992, 130:3617–3624.

    Article  PubMed  CAS  Google Scholar 

  42. Tarquini R, Perfetto F, Tarquini B: Endothelin-1 and Paget’s bone disease: is there a link? Calcif Tissue Int 1998, 63:118–120.

    Article  PubMed  CAS  Google Scholar 

  43. Choi SJ, Devlin RD, Menaa C, et al.: Cloning and identification of human Sca as a novel inhibitor of osteoclast formation and bone resorption. J Clin Invest 1998, 102:1360–1368. Report of osteoclast inhibitory factor a new class of factors that selectively inhibit osteoclast funtion in vivo.

    Article  PubMed  CAS  Google Scholar 

  44. Delmas PD, Meunier PJ: The management of Paget’s disease of bone. N Engl J Med 1997, 336:558–566. A concise authoritative review of the currently available therapeutic agents for Paget’s disease.

    Article  PubMed  CAS  Google Scholar 

  45. Singer FR, Fredericks RS, Minkin C: Salmon calcitonin therapy for Paget’s disease of bone. The problem of acquired clinical resistance. Arthr Rheum 1980, 23:1148–1154.

    Article  CAS  Google Scholar 

  46. Rodan GA: Mechanisms of action of bisphosphonates. Ann Rev Pharmacol Toxicol 1998, 38:375–388. This paper is a general overview of bisphosphonates and their cellular and molecular modes of action.

    Article  CAS  Google Scholar 

  47. Fleisch H: Bisphosphonates in bone disease: from the laboratory to the patient. New York: Parthenon Publishing Group; 1997.

    Google Scholar 

  48. Papapoulos S: Bisphosphonates: pharmacology and use in the treatment of osteoporosis. In Osteoporsis. Edited by Marcus R, Feldman D, Kelsey J. New York: Academic Press, 1996.

    Google Scholar 

  49. 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, 81:961–967.

    Article  PubMed  CAS  Google Scholar 

  50. Siris ES, Chines AA, Altman RD, et al.: Risedronate in the treatment of Paget’s disease of bone: an open label, multicenter study. J Bone Miner Res 1998, 13:1032–1038.

    Article  PubMed  CAS  Google Scholar 

  51. Singer FR, Clemens TL, Eusebio RA, Bekker PJ: Risedronate, a highly effective oral agent in the treatment of patients with severe Paget’s disease. J Clin Endocrinol Metab 1998, 83:1906–1910.

    Article  PubMed  CAS  Google Scholar 

  52. Fraser WD, Stamp TC, Creek RA, et al.: A double-blind, multicentre, placebo-controlled study of tiludronate in Paget’s disease of bone. Postgrad Med J 1997, 3:496–502.

    Article  Google Scholar 

  53. Coukell AJ, Markham A. Pamidronate: A review of its use in the management of osteolytic bone metastases, tumourinduced hypercalcaemia and Paget’s disease of bone. Drugs Aging 1998, 12:149–168.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Metabolism Section, Department of Medicine, University of California, San Francisco, CA, USA

    Mustafa Noor MD (Postdoctoral fellow)

  2. Department of Veterans, Affairs Medical Center, San Francisco, CA, USA

    Mustafa Noor MD (Postdoctoral fellow)

  3. Department of Veterans Affairs Medical Center, Endocrine Research Unit - 111N, 4150 Clement Street, 94121, San Francisco, CA, USA

    Dolores Shoback MD

  4. Department of Medicine, University of California, San Francisco, CA, USA

    Dolores Shoback MD

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  1. Mustafa Noor MD
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  2. Dolores Shoback MD
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Noor, M., Shoback, D. Paget’s disease of bone: Diagnosis and treatment update. Curr Rheumatol Rep 2, 67–73 (2000). https://doi.org/10.1007/s11926-996-0071-x

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