Advertisement

Paget’s Disease of Bone

  • Dongjie Liu
  • Kenneth W. Lyles
Part of the Contemporary Endocrinology book series (COE, volume 20)

Abstract

Paget’s disease of bone (PDB; osteitis deformans) is a chronic disorder of localized increased bone remodeling, affecting 1.2–3.0% of people over 60 yr of age in the United States. The etiology of PDB is unknown, but current studies suggest that it may be caused by a latent paramyxovirus infection. Families have also been described with a high prevalence of PDB in multiple generations. Eighty percent of these families’ gene for PDB has been localized to the long arm of chromosome 18. PDB can have widely varying clinic manifestations. Symptoms of PDB depend on which part of the skeleton is involved. Bone pain, arthritic symptoms, deformity, neurological compression syndromes, fracture, and, rarely, malignant degeneration can occur in affected patients. When the diagnosis of PDB is considered, the patient should have a radioisotopic total body bone scan to localize areas of increased disease activity, then areas of increased tracer uptake should be radiographed to confirm the diagnosis. Serum markers of bone formation, such as alkaline phosphotase and bone-specific alkaline phosphotase, can be used to diagnose the disease, as well as monitor response to therapy. Urinary excretion of skeletal breakdown products (hydroxyproline, pyridinoline, N-telopeptides) are markers of bone resorption.

Keywords

Giant Cell Tumor Canine Distemper Virus Robertsonian Translocation Serum Alkaline Phosphatase Level Angioid Streak 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Paget J. On a form of chronic inflammation of bone (osteitis deformans). Trans Med Chir Soc 1977; 60:37–63.Google Scholar
  2. 2.
    Kaplan FS, Singer FR. Paget’s disease of bone: pathophysiology diagnosis and management. J Am Acad Orthoped Surg 1995;3:336–344.Google Scholar
  3. 3.
    Siris ES. Management of Paget’s disease of bone in the era of new and more potent bisphosdhonates. Endocr Prac 1997;3:264–266.Google Scholar
  4. 4.
    Morales Piga A, Lopez-Abente G, Garcia Vadillo A, Ibanez AE, Gonzales-Lanza M. Features of Paget’s disease of bone in a new high-prevalence focus. Med Clin 1990;95:169–174.Google Scholar
  5. 5.
    Kanis JA. Pathophysiology and Treatment of Paget’s Disease of Bone. Carolina, London, 1991.Google Scholar
  6. 6.
    Galbraith HJB, Evans E, Lacey J. Paget’s disease of bone. A clinical and genetic study. Postgrad Med J 1977;53:33–39.PubMedCrossRefGoogle Scholar
  7. 7.
    Whyte MP, Daniels EH, Murphy WA. Osteolytic Paget’s bone disease in a young man. Am J Med 1985; 78:326–332.PubMedCrossRefGoogle Scholar
  8. 8.
    Merkow RL, Lane JM. Paget’s disease of bone. Orthop Clin N Am 1990;21:171–189.Google Scholar
  9. 9.
    Barker DJP, ed. The epidemiology of Paget’s disease. In: Barker DJP, ed. Proceedings of MRC Sym-posium on Paget’s Disease (Scientific Reports No. 5), Medical Research Council, Southhampton, UK, 1983, pp. 1–6.Google Scholar
  10. 10.
    Morales-Piga AA, Rey-Rey JS, Corres-Gonzalez J, et al. Frequency and characteristics of familial aggregation of Paget’s disease of bone. J Bone Miner Res 1995;10:663–670.PubMedCrossRefGoogle Scholar
  11. 11.
    Cundy T. Evidence for a secular change in Paget’s disease. Bone 1997;20:69–71.PubMedCrossRefGoogle Scholar
  12. 12.
    Soafer JA. Evidence for periodicity in incidence of Paget’s disease. In: Barker DJP, ed. Proceedings of MRC Symposium on Paget’s Disease (Scientific Reports No. 5), Medical Research Council, South-hampton, UK, 1983, pp. 16–21.Google Scholar
  13. 13.
    Siris ES, Ottman R, Flaster E, Kelsey JL. Familial aggregation of Paget’ s disease of bone. J Bone Miner Res 1991;6:495–500.PubMedCrossRefGoogle Scholar
  14. 14.
    Fraser WD. Paget’s disease of bone. Curr Opin Rheumatol 1997;9:347–354.PubMedCrossRefGoogle Scholar
  15. 15.
    Barker DJP. The epidemiology of Paget’s disease of bone. B Med Bull 1984;40:396–400.Google Scholar
  16. 16.
    Kim GS, et al. Paget bone disease involving young adults in 3 generations of a Korean family. Medicine 1997;76:157–169.PubMedCrossRefGoogle Scholar
  17. 17.
    Evens RG, Bartter FC. The hereditery aspects of Paget’s disease. JAMA 1985;205:900–902.CrossRefGoogle Scholar
  18. 18.
    Singer FR, Mills BG, Park MS, Takemura S, Terasaki PI. Increased HLA-DRW1 antigen frequency in Paget’s disease of bone. Clin Res 1985;33:547A.Google Scholar
  19. 19.
    Godon MT, Carwright EJ, Mercer S, Anderson DC, Sharpe PT. HLA polymorphism in Paget’s disease of bone. Semin Arthritis Rheum 1994;23:229.CrossRefGoogle Scholar
  20. 20.
    Leach RJ, et al. Evidence of a locus for Paget’s disease of bone on human chromosome 18Q. J Bone Mineral Res 1996;11(Suppl 1):S99,S108.Google Scholar
  21. 21.
    Hansen MF, et al. Co-localization on chromosome 18 of a novel osteosarcoma supressor gene with a predisposition for Paget’s disease of bone. J Bone Miner Res 1997;12(Suppl 1):S108.Google Scholar
  22. 22.
    Hughes AE, Shearman AM, Weber JL, et al. Genetic linkage of familial expansile osteolysis to chromo-some 18q. Hum Mol Genet 1994;3:359–361.PubMedCrossRefGoogle Scholar
  23. 23.
    Tilyard MW, Gardner RJM, Milligan L, et al. A probable linkage between familial Paget’s disease and HLA loci. Aust N Z J Med 1982;12:498–450.PubMedCrossRefGoogle Scholar
  24. 24.
    Mils BG, Oizumi J, Kudo E, Rude R. Robertsonian translocation in Paget’s disease of bone. J Orthop Res 1997;15:477–481.CrossRefGoogle Scholar
  25. 25.
    Kaplan FS, Singer FR. Paget’ s disease of bone: pathophysiology and diagnosis. Instr Course Lect 1993; 42:417–424.PubMedGoogle Scholar
  26. 26.
    Detheridge FM, Guyer PB, Abarker DJP. European distribution of Paget’s disease of bone. Br Med J 1982;285:1005–1008.CrossRefGoogle Scholar
  27. 27.
    Hamdy RC. Paget’s disease of the bone. Clin Geriatr Med 1994;10:719–735.PubMedGoogle Scholar
  28. 28.
    Barker DJP, Chamberlain AT, Guyer AB, et al. Paget’s disease of bone: the Lancashire focus. Br Med J 1980;280:1105–1107.PubMedCrossRefGoogle Scholar
  29. 29.
    Piga AM, Lopez-Abente G, Ibanez AE, et al. Risk factors for Paget’s disease: a new hypothesis. Int J Epidemiol 1988;17:198–201.PubMedCrossRefGoogle Scholar
  30. 30.
    Reddy SV, et al. Detection of measles virus nucleocapsid transcripts in circulating blood cells from patients with Paget’s disease. J Bone Miner Res 1997;11:1602–1607.CrossRefGoogle Scholar
  31. 31.
    Rebel A, Malkani K, Basle J. Anomalies nucleaires des osteoclasts de la maladie osseuse de Paget. Nouv Presse Med 1974;3:1299–1301.PubMedGoogle Scholar
  32. 32.
    Mills BG, Frausto A, Singer RF, et al. Multinucleated cells formed in vitro from Paget’s bone marrow express viral antigens. Bone 1994; 15:443–448.PubMedCrossRefGoogle Scholar
  33. 33.
    Kahn AJ. The viral etiology of Paget’s diseases of bone: a perspective. Calc Tissue Int 1990;47: 127–129.CrossRefGoogle Scholar
  34. 34.
    Mee AP, May C, Bennett D, Sharpe PT. Generation of multinucleated osteoclast-like cells from canine bone marrow: effects of canine distemper virus. Bone 1995;17:47–55.PubMedCrossRefGoogle Scholar
  35. 35.
    Mee AP, Hoyland JA, Baird P, Bennett D, Sharpe PT. Canine bone marrow cell cultures infected with canine distemper virus: an in vitro model of Paget’s disease. Bone 1995;17(Suppl 4):461s-466s.PubMedCrossRefGoogle Scholar
  36. 36.
    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.PubMedCrossRefGoogle Scholar
  37. 37.
    Ralston SH, Digiovine FS, Gallacher SJ, et al. Failure to detect paramyxovirus sequenses in Paget’s disease of bone using the polyperase chain reaction. J Bone Miner Res 1991;6:1243–1248.PubMedCrossRefGoogle Scholar
  38. 38.
    Birch MA, Taylorm W, Fraser WD, et al. Absence of paramyxovirus RNA in cultures of Paget’ s bone cells and in Paget’s bone. J Bone Miner Res 1994;9:11–16.PubMedCrossRefGoogle Scholar
  39. 39.
    Mills BG, Singer FR. Critical evaluation of viral antigen data in Paget’s disease of bone. Clin Orthop 1987;217:16–25.PubMedGoogle Scholar
  40. 40.
    Ruddle NH, Paul N, Horowitz M, et al. HTLV-1 activation of lyphotoxic (TNF-beta) production and high-turnover in bone disease. Calcif Tissue Int 1990;46:A58.Google Scholar
  41. 41.
    Hoyland JA, Freemont AJ, Sharp PT. Interleukin-6, IL-6 receptor, and IL-6 nuclear factor gene expres-sion in Paget’s disease. J Bone Miner Res 1994;9:75–80.PubMedCrossRefGoogle Scholar
  42. 42.
    Hoyland JA, Sharp PT. Upregulation of c-Fos proto-oncogene expression in Paget’ s osteoclasts. J Bone Miner Res 1994;8:1191–1194.Google Scholar
  43. 43.
    Ralston SH, Hoey SA, Gallacher SJ, et al. Cytokine and growth factor expression in Paget’s disease: analysis by reverse transcriptase/polyperase chain reaction. Br J Rheumatol 1994;33:620–625.PubMedCrossRefGoogle Scholar
  44. 44.
    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.PubMedCrossRefGoogle Scholar
  45. 45.
    Birch AM, Ginty AF, Walsh CA, et al. PCR detection of cytokines in normal human and pagetic osteoblast-like cells. J Bone Miner Res 1993;8:1155–1162.PubMedCrossRefGoogle Scholar
  46. 46.
    Ooi CG, Fraser WD. Paget’s disease of bone. Postgrad Med J 1997;73:69–74.PubMedCrossRefGoogle Scholar
  47. 47.
    Hosking D, Meunier PJ, Ringe JD, et al. Paget’s disease of bone: diagnosis and management. Br Med J 1996;312:491–494.CrossRefGoogle Scholar
  48. 48.
    Menwier PJ, Salson C, Mathieu L, et al. Skeletal distribution and biochemical parameters of Paget’s disease. Clin Orthop 1987;217:37–44.Google Scholar
  49. 49.
    Hadijipavlou A, Lander P. Paget’s disease of the spine. J Bone Joint Surg Am 1991;73:1376–1381.Google Scholar
  50. 50.
    Ikeda K, Kinoshita M, Aiki, K, Tomatsuri A. Hydrocephalic parkinsonism due to Paget’s disease of bone: dramatic improvement following ventriculoperitoneal shunt and temporary levodopa/carbidopa therapy. Movement Dis 1997;12:241–242.PubMedCrossRefGoogle Scholar
  51. 51.
    Smith BJ, Everson JW. Paget’ s disease of bone with particular reference to dentistry. J Oral Pathol 1981; 10:233–247.PubMedCrossRefGoogle Scholar
  52. 52.
    Havos AG, Butler A, Bretsky SS. Osteogenic sarcoma associated with Paget’s disease of bone: a clinicopathologic study of 65 patients. Cancer 1983;52:1489–1495.CrossRefGoogle Scholar
  53. 53.
    Bhambhani M, Lamberty BG, Clements MR, et al. Giant cell tumor in mandible and spine: a rare complication of Paget’s disease of bone. Ann Rheum Dis 1992;51:1335–1337.PubMedCrossRefGoogle Scholar
  54. 54.
    Singer FE, Mills BG. Giant cell tumor arising in Paget’s disease of bone. Recurrences after 36 years. Clin Orth Rel Res 1993;293:293–301.Google Scholar
  55. 55.
    Harinck HIJ, Biwoet OLM, Vellenga CJLR, et al. Relation between signs and symptoms in Paget’s disease. Q J Med 1986;226:133–151.Google Scholar
  56. 56.
    Crisp AJ. Paget’s disease of bone. In: Maddison PJ, et al., eds. Oxford Textbook of Rheumatology. Oxford University, Oxford, 1993, pp. 1025–1031.Google Scholar
  57. 57.
    Morales-Pila M, Rey-Rey JS, Corres-Gonzalee J, et al. Frequency and characteristics of familial aggre-gation of Paget’s disease of bone. J Bone Miner Res 1995;10:663–670.CrossRefGoogle Scholar
  58. 58.
    Lyles KW, Gold DT, Newton RA, et al. Peyronies disease is associated with Paget’s disease of bone. J Bone Miner Res 1997;12:929–934.PubMedCrossRefGoogle Scholar
  59. 59.
    Gass JDM, Clarkson JG. Angioid streaks and disciform macular detachment in Paget’ s disease (osteitis deformans). Am J Opthal 1973;75:576–586.Google Scholar
  60. 60.
    Babb TR, Skvoat K. Prevalence of angioid streaks and other ocular complications of Paget’s disease of bone. Br J Opthal 1990;74:579–582.CrossRefGoogle Scholar
  61. 61.
    Mirra JM, Brien EW, Tehranzaoah J. Paget’s disease of bone review with emphasis on radiologic features: part I and part II. Skeletal Radiol 1995;24:163–171 and 173–184.PubMedGoogle Scholar
  62. 62.
    Kanis JA. Pathophysiology and Treatment of Paget’s Disease of Bone. Carolina Academic, Durham, NC, 1991, pp. 1–15.Google Scholar
  63. 63.
    Lyles KW, Lammers JE, Shipp KM, et al. Functional and mobility impairments associated with Paget’ s disease of bone. J Am Geriatr Soc 1995;43:502–506.PubMedGoogle Scholar
  64. 64.
    Delmas BD, Meunier PJ. The management of Paget’s disease of bone. N Engl J Med 1997;336:558–566.PubMedCrossRefGoogle Scholar
  65. 65.
    Siris ES, Weinstein RS, Altman RD, 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.PubMedCrossRefGoogle Scholar
  66. 66.
    O’Doherty DP, McCloskey EV, Eyes KS, et al. The effects of intravenous alendronate in Paget’ s disease of bone. J Bone Miner Res 1995;10:1094–1100.PubMedCrossRefGoogle Scholar
  67. 67.
    Fleish H. Bisphosphanates in Bone Disease, 3rd ed. Parthenon, New York, 1997, pp. 69–83.Google Scholar
  68. 68.
    Siris ES. Management of Paget’s disease of bone in the era of new and more potent bisphosphonates. Endocr Prac 1997;3:264–266.Google Scholar
  69. 69.
    Hosking DJ, Eusebro RA, Chingz AA. Paget’s disease of bone: reduction of disease activity with oral risedronate. Bone 1998;22:51–55.PubMedCrossRefGoogle Scholar
  70. 70.
    Bockman RS, Weinerman SA. Medical treatment for Paget’s disease of bone. Instr. Course Lect 1993; 42:425–433.PubMedGoogle Scholar
  71. 71.
    Ludkowski P, Wilson-MacDonald J. Total arthroplasty in Paget’s disease of the hip: a clinical review and review of the literature. Clin Orthop 1990;255:160–167.PubMedGoogle Scholar
  72. 72.
    Meyers MH, Singer FR. Osteotomy for tibia virus in Paget’s disease under cover of calcitonin. J Bone Joint Surg Am 1978;60:810–814.PubMedGoogle Scholar
  73. 73.
    Lovette EL, Lammens T, Rabry G. The ilizarov external fixator for treatment of deformities in Paget’s disease. Clin Orthop Related Res 1996;323:298–303.CrossRefGoogle Scholar
  74. 74.
    Hughes AD, Shearman AM, Weber JL, et al. Genetic linkage of familial expansile osteolysis to chromo-some 18q. Hum Mol Genet 1995;3:359–361.CrossRefGoogle Scholar

Copyright information

© Humana Press Inc., Totowa, NJ 2000

Authors and Affiliations

  • Dongjie Liu
  • Kenneth W. Lyles

There are no affiliations available

Personalised recommendations