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Paget’s disease of bone: epidemiology, pathogenesis and pharmacotherapy

, MD PhD, , MD PhD, , MD, , PhD, , PhD & , MD

Bibliography

  • Paget J. On a form of chronic inflammation of bones (osteitis deformans). Med Chir Trans 1877;60:37-63
  • Kanis J. A pathophysiology and treatment of Paget’s disease of bone. 2nd edition. Martin Dunitz, London; 1998. p. 10
  • Ralston SH. Paget’s Disease of Bone. N Engl J Med 2013;368:644-50
  • Reddy SV, Menaa C, Singer FR, et al. Cell biology of Paget disease. J Bone Miner Res 1999;14:3-8
  • Roodman GD, Windle JJ. Paget disease of bone. J Clin Invest 2005;115:200-8
  • Rebel A, Basle M, Pouplard A, et al. Bone tissue in Paget’s disease of bone: ultrastructure and immunocytology. Arthritis Rheum 1980;23:1104-14
  • Robey PG, Bianco P. The role of osteogenic cells in the pathophysiology of Paget’s disease. J Bone Miner Res 1999;14:9-16
  • Demulder A, Takahashi S, Singer FR, et al. Evidence for abnormalities in osteoclast precursors and the marrow microenvironment in Paget disease. Endocrinology 1993;133:1978-82
  • Mankin HJ, Hornicek FJ. Paget’s sarcoma: A historical and outcome review. Clin Orthop Relat Res 2005;438:97-102
  • Hansen MF, Seton M, Merchant A. Osteosarcoma in Paget’s disease of bone. J Bone Miner Res 2006;21(Suppl 2):P58-63
  • Jacobs TP, Michelsen J, Polay JS, et al. Giant cell tumor in Paget’s disease of bone: familial and geographic clustering. Cancer 1979;44:742-7
  • Huvos AG. Osteogenic sarcoma of bones and soft tissues in older persons. A clinicopathologic analysis of 117 patients older than 60 years. Cancer 1986;57:1442-9
  • Resnick D, Niwayama G. Paget's disease. In: Resnick D, Niwayama G, editors, Diagnosis of bone and joint disorders. Volume 2. W. B. Saunders, Philadelphia, PA, USA; 1981. p. 1721-54
  • Barker DJ. The epidemiology of Paget’s disease. Metab Bone Dis Relat Res 1981;3:231-3
  • Detheridge FM, Guyer PB, Barker DJ. European distribution of Paget’s disease of bone. Br Med J 1982;285:1005-8
  • van Staa TP, Selby P, Leufkens HG, et al. Incidence and natural history of Paget’s disease of bone in England and Wales. J Bone Miner Res 2002;17:465-71
  • Altman RD, Bloch DA, Hochberg MC, Murphy WA. Prevalence of pelvic Paget’s disease of bone in the United States. J Bone Miner Res 2000;15:461-5
  • Cundy T, McAnulty K, Wattie D, et al. Evidence for secular change in Paget’s disease. Bone 1997;20:69-71
  • Cooper C, Schafheutle K, Dennison E, et al. The epidemiology of Paget’s disease in Britain: Is the prevalence decreasing? J Bone Miner Res 1999;14:192-7
  • Cooper C, Harvey NC, Dennison EM, van Staa TP. Update on the epidemiology of Paget’s disease of bone. J Bone Miner Res 2006;21:P3-8
  • Doyle T, Gunn J, Anderson G, et al. Paget’s disease in New Zealand: evidence for declining prevalence. Bone 2002;31:616-19
  • 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
  • Corral-Gudino L, García-Aparicio J, Sánchez-González MD, et al. Secular changes in Paget’s disease: contrasting changes in the number of new referrals and in disease severity in two neighboring regions of Spain. Osteoporos Int 2013;24:443-50
  • Gennari L, Di Stefano M, Merlotti D, et al. Prevalence of Paget’s disease of bone in Italy. J Bone Miner Res 2005;20:1845-50
  • Gennari L, Merlotti D, Martini G, Nuti R. Paget’s disease of bone in Italy. J Bone Miner Res 2006;21(Suppl 2):P14-21
  • Rendina D, Gennari L, De Filippo G, et al. Evidence for increased clinical severity of familial and sporadic Paget’s disease of bone in Campania, southern Italy. J Bone Miner Res 2006;21:1828-35
  • Rendina D, Gianfrancesco F, De Filippo G, et al. Epidemiological, clinical, and genetic characteristics of Paget’s disease of bone in a rural area of Calabria, Southern Italy. J Endocrinol Invest 2010;33:519-25
  • Sankaran S, Naot D, Grey A, Cundy T. Paget’s disease in patients of Asian descent in New Zealand. J Bone Miner Res 2012;27:223-6
  • Barker DJ, Chamberlain AT, Guyer PB, Gardner MJ. Paget’s disease of bone: the Lancashire focus. Br Med J 1980;280:1105-7
  • Merlotti D, Gennari L, Galli B, et al. Characteristics and familial aggregation of Paget’s disease of bone in Italy. J Bone Miner Res 2005;20:1356-64
  • López-Abente G, Morales-Piga A, Bachiller-Corral FJ, et al. Identification of possible areas of high prevalence of Paget’s disease of bone in Spain. Clin Exp Rheumatol 2003;21:635-8
  • Ralston SH, Langston AL, Reid IR. Pathogenesis and management of Paget’s disease of bone. Lancet 2008;372:155-63
  • Singer FR. The etiology of Paget’s disease of bone: viral and genetic interactions. Cell Metab 2011;13:5-6
  • Siris ES, Ottman R, Flaster E, Kelsey JL. Familial aggregation of Paget’s disease of bone. J Bone Miner Res 1991;6:495-500
  • Siris ES. Epidemiological aspects of Paget’s disease: family history and relationship to other medical conditions. Semin Arthritis Rheum 1994;23:222-5
  • Morales-Piga AA, Rey-Rey JS, Corres-González J, et al. Frequency and characteristics of familial aggregation of Paget’s disease of bone. J Bone Miner Res 1995;10:663-70
  • Gardener MJ, Guyer PB, Barker DJ. Radiological prevalence of Paget’s disease of bone in British migrants to Australia. Br Med J 1978;1:1655-7
  • Rebel A, Bregeon C, Basle M, et al. Osteoclastic inclusions in Paget’s disease of bone. Rev Rhum Mal Osteoartic 1942;42:637-41
  • Mills BG, Singer FR. Nuclear inclusions in Paget’s disease of bone. Science 1976;194:201-2
  • Mee AP, Sharpe PT. Dogs, distemper and Paget’s disease. Bioessays 1993;15:783-9
  • López-Abente G, Morales-Piga A, Elena-Ibáñez A, et al. Cattle, pets, and Paget’s disease of bone. Epidemiology 1997;8:247-51
  • Mills BG, Singer FR, Weiner LP, et al. 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
  • Gordon MT, Mee AP, Sharpe PT. Paramyxoviruses in Paget’s disease. Semin Arthritis Rheum 1994;23:232-4
  • Mee AP, Dixon JA, Hoyland JA, et al. 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
  • Ralston SH, Digiovine FS, Gallacher SJ, et al. Failure to detect paramyxovirus sequences in Paget’s disease of bone using polymerase chain reaction. J Bone Miner Res 1991;6:1243-8
  • Birch MA, Taylor W, Fraser WD, et al. Absence of paramyxovirus RNA in cultures of pagetic bone cells and in pagetic bone. J Bone Miner Res 1994;9:11-16
  • 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
  • Ralston SH, Afzal MA, Helfrich MH, et al. Multicenter blinded analysis of RT-PCR detection methods for paramyxoviruses in relation to Paget’s disease of bone. J Bone Miner Res 2007;22:569-77
  • 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
  • Kurihara N, Reddy SV, Menaa C, et al. Osteoclasts expressing the measles virus nucleocapsid gene display pagetic phenotype. J Clin Invest 2000;105:607-14
  • Kurihara N, Zhou H, Reddy SV, et al. 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
  • Barker DJ, Gardner MJ. Distribution of Paget’s disease in England, Wales and Scotland and a possible relationship with vitamin D deficiency in childhood. Br J Prev Soc Med 1974;28:226-32
  • Siris ES. Epidemiological aspects of Paget’s disease: family history and relationship to other medical conditions. Semin Arthritis Rheum 1994;23:222-5
  • Michou L, Collet C, Morissette J, et al. Epidemiogenetic study of French families with Paget’s disease of bone. Joint Bone Spine 2012;79:393-8
  • Lever JH. Paget’s disease of bone in Lancashire and arsenic pesticide in cotton mill wastewater: a speculative hypothesis. Bone 2002;31:434-6
  • Lucas GJ, Daroszewska A, Ralston SH. Contribution of genetic factors to the pathogenesis of Paget’s disease of bone and related disorders. J Bone Miner Res 2006;21(Suppl 2):31-7
  • Whyte MP. Paget’s disease of bone and genetic disorders of RANKL/OPG/RANK/NF-kappaB signaling. Ann NY Acad Sci 2006;1068:143-64
  • Ralston SH, Layfield R. Pathogenesis of Paget disease of bone. Calcif Tissue Int 2012;91(2):97-113
  • 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
  • Hocking LJ, Lucas GJ, Daroszewska A, et al. Domain specific mutations in Sequestosome 1 (SQSTM1) cause familial and sporadic Paget’s disease. Hum Mol Genet 2002;11:2735-9
  • Ralston SH, Albagha OM. Genetic determinants of Paget’s disease of bone. Ann NY Acad Sci 2011;1240:53-60
  • Falchetti A, Di Stefano M, Marini F, et al. Genetic epidemiology of Paget’s disease of bone in Italy: sequestosome1/p62 gene mutational test and haplotype analysis at 5q35 in a large representative series of sporadic and familial Italian cases of Paget’s disease of bone. Calcif Tissue Int 2009;84:20-37
  • Gennari L, Gianfrancesco F, Di Stefano M, et al. SQSTM1 gene analysis and gene-environment interaction in Paget’s disease of bone. J Bone Miner Res 2010;25:1375-84
  • Garner TP, Long J, Layfield R, Searle MS. Impact of p62/SQSTM1 UBA domain mutations linked to Paget’s disease of bone on ubiquitin recognition. Biochemistry 2011;50:4665-74
  • Rea SL, Walsh JP, Ward L, et al. A novel mutation (K378X) in the sequestosome 1 gene associated with increased NF-kappaB signaling and Paget’s disease of bone with a severe phenotype. J Bone Miner Res 2006;21:1136-45
  • Jin W, Chang M, Paul EM, et al. Deubiquitinating enzyme CYLD negatively regulates RANK signaling and osteoclastogenesis in mice. J Clin Invest 2008;118:1858-66
  • Sundaram K, Shanmugarajan S, Rao DS, Reddy SV. Mutant p62P392L stimulation of osteoclast differentiation in Paget’s disease of bone. Endocrinology 2011;152:4180-9
  • Visconti MR, Langston AL, Alonso N, et al. Mutations of SQSTM1 are associated with severity and clinical outcome in Paget’s disease of bone. J Bone Miner Res 2010;25:2368-73
  • Albagha OM, Visconti MR, Alonso N, et al. Common susceptibility alleles and SQSTM1 mutations predict disease extent and severity in a multinational study of patients with Paget’s disease. J Bone Miner Res 2013;28:2338-46
  • Leach RJ, Singer FR, Ench Y, et al. Clinical and cellular phenotypes associated with sequestosome 1 (SQSTM1) mutations. J Bone Miner Res 2006;21(Suppl 2):P45-50
  • Bolland MJ, Tong PC, Naot D, et al. Delayed development of Paget’s disease in offspring inheriting SQSTM1 mutations. J Bone Miner Res 2007;22:411-15
  • Kurihara N, Hiruma Y, Zhou H, et al. Mutation of the sequestosome 1 (p62) gene increases osteoclastogenesis but does not induce Paget disease. J Clin Invest 2007;117:133-42
  • Hiruma Y, Kurihara N, Subler MA, et al. A SQSTM1/p62 mutation linked to Paget’s disease increases the osteoclastogenic potential of the bone microenvironment. Hum Mol Genet 2008;23:3708-19
  • Daroszewska A, van ’t Hof RJ, Rojas JA, et al. A point mutation in the ubiquitin-associated domain of SQSMT1 is sufficient to cause a Paget’s disease-like disorder in mice. Hum Mol Genet 2011;20:2734-44
  • Kurihara N, Hiruma Y, Yamana K, et al. Contributions of the measles virus nucleocapsid gene and the SQSTM1/p62(P392L) mutation to Paget’s disease. Cell Metab 2011;13:23-34
  • Albagha OM, Visconti MR, Alonso N, et al. 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
  • Albagha OM, Wani SE, Visconti MR, et al. Genetic Determinants of Paget’s Disease(GDPD) Consortium. Genome-wide association identifies three new susceptibility loci for Paget’s disease of bone. Nat Genet 2011;43:685-9
  • Gianfrancesco F, Rendina D, Di Stefano M, et al. A nonsynonymous TNFRSF11A variation increases NFκB activity and the severity of Paget’s disease. J Bone Miner Res 2012;27:443-52
  • Kimonis VE, Fulchiero E, Vesa J, Watts G. VCP disease associated with myopathy, Paget disease of bone and frontotemporal dementia: review of a unique disorder. Biochim Biophys Acta 2008;1782:744-8
  • Jacobs TP, Michelsen J, Polay JS, et al. Giant cell tumor in Paget’s disease of bone: familial and geographic clustering. Cancer 1979;44:742-7
  • Watts GD, Wymer J, Kovach MJ, et al. 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
  • Gianfrancesco F, Rendina D, Merlotti D, et al. Giant cell tumor occurring in familial Paget’s disease of bone: report of clinical characteristics and linkage analysis of a large pedigree. J Bone Miner Res 2013;28:341-50
  • Merlotti D, Gennari L, Martini G, et al. Current options for the treatment of Paget’s disease of the bone. Open Access Rheumatol 2009;1:107-20
  • Gennari L, Merlotti D, Mossetti G, et al. The use of intravenous aminobisphosphonates for the treatment of Paget’s disease of bone. Mini Rev Med Chem 2009;9:1052-63
  • Siris ES, Lyles KW, Singer FR, Meunier PJ. Medical management of Paget’s disease of bone: implications for treatment and review of current therapies. J Bone Miner Res 2006;21:94-7
  • Siris ES, Feldman F. Natural history of untreated Paget’s disease of the tibia. J Bone Miner Res 1997;12:691-2
  • Meunier PJ, Vignot E. Therapeutic strategy in Paget’s disease of bone. Bone 1995;17:489S-91S
  • Bickerstaff DR, Douglas DL, Burke PH, et al. Improvement in facial deformity of Paget disease treated with diphosphonates. J Bone Joint Surg Br 1990;72:132-6
  • Murdin LM, Yeoh LH. Hearing loss treated with pamidronate. J R Soc Med 2005;98:272-4
  • Russell G. Bisphosphonates from bench to bedside. Ann NY Acad Sci 2006;1068:367-401
  • Papapoulos SE, Eekhoff EM, Zwinderman AH. Acquired resistance to bisphosphonates in Paget’s disease of bone. J Bone Miner Res 2006;21:88-91
  • Boyce BF, Adamson BB, Gallacher SJ, et al. Mineralization defects after pamidronate for Paget disease. Lancet 1994;343:1231-2
  • Buckler HM, Mercer SJ, Davison CE, et al. Evaluation of adverse experiences related to pamidronate infusion in Paget disease of bone. Ann Rheum Dis 1998;57:572
  • Reid IR, Miller P, Lyles K, et al. Comparison of a single infusion of zoledronic acid with risedronate for Paget’s disease. N Engl J Med 2005;353:898-908
  • Reid IR, Lyles K, Su G, et al. A single infusion of zoledronic acid produces sustained remissions in Paget disease: data to 6.5 years. J Bone Miner Res 2011;26:2261-70
  • Merlotti D, Gennari L, Martini G, et al. Comparison of different intravenous bisphosphonate regimens for Paget’s disease of bone. J Bone Miner Res 2007;22:1510-17
  • Merlotti D, Rendina D, Gennari L, et al. Comparison of intravenous and intramuscular neridronate regimens for the treatment of Paget disease of bone. J Bone Miner Res 2011;26:512-18
  • Reid IR, Gamble GD, Mesenbrink P, et al. Characterization of and risk factors for the acute-phase response after zoledronic acid. J Clin Endocrinol Metab 2010;95:4380.7
  • Abrahamsen B. Adverse effects of bisphosphonates. Calcif Tissue Int 2010;86:421-35
  • Miller PD, Jamal SA, Evenepoel P, et al. Renal safety in patients treated with bisphosphonates for osteoporosis: a review. J Bone Miner Res 2013;28:2049-59
  • Rea SL, Walsh JP, Layfield R, et al. New insights into the role of sequestosome 1/p62 mutant proteins in the pathogenesis of Paget’s disease of bone. Endocr Rev 2013;34:501-24
  • Geetha T, Vishwaprakash N, Sycheva M, Babu JR. Sequestosome 1/p62: across diseases. Biomarkers 2012;17:99-103
  • Rodriguez A, Durán A, Selloum M, et al. Mature-onset obesity and insulin resistance in mice deficient in the signaling adapter p62. Cell Metab 2006;3:211-22
  • Ramesh Babu J, Lamar Seibenhener M, Peng J, et al. Genetic inactivation of p62 leads to accumulation of hyperphosphorylated tau and neurodegeneration. J Neurochem 2008;106:107-20
  • Sugimoto R, Warabi E, Katayanagi S, et al. Enhanced neointimal hyperplasia and carotid artery remodelling in sequestosome 1 deficient mice. J Cell Mol Med 2010;14:1546-54
  • Fecto F, Yan J, Vemula SP, et al.; SQSTM1 mutations in familial and sporadic amyotrophic lateral sclerosis. Arch Neurol 2011;68:1440-6
  • Rubino E, Rainero I, Chiò A, et al. TODEM Study Group. SQSTM1 mutations in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Neurology 2012;79:1556-62
  • Le Ber I, Camuzat A, Guerreiro R, et al.; French Clinical and Genetic Research Network on FTD/FTD-ALS. SQSTM1 mutations in French patients with frontotemporal dementia or frontotemporal dementia with amyotrophic lateral sclerosis. JAMA Neurol 2013;70:1403-10
  • Kwok CT, Morris A, de Belleroche JS. Sequestosome-1 (SQSTM1) sequence variants in ALS cases in the UK: prevalence and coexistence of SQSTM1 mutations in ALS kindred with PDB. Eur J Hum Genet 2013. [Epub ahead of print]
  • Chen Y, Zheng ZZ, Chen X, et al. SQSTM1 mutations in Han Chinese populations with sporadic amyotrophic lateral sclerosis. Neurobiol Aging 2014;35:726.e7-9

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