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Paget’s Disease of Bone: Pathogenesis and Treatment

  • Frederick R. Singer
  • G. David Roodman
Chapter
Part of the Topics in Bone Biology book series (TBB, volume 7)

Abstract

Paget’s disease of bone (PDB) is a skeletal disorder that usually is diagnosed in patients over 50 years of age and affects one or several bones but not the entire skeleton. Radiological and pathological studies indicate that the underlying problem is an increase in osteoclastic activity, which initially produces dominant osteolytic lesions that move slowly throughout an affected bone. Over time, the osteolytic areas are replaced by osteosclerotic bone of increased size and chaotic structure. In the lower extremities, affected bones may become bowed due to impaired biomechanical properties of the bone. The overgrowth of bone is produced by a marked proliferation of osteoblasts.

Keywords

Paget’s disease of bone Measles virus Paramyxovirus Nucleocapsid Osteolytic lesions Bone remodeling 

References

  1. 1.
    Abe S, Ohno T, Park P, Higaki S, Unno K, Tateishi A. Viral behavior of paracrystalline inclusions in osteoclasts of Paget’s disease of bone. Ultrastruct Pathol. 1995;19:455–61.PubMedGoogle Scholar
  2. 2.
    Albagha OM, Visconti MR, Alonso N, Langston AL, Cundy T, Dargie R, Dunlop MG, Fraser WD, Hooper MJ, Isaia G, Nicholson GC, del Pino MJ, Gonzalez-Sarmiento R, di Stefano M, Tenesa A, Walsh JP, Ralston SH. Genome-wide association study identifies variants at CSF1, OPTN and TNFRSF11A as genetic risk factors for Paget’s disease of bone. Nat Genet. 2010;42:520–4.PubMedGoogle Scholar
  3. 3.
    Badadani M, Nalbandian A, Watts GD, Vesa J, Kitazawa M, Su H, Tanaja J, Dec E, Wallace DC, Mukherjee J, Caiozzo V, Warman M, Kimonis VE. VCP associated inclusion body myopathy and paget disease of bone knock-in mouse model exhibits tissue pathology typical of human disease. PLoS One. 2010;;5.Google Scholar
  4. 4.
    Basle M, Rebel A, Pouplard A, Kouyoumdjian S, Filmon R, Lepatezour A. Demonstration of measles virus antigens in osteoclasts in Paget’s disease of bone. C R Seances Acad Sci D. 1979;289:225–8.PubMedGoogle Scholar
  5. 5.
    Basle MF, Fournier JG, Rozenblatt S, Rebel A, Bouteille M. Measles virus RNA detected in Paget’s disease bone tissue by in situ hybridization. J Gen Virol. 1986;67(Pt 5):907–13.PubMedGoogle Scholar
  6. 6.
    Bastin S, Bird H, Gamble G, Cundy T. Paget’s disease of bone – becoming a rarity? Rheumatology (Oxford). 2009;48:1232–5.Google Scholar
  7. 7.
    Beclere M. Radiographie d’un cas de maladie de Paget. Bull Mem Soc Med Hop Paris. 1901;18:929–31.Google Scholar
  8. 8.
    Beneton MN, Harris S, Kanis JA. Paramyxovirus-like inclusions in two cases of pycnodysostosis. Bone. 1987;8:211–7.PubMedGoogle Scholar
  9. 9.
    Bertoldo F, Pancheri S, Zenari S, Boldini S, Giovanazzi B, Zanatta M, Valenti MT, Dalle Carbonare L, Lo Cascio V. Serum 25-hydroxyvitamin D levels modulate the acute-phase response associated with the first nitrogen-containing bisphosphonate infusion. J Bone Miner Res. 2010;25:447–54.PubMedGoogle Scholar
  10. 10.
    Beyens G, Daroszewska A, de Freitas F, Fransen E, Vanhoenacker F, Verbruggen L, Zmierczak HG, Westhovens R, Van Offel J, Ralston SH, Devogelaer JP, Van Hul W. Identification of sex-specific associations between polymorphisms of the osteoprotegerin gene, TNFRSF11B, and Paget’s disease of bone. J Bone Miner Res. 2007;22:1062–71.PubMedGoogle Scholar
  11. 11.
    Bianco P, Silvestrini G, Ballanti P, Bonucci E. Paramyxovirus-like nuclear inclusions identical to those of Paget’s disease of bone detected in giant cells of primary oxalosis. Virchows Arch A Pathol Anat Histopathol. 1992;421:427–33.PubMedGoogle Scholar
  12. 12.
    Birch MA, Taylor W, Fraser WD, Ralston SH, Hart CA, Gallagher JA. Absence of paramyxovirus RNA in cultures of pagetic bone cells and in pagetic bone. J Bone Miner Res. 1994;9:11–6.PubMedGoogle Scholar
  13. 13.
    Brailsford JF. Paget’s disease of bone, its frequency, diagnosis, and complications. Br J Radiol. 1938;128:507.Google Scholar
  14. 14.
    Cartwright EJ, Gordon MT, Freemont AJ, Anderson DC, Sharpe PT. Paramyxoviruses and Paget’s disease. J Med Virol. 1993;40:133–41.PubMedGoogle Scholar
  15. 15.
    Chung PY, Beyens G, Boonen S, Papapoulos S, Geusens P, Karperien M, Vanhoenacker F, Verbruggen L, Fransen E, Van Offel J, Goemaere S, Zmierczak HG, Westhovens R, Devogelaer JP, Van Hul W. The majority of the genetic risk for Paget’s disease of bone is explained by genetic variants close to the CSF1, OPTN, TM7SF4, and TNFRSF11A genes. Hum Genet. 2010;128:615–26.PubMedGoogle Scholar
  16. 16.
    Chung PY, Beyens G, Guanabens N, Boonen S, Papapoulos S, Karperien M, Eekhoff M, Van Wesenbeeck L, Jennes K, Geusens P, Offeciers E, Van Offel J, Westhovens R, Zmierczak H, Devogelaer JP, Van Hul W. Founder effect in different European countries for the recurrent P392L SQSTM1 mutation in Paget’s disease of bone. Calcif Tissue Int. 2008;83:34–42.PubMedGoogle Scholar
  17. 17.
    Chung PY, Beyens G, Riches PL, Van Wesenbeeck L, de Freitas F, Jennes K, Daroszewska A, Fransen E, Boonen S, Geusens P, Vanhoenacker F, Verbruggen L, Van Offel J, Goemaere S, Zmierczak HG, Westhovens R, Karperien M, Papapoulos S, Ralston SH, Devogelaer JP, Van Hul W. Genetic variation in the TNFRSF11A gene encoding RANK is associated with susceptibility to Paget’s disease of bone. J Bone Miner Res. 2010;25:2316–29.Google Scholar
  18. 18.
    Collet C, Michou L, Audran M, Chasseigneaux S, Hilliquin P, Bardin T, Lemaire I, Cornelis F, Launay JM, Orcel P, Laplanche JL. Paget’s disease of bone in the French population: novel SQSTM1 mutations, functional analysis, and genotype-phenotype correlations. J Bone Miner Res. 2007;22:310–7.PubMedGoogle Scholar
  19. 19.
    Cundy T, Wattie D, King AR. High-dose pamidronate in the management of resistant Paget’s disease. Calcif Tissue Int. 1996;58:6–8.PubMedGoogle Scholar
  20. 20.
    Custer SK, Neumann M, Lu H, Wright AC, Taylor JP. Transgenic mice expressing mutant forms VCP/p97 recapitulate the full spectrum of IBMPFD including degeneration in muscle, brain and bone. Hum Mol Genet. 2010;19:1741–55.PubMedGoogle Scholar
  21. 21.
    Daroszewska A, Hocking LJ, McGuigan FE, Langdahl B, Stone MD, Cundy T, Nicholson GC, Fraser WD, Ralston SH. Susceptibility to Paget’s disease of bone is influenced by a common polymorphic variant of osteoprotegerin. J Bone Miner Res. 2004;19:1506–11.PubMedGoogle Scholar
  22. 22.
    Dickson GR, Shirodria PV, Kanis JA, Beneton MN, Carr KE, Mollan RA. Familial expansile osteolysis: a morphological, histomorphometric and serological study. Bone. 1991;12:331–8.PubMedGoogle Scholar
  23. 23.
    Edholm OG, Howarth S. Studies on the peripheral circulation in osteitis deformans. Clin Sci (Lond). 1953;12:277–91.Google Scholar
  24. 24.
    Eekhoff ME, van der Klift M, Kroon HM, Cooper C, Hofman A, Pols HA, Papapoulos SE. Paget’s Disease of bone in the Netherlands: a population-based radiological and biochemical survey – the Rotterdam study. J Bone Miner Res. 2004;19:566–70.PubMedGoogle Scholar
  25. 25.
    el Sammaa M, Linthicum Jr FH, House HP, House JW. Calcitonin as treatment for hearing loss in Paget’s disease. Am J Otol. 1986;7:241–3.PubMedGoogle Scholar
  26. 26.
    Erdheim J. Ueber die genese der Paget’schen knochenerkrankung. Beitr z path Anat u z allg Path. 1935;96:1–60.Google Scholar
  27. 27.
    Forman MS, Mackenzie IR, Cairns NJ, Swanson E, Boyer PJ, Drachman DA, Jhaveri BS, Karlawish JH, Pestronk A, Smith TW, Tu PH, Watts GD, Markesbery WR, Smith CD, Kimonis VE. Novel ubiquitin neuropathology in frontotemporal dementia with valosin-containing protein gene mutations. J Neuropathol Exp Neurol. 2006;65:571–81.PubMedGoogle Scholar
  28. 28.
    Franck WA, Bress NM, Singer FR, Krane SM. Rheumatic manifestations of Paget’s disease of bone. Am J Med. 1974;56:592–603.PubMedGoogle Scholar
  29. 29.
    Gabel GT, Rand JA, Sim FH. Total knee arthroplasty for osteoarthrosis in patients who have Paget disease of bone at the knee. J Bone Joint Surg Am. 1991;73:739–44.PubMedGoogle Scholar
  30. 30.
    Gennari L, Gianfrancesco F, Di Stefano M, Rendina D, Merlotti D, Esposito T, Gallone S, Fusco P, Rainero I, Fenoglio P, Mancini M, Martini G, Bergui S, De Filippo G, Isaia G, Strazzullo P, Nuti R, Mossetti G. SQSTM1 gene analysis and gene-environment interaction in Paget’s disease of bone. J Bone Miner Res. 2010;25:1375–84.PubMedGoogle Scholar
  31. 31.
    Gibbs CJ, Aaron JE, Peacock M. Osteomalacia in Paget’s disease treated with short term, high dose sodium etidronate. Br Med J (Clin Res Ed). 1986;292:1227–9.Google Scholar
  32. 32.
    Goode A, Layfield R. Recent advances in understanding the molecular basis of Paget disease of bone. J Clin Pathol. 2010;63:199–203.PubMedGoogle Scholar
  33. 33.
    Gordon MT, Anderson DC, Sharpe PT. Canine distemper virus localised in bone cells of patients with Paget’s disease. Bone. 1991;12:195–201.PubMedGoogle Scholar
  34. 34.
    Gordon MT, Mee AP, Anderson DC, Sharpe PT. Canine distemper virus transcripts sequenced from pagetic bone. Bone Miner. 1992;19:159–74.PubMedGoogle Scholar
  35. 35.
    Gutteridge DH, Ward LC, Stewart GO, Retallack RW, Will RK, Prince RL, Criddle A, Bhagat CI, Stuckey BG, Price RI, Kent GN, Faulkner DL, Geelhoed E, Gan SK, Vasikaran S. Paget’s disease: acquired resistance to one aminobisphosphonate with retained response to another. J Bone Miner Res. 1999;14 Suppl 2:79–84.PubMedGoogle Scholar
  36. 36.
    Hamadouche M, Mathieu M, Topouchian V, de Pinieux G, Courpied JP. Transfer of Paget’s disease from one part of the skeleton to another as a result of autogenous bone-grafting: a case report. J Bone Joint Surg Am. 2002;84-A:2056–61.PubMedGoogle Scholar
  37. 37.
    Haworth S. Cardiac output in osteitis deformans. Clin Sci. 1953;12:271–5.Google Scholar
  38. 38.
    Helfrich MH, Hobson RP, Grabowski PS, Zurbriggen A, Cosby SL, Dickson GR, Fraser WD, Ooi CG, Selby PL, Crisp AJ, Wallace RG, Kahn S, Ralston SH. A negative search for a paramyxoviral etiology of Paget’s disease of bone: molecular, immunological, and ultrastructural studies in UK patients. J Bone Miner Res. 2000;15:2315–29.PubMedGoogle Scholar
  39. 39.
    Hiruma Y, Kurihara N, Subler MA, Zhou H, Boykin CS, Zhang H, Ishizuka S, Dempster DW, Roodman GD, Windle JJ. A SQSTM1/p62 mutation linked to Paget’s disease increases the osteoclastogenic potential of the bone microenvironment. Hum Mol Genet. 2008;17:3708–19.PubMedGoogle Scholar
  40. 40.
    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. Long-term control of bone turnover in Paget’s disease with zoledronic acid and risedronate. J Bone Miner Res. 2007;22:142–8.PubMedGoogle Scholar
  41. 41.
    Howatson AF, Fornasier VL. Microfilaments associated with Paget’s disease of bone: comparison with nucleocapsids of measles virus and respiratory syncytial virus. Intervirology. 1982;18:150–9.PubMedGoogle Scholar
  42. 42.
    Hoyland JA, Dixon JA, Berry JL, Davies M, Selby PL, Mee AP. A comparison of in situ hybridisation, reverse transcriptase-polymerase chain reaction (RT-PCR) and in situ-RT-PCR for the detection of canine distemper virus RNA in Paget’s disease. J Virol Methods. 2003;109:253–9.PubMedGoogle Scholar
  43. 43.
    Hubbers CU, Clemen CS, Kesper K, Boddrich A, Hofmann A, Kamarainen O, Tolksdorf K, Stumpf M, Reichelt J, Roth U, Krause S, Watts G, Kimonis V, Wattjes MP, Reimann J, Thal DR, Biermann K, Evert BO, Lochmuller H, Wanker EE, Schoser BG, Noegel AA, Schroder R. Pathological consequences of VCP mutations on human striated muscle. Brain. 2007;130:381–93.PubMedGoogle Scholar
  44. 44.
    Ju JS, Weihl CC. Inclusion body myopathy, Paget’s disease of the bone and fronto-temporal dementia: a disorder of autophagy. Hum Mol Genet. 2010;19:R38–45.PubMedGoogle Scholar
  45. 45.
    Khairi MR, Altman RD, DeRosa GP, Zimmermann J, Schenk RK, Johnston CC. Sodium etidronate in the treatment of Paget’s disease of bone. A study of long-term results. Ann Intern Med. 1977;87:656–63.PubMedGoogle Scholar
  46. 46.
    Khan SA, Brennan P, Newman J, Gray RE, McCloskey EV, Kanis JA. Paget’s disease of bone and unvaccinated dogs. Bone. 1996;19:47–50.PubMedGoogle Scholar
  47. 47.
    Khurjekar KS, Vidyadhara S, Dheenadhayalan J, Rajasekaran S. Spontaneous rapid osteolysis in Paget’s disease after internal fixation of subtrochanteric femoral fracture. Singapore Med J. 2006;47:897–900.PubMedGoogle Scholar
  48. 48.
    Kimonis VE, Mehta SG, Fulchiero EC, Thomasova D, Pasquali M, Boycott K, Neilan EG, Kartashov A, Forman MS, Tucker S, Kimonis K, Mumm S, Whyte MP, Smith CD, Watts GD. Clinical studies in familial VCP myopathy associated with Paget disease of bone and frontotemporal dementia. Am J Med Genet A. 2008;146A:745–57.PubMedGoogle Scholar
  49. 49.
    Kukita A, Chenu C, McManus LM, Mundy GR, Roodman GD. Atypical multinucleated cells form in long-term marrow cultures from patients with Paget’s disease. J Clin Invest. 1990;85:1280–6.PubMedGoogle Scholar
  50. 50.
    Kumar KR, Needham M, Mina K, Davis M, Brewer J, Staples C, Ng K, Sue CM, Mastaglia FL. Two Australian families with inclusion-body myopathy, Paget’s disease of bone and frontotemporal dementia: novel clinical and genetic findings. Neuromuscul Disord. 2010;20:330–4.PubMedGoogle Scholar
  51. 51.
    Kurihara N, Hiruma Y, Yamana K, Michou L, Rousseau C, Morissette J, Galson DL, Teramachi J, Zhou H, Dempster DW, Windle JJ, Brown JP, Roodman GD. Contributions of the measles virus nucleocapsid gene and the SQSTM1/p62P392L mutation to Paget’s disease. Cell Metab. 2011;13:23–34.PubMedGoogle Scholar
  52. 52.
    Kurihara N, Hiruma Y, Zhou H, Subler MA, Dempster DW, Singer FR, Reddy SV, Gruber HE, Windle JJ, Roodman GD. Mutation of the sequestosome 1 (p62) gene increases osteoclastogenesis but does not induce Paget disease. J Clin Invest. 2007;117:133–42.PubMedGoogle Scholar
  53. 53.
    Kurihara N, Reddy SV, Araki N, Ishizuka S, Ozono K, Cornish J, Cundy T, Singer FR, Roodman GD. Role of TAFII-17, a VDR binding protein, in the increased osteoclast formation in Paget’s disease. J Bone Miner Res. 2004;19:1154–64.PubMedGoogle Scholar
  54. 54.
    Kurihara N, Reddy SV, Menaa C, Anderson D, Roodman GD. Osteoclasts expressing the measles virus nucleocapsid gene display a pagetic phenotype. J Clin Invest. 2000;105:607–14.PubMedGoogle Scholar
  55. 55.
    Kurihara N, Zhou H, Reddy SV, Garcia Palacios V, Subler MA, Dempster DW, Windle JJ, Roodman GD. Expression of measles virus nucleocapsid protein in osteoclasts induces Paget’s disease-like bone lesions in mice. J Bone Miner Res. 2006;21:446–55.PubMedGoogle Scholar
  56. 56.
    Laurin N, Brown JP, Morissette J, Raymond V. Recurrent mutation of the gene encoding sequestosome 1 (SQSTM1/p62) in Paget disease of bone. Am J Hum Genet. 2002;70:1582–8.PubMedGoogle Scholar
  57. 57.
    Leopold-Levi M, Londe A. Application des rayons de Roentgen a l’etude de la texture. N iconog de la Salpetriere. 1897;X:198–201.Google Scholar
  58. 58.
    Lucas GJ, Hocking LJ, Daroszewska A, Cundy T, Nicholson GC, Walsh JP, Fraser WD, Meier C, Hooper MJ, Ralston SH. Ubiquitin-associated domain mutations of SQSTM1 in Paget’s disease of bone: evidence for a founder effect in patients of British descent. J Bone Miner Res. 2005;20:227–31.PubMedGoogle Scholar
  59. 59.
    Lucas GJ, Mehta SG, Hocking LJ, Stewart TL, Cundy T, Nicholson GC, Walsh JP, Fraser WD, Watts GD, Ralston SH, Kimonis VE. Evaluation of the role of valosin-containing protein in the pathogenesis of familial and sporadic Paget’s disease of bone. Bone. 2006;38:280–5.PubMedGoogle Scholar
  60. 60.
    Lusty PJ, Walter WL, Walter WK, Zicat B. Cementless hip arthroplasty in Paget’s disease at medium-term follow-up (average of 6.7 years). J Arthroplasty. 2007;22:692–6.PubMedGoogle Scholar
  61. 61.
    Mackenzie I, Young C, Fraser WD. Tinnitus and Paget’s disease of bone. J Laryngol Otol. 2006;120:899–902.PubMedGoogle Scholar
  62. 62.
    Maldague B, Malghem J. Dynamic radiologic patterns of Paget’s disease of bone. Clin Orthop Relat Res. 1987;217:126–51.PubMedGoogle Scholar
  63. 63.
    Mangham DC, Davie MW, Grimer RJ. Sarcoma arising in Paget’s disease of bone: declining incidence and increasing age at presentation. Bone. 2009;44:431–6.PubMedGoogle Scholar
  64. 64.
    Marr DS, Rosenthal DI, Cohen GL, Tomford WW. Rapid postoperative osteolysis in Paget disease. A case report. J Bone Joint Surg Am. 1994;76:274–7.PubMedGoogle Scholar
  65. 65.
    Matthews BG, Afzal MA, Minor PD, Bava U, Callon KE, Pitto RP, Cundy T, Cornish J, Reid IR, Naot D. Failure to detect measles virus ribonucleic acid in bone cells from patients with Paget’s disease. J Clin Endocrinol Metab. 2008;93:1398–401.PubMedGoogle Scholar
  66. 66.
    McDonald DJ, Sim FH. Total hip arthroplasty in Paget’s disease. A follow-up note. J Bone Joint Surg Am. 1987;69:766–72.PubMedGoogle Scholar
  67. 67.
    Mee AP, Dixon JA, Hoyland JA, Davies M, Selby PL, Mawer EB. Detection of canine distemper virus in 100% of Paget’s disease samples by in situ-reverse transcriptase-polymerase chain reaction. Bone. 1998;23:171–5.PubMedGoogle Scholar
  68. 68.
    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;17:461S–6.PubMedGoogle Scholar
  69. 69.
    Menaa C, Reddy SV, Kurihara N, Maeda H, Anderson D, Cundy T, Cornish J, Singer FR, Bruder JM, Roodman GD. Enhanced RANK ligand expression and responsivity of bone marrow cells in Paget’s disease of bone. J Clin Invest. 2000;105:1833–8.PubMedGoogle Scholar
  70. 70.
    Merchant A, Smielewska M, Patel N, Akunowicz JD, Saria EA, Delaney JD, Leach RJ, Seton M, Hansen MF. Somatic mutations in SQSTM1 detected in affected tissues from patients with sporadic Paget’s disease of bone. J Bone Miner Res. 2009;24:484–94.PubMedGoogle Scholar
  71. 71.
    Meunier P. La maladie osseuse de Paget – histologie quantitative, histopathogenie et perspectives therapeutiques. Lyon Med. 1975;233:839–53.Google Scholar
  72. 72.
    Meunier P, Ravault A. Treatment of Paget’s disease with etidronate disodium. In: Singer FR, Wallach S, editors. Paget’s Disease of bone, clinical assessment, present and future therapy. New York: Elsevier; 1991. p. 86–99.Google Scholar
  73. 73.
    Meunier PJ, Coindre JM, Edouard CM, Arlot ME. Bone histomorphometry in Paget’s disease. Quantitative and dynamic analysis of pagetic and nonpagetic bone tissue. Arthritis Rheum. 1980;23:1095–103.PubMedGoogle Scholar
  74. 74.
    Meyers MH, Singer FR. Osteotomy for tibia vara in Paget’s disease under cover of calcitonin. J Bone Joint Surg Am. 1978;60:810–4.PubMedGoogle Scholar
  75. 75.
    Michou L, Morissette J, Gagnon ER, Marquis A, Dellabadia M, Brown JP, Siris ES. Novel SQSTM1 mutations in patients with Paget’s disease of bone in an unrelated multiethnic American population. Bone. 2011;48:456–60. Epub 2010 Nov 10.PubMedGoogle Scholar
  76. 76.
    Mills BG, Singer FR. Nuclear inclusions in Paget’s disease of bone. Science. 1976;194:201–2.PubMedGoogle Scholar
  77. 77.
    Mills BG, Singer FR, Weiner LP, Holst PA. Immunohistological demonstration of respiratory syncytial virus antigens in Paget disease of bone. Proc Natl Acad Sci USA. 1981;78:1209–13.PubMedGoogle Scholar
  78. 78.
    Mills BG, Singer FR, Weiner LP, Suffin SC, Stabile E, Holst P. Evidence for both respiratory syncytial virus and measles virus antigens in the osteoclasts of patients with Paget’s disease of bone. Clin Orthop Relat Res. 1984;183:303–11.PubMedGoogle Scholar
  79. 79.
    Mills BG, Yabe H, Singer FR. Osteoclasts in human osteopetrosis contain viral-nucleocapsid-like nuclear inclusions. J Bone Miner Res. 1988;3:101–6.PubMedGoogle Scholar
  80. 80.
    Mirra JM, Brien EW, Tehranzadeh J. Paget’s disease of bone: review with emphasis on radiologic features, part II. Skeletal Radiol. 1995;24:173–84.PubMedGoogle Scholar
  81. 81.
    Morissette J, Laurin N, Brown JP. Sequestosome 1: mutation frequencies, haplotypes, and phenotypes in familial Paget’s disease of bone. J Bone Miner Res. 2006;21 Suppl 2:P38–44.PubMedGoogle Scholar
  82. 82.
    Nathan AW, Ludlam HA, Wilson DW, Dandona P. Hypercalcaemia due to immobilization of a patient with Paget’s disease of bone. Postgrad Med J. 1982;58:714–5.PubMedGoogle Scholar
  83. 83.
    Nuovo MA, Nuovo GJ, MacConnell P, Forde A, Steiner GC. In situ analysis of Paget’s disease of bone for measles-specific PCR-amplified cDNA. Diagn Mol Pathol. 1992;1:256–65.PubMedGoogle Scholar
  84. 84.
    O’Driscoll JB, Anderson DC. Past pets and Paget’s disease. Lancet. 1985;2:919–21.PubMedGoogle Scholar
  85. 85.
    Ooi CG, Walsh CA, Gallagher JA, Fraser WD. Absence of measles virus and canine distemper virus transcripts in long-term bone marrow cultures from patients with Paget’s disease of bone. Bone. 2000;27:417–21.PubMedGoogle Scholar
  86. 86.
    Paget J. On a form of chronic inflammation of bones (osteitis deformans). Med Chir Trans. 1877;60(37–64):39.Google Scholar
  87. 87.
    Poor G, Donath J, Fornet B, Cooper C. Epidemiology of Paget’s disease in Europe: the prevalence is decreasing. J Bone Miner Res. 2006;21:1545–9.PubMedGoogle Scholar
  88. 88.
    Ralston SH. Pathogenesis of Paget’s disease of bone. Clin Rev Bone Miner Metab. 2002;1:109–14.Google Scholar
  89. 89.
    Rebel A, Basle M, Pouplard A, Kouyoumdjian S, Filmon R, Lepatezour A. Viral antigens in osteoclasts from Paget’s disease of bone. Lancet. 1980;2:344–6.PubMedGoogle Scholar
  90. 90.
    Rebel A, Malkani K, Basle M. Nuclear anomalies in osteoclasts in Paget’s bone disease. Nouv Presse Med. 1974;3:1299–301.PubMedGoogle Scholar
  91. 91.
    Reddy SV, Singer FR, Mallette L, Roodman GD. Detection of measles virus nucleocapsid transcripts in circulating blood cells from patients with Paget disease. J Bone Miner Res. 1996;11:1602–7.PubMedGoogle Scholar
  92. 92.
    Reddy SV, Singer FR, Roodman GD. Bone marrow mononuclear cells from patients with Paget’s disease contain measles virus nucleocapsid messenger ribonucleic acid that has mutations in a specific region of the sequence. J Clin Endocrinol Metab. 1995;80:2108–11.PubMedGoogle Scholar
  93. 93.
    Reid I, Lyles K, Su G, Brown J, Walsh J, Del Pino Montes J, Miller P, Fraser W, Gall M, Saidi Y, Bucci-Rechtweg C, Hosking D. Long-term efficacy of zoledronic acid compared with risedronate in Paget’s disease. In: American Society for Bone and Mineral Research 31st annual meeting, Colorado Convention Center, Denver; 2009.Google Scholar
  94. 94.
    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. Comparison of a single infusion of zoledronic acid with risedronate for Paget’s disease. N Engl J Med. 2005;353:898–908.PubMedGoogle Scholar
  95. 95.
    Rhodes EC, Johnson-Pais TL, Singer FR, Ankerst DP, Bruder JM, Wisdom J, Hoon DS, Lin E, Bone HG, Simcic KJ, Leach RJ. Sequestosome 1 (SQSTM1) mutations in Paget’s disease of bone from the United States. Calcif Tissue Int. 2008;82:271–7.PubMedGoogle Scholar
  96. 96.
    Roelofs AJ, Thompson K, Ebetino FH, Rogers MJ, Coxon FP. Bisphosphonates: molecular mechanisms of action and effects on bone cells, monocytes and macrophages. Curr Pharm Des. 2010;16:2950–60.PubMedGoogle Scholar
  97. 97.
    Roodman GD, Kurihara N, Ohsaki Y, Kukita A, Hosking D, Demulder A, Smith JF, Singer FR. Interleukin 6. A potential autocrine/paracrine factor in Paget’s disease of bone. J Clin Invest. 1992;89:46–52.PubMedGoogle Scholar
  98. 98.
    Roohi F, Mann D, Kula RW. Surgical management of hydrocephalic dementia in Paget’s disease of bone: the 6-year outcome of ventriculo-peritoneal shunting. Clin Neurol Neurosurg. 2005;107:325–8.PubMedGoogle Scholar
  99. 99.
    Sauty A, Pecherstorfer M, Zimmer-Roth I, Fioroni P, Juillerat L, Markert M, Ludwig H, Leuenberger P, Burckhardt P, Thiebaud D. Interleukin-6 and tumor necrosis factor alpha levels after bisphosphonates treatment in vitro and in patients with malignancy. Bone. 1996;18:133–9.PubMedGoogle Scholar
  100. 100.
    Schuller A. Dysostosis hypophysaria. Br J Radiol. 1926;31:156–8.Google Scholar
  101. 101.
    Selby PL, Davies M, Mee AP. Canine distemper virus induces human osteoclastogenesis through NF-kappaB and sequestosome 1/P62 activation. J Bone Miner Res. 2006;21:1750–6.PubMedGoogle Scholar
  102. 102.
    Shankar S, Hosking DJ. Biochemical assessment of Paget’s disease of bone. J Bone Miner Res. 2006;21 Suppl 2:P22–7.PubMedGoogle Scholar
  103. 103.
    Shardlow DL, Giannoudis PV, Matthews SJ, Smith RM. Stabilisation of acute femoral fractures in Paget’s disease. Int Orthop. 1999;23:283–5.PubMedGoogle Scholar
  104. 104.
    Singer FR. Human calcitonin treatment of Paget’s disease of bone. Clin Orthop Relat Res. 1977;127:86–93.PubMedGoogle Scholar
  105. 105.
    Singer FR, Fredericks RS, Minkin C. Salmon calcitonin therapy for Paget’s disease of bone. The problem of acquired clinical resistance. Arthritis Rheum. 1980;23:1148–54.PubMedGoogle Scholar
  106. 106.
    Singer FR, Mills BG. Giant cell tumor arising in Paget’s disease of bone. Recurrences after 36 years. Clin Orthop Relat Res. 1993;293:293–301.PubMedGoogle Scholar
  107. 107.
    Singer FR, Mills BG, Gruber HE, Windle JJ, Roodman GD. Ultrastructure of bone cells in Paget’s disease of bone. J Bone Miner Res. 2006;21 Suppl 2:P51–4.PubMedGoogle Scholar
  108. 108.
    Siris E, Weinstein RS, Altman R, Conte JM, Favus M, Lombardi A, Lyles K, McIlwain H, Murphy Jr WA, Reda C, Rude R, Seton M, Tiegs R, Thompson D, Tucci JR, Yates AJ, Zimering M. Comparative study of alendronate versus etidronate for the treatment of Paget’s disease of bone. J Clin Endocrinol Metab. 1996;81:961–7.PubMedGoogle Scholar
  109. 109.
    Siris ES, Chines AA, Altman RD, Brown JP, Johnston Jr CC, Lang R, McClung MR, Mallette LE, Miller PD, Ryan WG, Singer FR, Tucci JR, Eusebio RA, Bekker PJ. Risedronate in the treatment of Paget’s disease of bone: an open label, multicenter study. J Bone Miner Res. 1998;13:1032–8.PubMedGoogle Scholar
  110. 110.
    Siris ES, Kelsey JL, Flaster E, Parker S. Paget’s disease of bone and previous pet ownership in the United States: dogs exonerated. Int J Epidemiol. 1990;19:455–8.PubMedGoogle Scholar
  111. 111.
    Stack R, Tarr K. Drug-induced optic neuritis and uveitis secondary to bisphosphonates. N Z Med J. 2006;119:U1888.PubMedGoogle Scholar
  112. 112.
    Sturtridge WC, Harrison JE, Wilson DR. Long-term treatment of Paget’s disease of bone with salmon calcitonin. Can Med Assoc J. 1977;117:1031–4.PubMedGoogle Scholar
  113. 113.
    Tancioni F, Di Ieva A, Levi D, Aimar E, Debernardi A, Colombo P, Gaetani P, Rodriguez YBR. Spinal decompression and vertebroplasty in Paget’s disease of the spine. Surg Neurol. 2006;66:189–91; discussion 191.PubMedGoogle Scholar
  114. 114.
    Thiebaud D, Jaeger P, Gobelet C, Jacquet AF, Burckhardt P. A single infusion of the bisphosphonate AHPrBP (APD) as treatment of Paget’s disease of bone. Am J Med. 1988;85:207–12.PubMedGoogle Scholar
  115. 115.
    Thompson K, Rogers Ms. Statins prevent bisphosphonate-induced gamma, delta-T-cell proliferation and activation in vitro.V Boneminer Res 2004;19:278–288.PubMedGoogle Scholar
  116. 116.
    Trombetti A, Arlot M, Thevenon S, Vebelhart B Meurler PS. Effect of mutiple intravenous pamidronat courses in Pagetis disease of bone. Rev Rhum Engl Ed. 1999;66:467–476.PubMedGoogle Scholar
  117. 117.
    Visconti MR, Langston AL, Alonso N, Goodman K, Selby PL, Fraser WD, Ralston SH. Mutations of SQSTM1 are associated with severity and clinical outcome in Paget disease of bone. J Bone Miner Res. 2010;25:2368–73.PubMedGoogle Scholar
  118. 118.
    Watts GD, Thomasova D, Ramdeen SK, Fulchiero EC, Mehta SG, Drachman DA, Weihl CC, Jamrozik Z, Kwiecinski H, Kaminska A, Kimonis VE. Novel VCP mutations in inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia. Clin Genet. 2007;72:420–6.PubMedGoogle Scholar
  119. 119.
    Watts GD, Wymer J, Kovach MJ, Mehta SG, Mumm S, Darvish D, Pestronk A, Whyte MP, Kimonis VE. Inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia is caused by mutant valosin-containing protein. Nat Genet. 2004;36:377–81.PubMedGoogle Scholar
  120. 120.
    Weihl CC, Pestronk A, Kimonis VE. Valosin-containing protein disease: inclusion body myopathy with Paget’s disease of the bone and fronto-temporal dementia. Neuromuscul Disord. 2009;19:308–15.PubMedGoogle Scholar
  121. 121.
    Welsh RA, Meyer AT. Nuclear fragmentations and associated fibrils in giant cell tumor of bone. Lab Invest. 1970;22:63–72.PubMedGoogle Scholar
  122. 122.
    Whitson HE, Lobaugh B, Lyles KW. Severe hypocalcemia following bisphosphonate treatment in a patient with Paget’s disease of bone. Bone. 2006;39:954–8.PubMedGoogle Scholar
  123. 123.
    Wootton R, Reeve J, Spellacy E, Tellez-Yudilevich M. Skeletal blood flow in Paget’s disease of bone and its response to calcitonin therapy. Clin Sci Mol Med. 1978;54:69–74.PubMedGoogle Scholar
  124. 124.
    Wuyts W, Van Wesenbeeck L, Morales-Piga A, Ralston S, Hocking L, Vanhoenacker F, Westhovens R, Verbruggen L, Anderson D, Hughes A, Van Hul W. Evaluation of the role of RANK and OPG genes in Paget’s disease of bone. Bone. 2001;28:104–7.PubMedGoogle Scholar
  125. 125.
    Young CA, Fraser WD, Mackenzie IJ. Detection of hearing impairment and handicap in Paget’s disease of bone using a simple scoring system: a case control study. Bone. 2007;40:189–93.PubMedGoogle Scholar

Copyright information

© Springer-Verlag London 2012

Authors and Affiliations

  1. 1.Endocrine/Bone Disease ProgramJohn Wayne Cancer Institute, St. John’s Health CenterSanta MonicaUSA
  2. 2.Department of Medicine, Director of Hematology/OncologyIndiana UniversityIndianapolisUSA

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