osteitis deformans

Summary

Summary: A disease marked by repeated episodes of increased bone resorption followed by excessive attempts at repair, resulting in weakened, deformed bones of increased mass. The resultant architecture of the bone assumes a mosaic pattern in which the fibers take on a haphazard pattern instead of the normal parallel symmetry.

Top Publications

  1. Albagha O, Wani S, Visconti M, Alonso N, Goodman K, Brandi M, et al. Genome-wide association identifies three new susceptibility loci for Paget's disease of bone. Nat Genet. 2011;43:685-9 pubmed publisher
    ..40, P = 7.38 × 10(-17)) with PDB. These seven loci explained ?13% of the familial risk of PDB. These studies provide new insights into the genetic architecture and pathophysiology of PDB. ..
  2. Ritson G, Custer S, Freibaum B, Guinto J, Geffel D, Moore J, et al. TDP-43 mediates degeneration in a novel Drosophila model of disease caused by mutations in VCP/p97. J Neurosci. 2010;30:7729-39 pubmed publisher
    ..We suggest that these findings are likely relevant to the pathogenic mechanism of a broad array of TDP-43 proteinopathies, including frontotemporal lobar degeneration and amyotrophic lateral sclerosis. ..
  3. Cavey J, Ralston S, Sheppard P, Ciani B, Gallagher T, Long J, et al. Loss of ubiquitin binding is a unifying mechanism by which mutations of SQSTM1 cause Paget's disease of bone. Calcif Tissue Int. 2006;78:271-7 pubmed
  4. Fernández Sáiz V, Buchberger A. Imbalances in p97 co-factor interactions in human proteinopathy. EMBO Rep. 2010;11:479-85 pubmed publisher
    ..Our results suggest that imbalanced co-factor binding to p97 is a key pathological feature of IBMPFD and potentially of other proteinopathies involving p97. ..
  5. Beyens G, Wuyts W, Cleiren E, de Freitas F, Tiegs R, Van Hul W. Identification and molecular characterization of a novel splice-site mutation (G1205C) in the SQSTM1 gene causing Paget's disease of bone in an extended American family. Calcif Tissue Int. 2006;79:281-8 pubmed
    ..PDB mutations that disrupt the function of the PEST domain of SQSTM1 have not been reported before, so probably the pathogenic effect of both transcripts resides in the disruption of the ubiquitin-binding properties of the protein. ..
  6. Vesa J, Su H, Watts G, Krause S, Walter M, Martin B, et al. Valosin containing protein associated inclusion body myopathy: abnormal vacuolization, autophagy and cell fusion in myoblasts. Neuromuscul Disord. 2009;19:766-72 pubmed publisher
  7. Wermers R, Tiegs R, Atkinson E, Achenbach S, Melton L. Morbidity and mortality associated with Paget's disease of bone: a population-based study. J Bone Miner Res. 2008;23:819-25 pubmed publisher
    ..Compared with white Minnesota residents, overall survival was slightly better than expected (p = 0.010). No clinical risk factors were identified that were associated with an increased risk of death. ..
  8. Kurihara N, Hiruma Y, Yamana K, Michou L, Rousseau C, Morissette J, 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 pubmed publisher
    ..Mice coexpressing MVNP and p62(P394L) developed dramatic Paget's-like bone lesions. These results suggest that p62(P394L) and IL-6 induction by MVNP play key roles in PD. ..
  9. Ralston S. Pathogenesis of Paget's disease of bone. Bone. 2008;43:819-25 pubmed publisher

More Information

Publications85

  1. Corral Gudino L, Borao Cengotita Bengoa M, del Pino Montes J, Ralston S. Epidemiology of Paget's disease of bone: a systematic review and meta-analysis of secular changes. Bone. 2013;55:347-52 pubmed publisher
    ..Search terms included epidemiology, incidence, prevalence, cohort studies, osteitis deformans or Paget's disease of bone. Studies with incidence and/or prevalence rate for PDB were included...
  2. Daroszewska A, Ralston S. Mechanisms of disease: genetics of Paget's disease of bone and related disorders. Nat Clin Pract Rheumatol. 2006;2:270-7 pubmed
  3. Magnusson P, Davie M, Sharp C. Circulating and tissue-derived isoforms of bone alkaline phosphatase in Paget's disease of bone. Scand J Clin Lab Invest. 2010;70:128-35 pubmed publisher
    ..The bone ALP isoform B2 may be of use in the management of PDB but that has to be further elucidated in subsequent studies. ..
  4. Kurihara N, Hiruma Y, Zhou H, Subler M, Dempster D, Singer F, et al. Mutation of the sequestosome 1 (p62) gene increases osteoclastogenesis but does not induce Paget disease. J Clin Invest. 2007;117:133-42 pubmed
  5. Hosking D, Lyles K, Brown J, Fraser W, Miller P, Curiel M, et al. Long-term control of bone turnover in Paget's disease with zoledronic acid and risedronate. J Bone Miner Res. 2007;22:142-8 pubmed
    ..A reduction in the incidence and severity of long-term complications may require persistent normalization of bone turnover over many years, and this now seems a realistic possibility with ZOL. ..
  6. Takata S, Hashimoto J, Nakatsuka K, Yoshimura N, Yoh K, Ohno I, et al. Guidelines for diagnosis and management of Paget's disease of bone in Japan. J Bone Miner Metab. 2006;24:359-67 pubmed
    ..Indications for surgical intervention in PDB include unstable fractures, osteoarthritis, malignant soft-tissue tumor, osteosarcoma, and bone deformity. ..
  7. Preziosi R, Diana A, Florio D, Gustinelli A, Nardini G. Osteitis deformans (Paget's disease) in a Burmese python (Python molurus bivittatus)--a case report. Vet J. 2007;174:669-72 pubmed
    b>Osteitis deformans (Paget's disease of bone) is a chronic focal disorder of bone remodelling characterized by an initial increase in osteoclast-mediated bone resorption, with subsequent compensatory increase in new bone formation, ..
  8. Neumann M, Mackenzie I, Cairns N, Boyer P, Markesbery W, Smith C, et al. TDP-43 in the ubiquitin pathology of frontotemporal dementia with VCP gene mutations. J Neuropathol Exp Neurol. 2007;66:152-7 pubmed
    ..TDP-43 is a common pathologic substrate linking a variety of distinct patterns of FTLD-U pathology caused by different genetic alterations...
  9. Forman M, Mackenzie I, Cairns N, Swanson E, Boyer P, Drachman D, et al. Novel ubiquitin neuropathology in frontotemporal dementia with valosin-containing protein gene mutations. J Neuropathol Exp Neurol. 2006;65:571-81 pubmed
    ..Our findings are consistent with the hypothesis that the pathology associated with VCP gene mutations is the result of impairment of ubiquitin-based degradation pathways...
  10. Shankar S, Hosking D. Biochemical assessment of Paget's disease of bone. J Bone Miner Res. 2006;21 Suppl 2:P22-7 pubmed
    ..This is important because the duration of remission of disease activity is strongly determined by the post treatment nadir bone turnover. ..
  11. Josse R, Hanley D, Kendler D, Ste Marie L, Adachi J, Brown J. Diagnosis and treatment of Paget's disease of bone. Clin Invest Med. 2007;30:E210-23 pubmed
    ..The Panel recommends treating PDB with bisphosphonates that have demonstrated superior efficacy and remission rates. ..
  12. Haddaway M, Davie M, McCall I, Howdle S. Effect of age and gender on the number and distribution of sites in Paget's disease of bone. Br J Radiol. 2007;80:532-6 pubmed
    ..The lesser involvement at the axial sites in monostotic disease may lead to overestimation of the decline in PDB based on abdominal radiographs. ..
  13. Visconti M, Langston A, Alonso N, Goodman K, Selby P, Fraser W, et al. Mutations of SQSTM1 are associated with severity and clinical outcome in paget disease of bone. J Bone Miner Res. 2010;25:2368-73 pubmed publisher
  14. Cundy T, Bolland M. Paget disease of bone. Trends Endocrinol Metab. 2008;19:246-53 pubmed publisher
    ..Most observations seem to fit best with the idea that Paget disease behaves as a multifocal benign neoplasm. ..
  15. Custer S, Neumann M, Lu H, Wright A, Taylor J. 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 pubmed publisher
    ..In vitro studies indicate that mutant VCP causes inappropriate activation of the NF-kappaB signaling cascade, which could contribute to the mechanism of pathogenesis in multiple tissues including muscle, bone and brain...
  16. Rea S, Walsh J, Ward L, Magno A, Ward B, Shaw B, et al. Sequestosome 1 mutations in Paget's disease of bone in Australia: prevalence, genotype/phenotype correlation, and a novel non-UBA domain mutation (P364S) associated with increased NF-kappaB signaling without loss of ubiquitin binding. J Bone Miner Res. 2009;24:1216-23 pubmed publisher
    ..This suggests that increased NF-kappaB signaling, but not the impairment of ubiquitin binding, may be essential in the pathogenesis of PDB associated with SQSTM1 mutations...
  17. Devogelaer J, Bergmann P, Body J, Boutsen Y, Goemaere S, Kaufman J, et al. Management of patients with Paget's disease: a consensus document of the Belgian Bone Club. Osteoporos Int. 2008;19:1109-17 pubmed publisher
    ..Its therapeutic efficacy, its long-term effect on biologic activity and its good tolerance currently supports its use as a first-line therapeutic option in patients suffering from PDB...
  18. Selby P, Davies M, Mee A. Canine distemper virus induces human osteoclastogenesis through NF-kappaB and sequestosome 1/P62 activation. J Bone Miner Res. 2006;21:1750-6 pubmed
    ..We studied the effects of CDV on osteoclastogenesis in vitro and showed that CDV had a dose-dependent effect on osteoclastogenesis, through a possible mechanism involving activation of NF-kappaB and sequestosome 1/p62...
  19. Cundy T. Is Paget's disease of bone disappearing?. Skeletal Radiol. 2006;35:350-1 pubmed
  20. Nagy Z, Gergely P, Donath J, Borgulya G, Csanád M, Poor G. Gene expression profiling in Paget's disease of bone: upregulation of interferon signaling pathways in pagetic monocytes and lymphocytes. J Bone Miner Res. 2008;23:253-9 pubmed publisher
    ..We found a significant overexpression of the genes of the IFN pathway along with a downregulation of tnf-alpha. Our result suggest that IFN-mediated signaling may play important roles in aberrant osteoclastogenesis of PD...
  21. Kimonis V, 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 pubmed publisher
    ..Inclusions seen in the muscle, brain and heart in VCP disease contain ubiquitin, beta amyloid and TDP-43, also seen in other neurodegenerative disorders thus implicating common pathways in their pathogenesis...
  22. Djamshidian A, Schaefer J, Haubenberger D, Stogmann E, Zimprich F, Auff E, et al. A novel mutation in the VCP gene (G157R) in a German family with inclusion-body myopathy with Paget disease of bone and frontotemporal dementia. Muscle Nerve. 2009;39:389-91 pubmed publisher
    ..Two family members also showed signs of early hearing impairment, which was confirmed to be sensorineural in one person, a symptom not yet described in the context of IBMPFD...
  23. Tresse E, Salomons F, Vesa J, Bott L, Kimonis V, Yao T, et al. VCP/p97 is essential for maturation of ubiquitin-containing autophagosomes and this function is impaired by mutations that cause IBMPFD. Autophagy. 2010;6:217-27 pubmed
    ..We conclude that VCP is essential for maturation of ubiquitin-containing autophagosomes and that defect in this function may contribute to IBMPFD pathogenesis...
  24. Albagha O, Visconti M, Alonso N, Langston A, Cundy T, Dargie R, 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 pubmed publisher
    ..09 x 10(-13)) and with rs3018362 on 18q21 near the TNFRSF11A gene (P = 5.27 x 10(-13)). These studies provide new insights into the pathogenesis of PDB and identify OPTN, CSF1 and TNFRSF11A as candidate genes for disease susceptibility...
  25. Kim E, Park Y, Kim D, Ahn B, Kim H, Chang Y, et al. Inclusion body myopathy with Paget disease of bone and frontotemporal dementia linked to VCP p.Arg155Cys in a Korean family. Arch Neurol. 2011;68:787-96 pubmed publisher
    ..Missense mutations in the valosin-containing protein (VCP) gene on chromosome 9p13.3-p12 cause inclusion body myopathy with Paget disease of bone and frontotemporal dementia (hereafter referred to as IBMPFD; OMIM 167320)...
  26. Naot D, Bava U, Matthews B, Callon K, Gamble G, Black M, et al. Differential gene expression in cultured osteoblasts and bone marrow stromal cells from patients with Paget's disease of bone. J Bone Miner Res. 2007;22:298-309 pubmed
    ..We identified several differentially regulated genes, and we suggest that these changes could lead to the formation of the lesions...
  27. Bolland M, Tong P, Naot D, Callon K, Wattie D, Gamble G, et al. Delayed development of Paget's disease in offspring inheriting SQSTM1 mutations. J Bone Miner Res. 2007;22:411-5 pubmed
    ..At any given age, the offspring were less likely to be diagnosed with Paget's disease and had less severe disease than their parents...
  28. Goode A, Layfield R. Recent advances in understanding the molecular basis of Paget disease of bone. J Clin Pathol. 2010;63:199-203 pubmed publisher
  29. Falchetti A, Di Stefano M, Marini F, Ortolani S, Ulivieri M, Bergui S, 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 pubmed publisher
    ..This may be helpful in estimating the true rate of de novo mutations. We confirm the data on the existence of both a mutational hotspot at the UBA domain of SQSTM1/p62 and a founder effect in the PDB population...
  30. Daroszewska A, van t Hof R, Rojas J, Layfield R, Landao Basonga E, Rose L, 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 pubmed publisher
    ..These studies demonstrate that SQSTM1 mutations can cause a PDB-like skeletal disorder in the absence of an additional trigger and provide a new disease model for PDB...
  31. Selby P. Guidelines for the diagnosis and management of Paget's disease: a UK perspective. J Bone Miner Res. 2006;21 Suppl 2:P92-3 pubmed
  32. Nalbandian A, Donkervoort S, Dec E, Badadani M, Katheria V, Rana P, et al. The multiple faces of valosin-containing protein-associated diseases: inclusion body myopathy with Paget's disease of bone, frontotemporal dementia, and amyotrophic lateral sclerosis. J Mol Neurosci. 2011;45:522-31 pubmed publisher
    ..In this review, we will explore the pathogenesis and clinical phenotype of IBMPFD caused by VCP mutations...
  33. Cooper C, Harvey N, Dennison E, van Staa T. Update on the epidemiology of Paget's disease of bone. J Bone Miner Res. 2006;21 Suppl 2:P3-8 pubmed
    ..2; 95% CI, 1.0-1.5). Using life table methodology, the estimated proportion of patients dying within 5 years of follow-up was 32.7% among the cohort with PDB compared with 28.0% among control patients (p < 0.05)...
  34. Riches P, Imanishi Y, Nakatsuka K, Ralston S. Clinical and biochemical response of TNFRSF11A-mediated early-onset familial Paget disease to bisphosphonate therapy. Calcif Tissue Int. 2008;83:272-5 pubmed publisher
    ..The long-term clinical effects of treatment on the natural history of the bone disease remain uncertain however, and this will require further study...
  35. Ralston S, Langston A, Reid I. Pathogenesis and management of Paget's disease of bone. Lancet. 2008;372:155-63 pubmed publisher
    ..No firm evidence as yet exists to show that bisphosphonates can prevent the development of complications of Paget's disease of bone, and further work is needed to address the effects of treatment on long-term clinical outcome...
  36. Wright T, Rea S, Goode A, Bennett A, Ratajczak T, Long J, et al. The S349T mutation of SQSTM1 links Keap1/Nrf2 signalling to Paget's disease of bone. Bone. 2013;52:699-706 pubmed publisher
    ..Thus, SQSTM1-mediated dysregulation of the Keap1-Nrf2 axis, which could potentially lead to aberrant production of oxidative response genes, may contribute to disease aetiology in a subset of PDB patients. ..
  37. Nalbandian A, Llewellyn K, Badadani M, Yin H, Nguyen C, Katheria V, et al. A progressive translational mouse model of human valosin-containing protein disease: the VCP(R155H/+) mouse. Muscle Nerve. 2013;47:260-70 pubmed publisher
    ..More recently, these mutations have been linked to 2% of familial amyotrophic lateral sclerosis (ALS) cases. A knock-in mouse model offers the opportunity to study VCP-associated pathogenesis...
  38. Rendina D, Gennari L, De Filippo G, Merlotti D, De Campora E, Fazioli F, 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 pubmed
    ..A prevalent involvement of the spine and the skull, the sites preferentially involved in giant cell tumors complicating Paget's disease, was also shown in familial cases from this geographical region...
  39. Rea S, Walsh J, Ward L, Yip K, Ward B, Kent G, 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 pubmed
    ..p62 mutants increased NF-kappaB activation and significantly potentiated osteoclast formation and bone resorption in human primary cell cultures...
  40. Stojkovic T, Hammouda E, Richard P, Lopez de Munain A, Ruiz Martinez J, Camaño P, et al. Clinical outcome in 19 French and Spanish patients with valosin-containing protein myopathy associated with Paget's disease of bone and frontotemporal dementia. Neuromuscul Disord. 2009;19:316-23 pubmed publisher
    ..We observed intrafamilial and interfamilial variability in terms of severity, distribution of weakness and presence or not of Paget's disease or cognitive impairment...
  41. Michou L, Morissette J, Gagnon E, Marquis A, DellaBadia M, Brown J, et al. Novel SQSTM1 mutations in patients with Paget's disease of bone in an unrelated multiethnic American population. Bone. 2011;48:456-60 pubmed publisher
    ..The SQSTM1 mutation rate in unrelated American patients described in the present study was similar to that reported in European populations...
  42. Corral Gudino L, del Pino Montes J, García Aparicio J, Alonso Garrido M, Gonzalez Sarmiento R. Paget's disease of bone is not associated with common polymorphisms in interleukin-6, interleukin-8 and tumor necrosis factor alpha genes. Cytokine. 2010;52:146-50 pubmed publisher
    ..Cytokines, specially interleukin (IL)-6, play an important role in the differentiation and activation of osteoclasts and might be involved in osteoblast stimulation in Paget's disease of bone (PDB)...
  43. Ralston S, Afzal M, Helfrich M, Fraser W, Gallagher J, Mee A, 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 pubmed
  44. Ju J, Fuentealba R, Miller S, Jackson E, Piwnica Worms D, Baloh R, et al. Valosin-containing protein (VCP) is required for autophagy and is disrupted in VCP disease. J Cell Biol. 2009;187:875-88 pubmed publisher
    ..These data implicate VCP in autophagy and suggest that impaired autophagy explains the pathology seen in IBMPFD muscle, including TDP-43 accumulation...
  45. Chung P, Beyens G, de Freitas F, Boonen S, Geusens P, Vanhoenacker F, et al. Indications for a genetic association of a VCP polymorphism with the pathogenesis of sporadic Paget's disease of bone, but not for TNFSF11 (RANKL) and IL-6 polymorphisms. Mol Genet Metab. 2011;103:287-92 pubmed publisher
    ..e. TNFRSF11A, CSF1, OPTN and TM7SF4), independent effect of each gene region was found and the cumulative population attributable risk is 72.7%...
  46. Whyte M. Clinical practice. Paget's disease of bone. N Engl J Med. 2006;355:593-600 pubmed
  47. Seton M, Moses A, Bode R, Schwartz C. Paget's disease of bone: the skeletal distribution, complications and quality of life as perceived by patients. Bone. 2011;48:281-5 pubmed publisher
    ..Paget's disease of bone (PDB) is a focal disorder of bone metabolism with overgrowth of affected bone resulting in the skeletal complications of this disease...
  48. Langston A, Campbell M, Fraser W, MacLennan G, Selby P, Ralston S. Randomized trial of intensive bisphosphonate treatment versus symptomatic management in Paget's disease of bone. J Bone Miner Res. 2010;25:20-31 pubmed publisher
    ..Neither management strategy had a significant beneficial impact on pain or quality of life (Clinical trial registration number ISRCTN12989577)...
  49. Cundy T. Is the prevalence of Paget's disease of bone decreasing?. J Bone Miner Res. 2006;21 Suppl 2:P9-13 pubmed
    ..Paget's disease has become less prevalent and patients are presenting later, with less severe disease than previously. These data suggest that environmental factors are important in the etiology of Paget's disease...
  50. Beyens G, Daroszewska A, de Freitas F, Fransen E, Vanhoenacker F, Verbruggen L, et al. 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 pubmed
    ..We observed no association in men, but a highly significant association was found in women, and this was confirmed in a population from the United Kingdom...
  51. Long J, Gallagher T, Cavey J, Sheppard P, Ralston S, Layfield R, et al. Ubiquitin recognition by the ubiquitin-associated domain of p62 involves a novel conformational switch. J Biol Chem. 2008;283:5427-40 pubmed
    ..The conformational switch observed on binding may represent a novel mechanism that underlies specificity in regulating signalinduced protein recognition events...
  52. Collet C, Michou L, Audran M, Chasseigneaux S, Hilliquin P, Bardin T, et al. 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 pubmed
    ..Clinical data indicate that PDB patients with SQSTM1 mutation are younger at PDB diagnosis and have more extensive bone lesions...
  53. Kimonis V, Mehta S, Fulchiero E, Thomasova D, Pasquali M, Boycott K, et al. Clinical studies in familial VCP myopathy associated with Paget disease of bone and frontotemporal dementia. Am J Med Genet A. 2008;146A:745-57 pubmed publisher
    ..The presence of PDB in 28 (57%) individuals suggests that measuring serum alkaline phosphatase (ALP) activity may be a useful screen for IBMPFD in patients with myopathy...
  54. Gianfrancesco F, Rendina D, Di Stefano M, Mingione A, Esposito T, Merlotti D, et al. A nonsynonymous TNFRSF11A variation increases NF?B activity and the severity of Paget's disease. J Bone Miner Res. 2012;27:443-52 pubmed publisher
    ..These results provide the first evidence that genetic variation within the OPG/RANK/RANKL system influences the severity of PBD in synergistic action with SQSTM1 gene mutations...
  55. Heinen C, Garner T, Long J, Böttcher C, Ralston S, Cavey J, et al. Mutant p62/SQSTM1 UBA domains linked to Paget's disease of bone differ in their abilities to function as stabilization signals. FEBS Lett. 2010;584:1585-90 pubmed publisher
    ..These data suggest that the protective effect of UBA domains depends on their structural integrity rather than ubiquitin binding capabilities...
  56. Gennari L, Gianfrancesco F, Di Stefano M, Rendina D, Merlotti D, Esposito T, et al. SQSTM1 gene analysis and gene-environment interaction in Paget's disease of bone. J Bone Miner Res. 2010;25:1375-84 pubmed publisher
    ..84 +/- 2.5 versus 2.76 +/- 2.2, p < .05). Overall, these data suggest that animal-related factors may be important in the etiology of PDB and may interact with SQSTM1 mutations in influencing disease severity...
  57. Singer F. Paget disease: when to treat and when not to treat. Nat Rev Rheumatol. 2009;5:483-9 pubmed publisher
    ..Future studies are needed to determine whether these drugs, if used in an early stage of the disease, can prevent complications in asymptomatic patients...
  58. Marshall M, Evans S, Sharp C, Powell D, McCarthy H, Davie M. Increased circulating Dickkopf-1 in Paget's disease of bone. Clin Biochem. 2009;42:965-9 pubmed publisher
    ..Dkk-1 over-production is implicated in osteolytic disease where it inhibits bone formation and stimulates bone breakdown. Recently it was reported that osteoblastic cells from Paget's disease of bone (PDB) over-expressed Dkk-1...
  59. Weihl C, Pestronk A, Kimonis V. Valosin-containing protein disease: inclusion body myopathy with Paget's disease of the bone and fronto-temporal dementia. Neuromuscul Disord. 2009;19:308-15 pubmed publisher
  60. Whitson H, Lobaugh B, Lyles K. Severe hypocalcemia following bisphosphonate treatment in a patient with Paget's disease of bone. Bone. 2006;39:954-8 pubmed
    ..Physicians should be aware of the potential for hypocalcemia when patients with polyostotic Paget's disease and markedly elevated indicators of bone remodeling are initiated on powerful anti-resorptive therapy...
  61. Hiruma Y, Kurihara N, Subler M, Zhou H, Boykin C, Zhang H, et al. A SQSTM1/p62 mutation linked to Paget's disease increases the osteoclastogenic potential of the bone microenvironment. Hum Mol Genet. 2008;17:3708-19 pubmed publisher
    ..These results indicate that this PDB-associated p62 mutation is not sufficient to induce PDB and suggest that additional factors acting together with p62 mutation are necessary for the development of PDB in vivo...
  62. Najat D, Garner T, Hagen T, Shaw B, Sheppard P, Falchetti A, et al. Characterization of a non-UBA domain missense mutation of sequestosome 1 (SQSTM1) in Paget's disease of bone. J Bone Miner Res. 2009;24:632-42 pubmed publisher
  63. Papapoulos S, Eekhoff E, Zwinderman A. Acquired resistance to bisphosphonates in Paget's disease of bone. J Bone Miner Res. 2006;21 Suppl 2:P88-91 pubmed
  64. Hübbers C, Clemen C, Kesper K, Böddrich A, Hofmann A, Kämäräinen O, et al. Pathological consequences of VCP mutations on human striated muscle. Brain. 2007;130:381-93 pubmed
    ..The latter findings provide a novel link to VCP carbohydrate interactions in the complex pathology of IBMPFD...
  65. Chang Y, Hung W, Chang Y, Chang H, Wu C, Chiang A, et al. Pathogenic VCP/TER94 alleles are dominant actives and contribute to neurodegeneration by altering cellular ATP level in a Drosophila IBMPFD model. PLoS Genet. 2011;7:e1001288 pubmed publisher
    ..Taken together, our analyses have defined the nature of IBMPFD-causing VCP mutations and made an unexpected link between cellular ATP level and IBMPFD pathogenesis...
  66. Guinto J, Ritson G, Taylor J, Forman M. Valosin-containing protein and the pathogenesis of frontotemporal dementia associated with inclusion body myopathy. Acta Neuropathol. 2007;114:55-61 pubmed
    ..In this report, we review current literature on IBMPFD, focusing on the pathology of the disease and the biology of VCP with respect to IBMPFD...
  67. Morissette J, Laurin N, Brown J. Sequestosome 1: mutation frequencies, haplotypes, and phenotypes in familial Paget's disease of bone. J Bone Miner Res. 2006;21 Suppl 2:P38-44 pubmed
    ..The P392L mutation was the most prevalent, embedded in two different haplotypes, possibly shared by other populations. We also examined the phenotype and penetrance of P392L...
  68. Kottlors M, Moske Eick O, Huebner A, Krause S, Mueller K, Kress W, et al. Late-onset autosomal dominant limb girdle muscular dystrophy and Paget's disease of bone unlinked to the VCP gene locus. J Neurol Sci. 2010;291:79-85 pubmed publisher
    ..The family presented here suggests that a yet-unknown genetic defect can give rise to an autosomal dominant myopathy with Paget's disease but without dementia...
  69. Adami S, Bartolozzi P, Brandi M, Falchetti A, Filipponi P, Gonnelli S, et al. [Italian guidelines for the diagnosis and treatment of Paget's disease of bone]. Reumatismo. 2007;59:153-68 pubmed
    ..The document provides the most updated recommendations based primarily on the "evidence-based- medicine" but also on the Italian regulation for the diagnostic procedures and on the available medical treatments...
  70. Hooper M, Faustino A, Reid I, Hosking D, Gilchrist N, Selby P, et al. Randomized, active-controlled study of once-weekly alendronate 280 mg high dose oral buffered solution for treatment of Paget's disease. Osteoporos Int. 2009;20:141-50 pubmed publisher
    ..A once-weekly alendronate 280 mg oral buffered solution was compared with an alendronate 40 mg/day tablet. While both were similarly effective, the tablet appeared to be better tolerated in this study...
  71. Layfield R. The molecular pathogenesis of Paget disease of bone. Expert Rev Mol Med. 2007;9:1-13 pubmed
  72. Garner T, Long J, Layfield R, Searle M. Impact of p62/SQSTM1 UBA domain mutations linked to Paget's disease of bone on ubiquitin recognition. Biochemistry. 2011;50:4665-74 pubmed publisher
  73. Chamoux E, Couture J, Bisson M, Morissette J, Brown J, Roux S. The p62 P392L mutation linked to Paget's disease induces activation of human osteoclasts. Mol Endocrinol. 2009;23:1668-80 pubmed publisher
    ..Moreover, the most-commonly reported p62 mutation, P392L, certainly contributes to the overactive state of osteoclasts in PDB...
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    ..We highlight areas that require further study, particularly in light of the pharmacological interest in targeting the RANK signalling pathway to treat diseases caused by excessive bone resorption...
  75. Whyte M. Paget's disease of bone and genetic disorders of RANKL/OPG/RANK/NF-kappaB signaling. Ann N Y Acad Sci. 2006;1068:143-64 pubmed
    ..Biochemical markers indicate rapid skeletal remodeling. In FEO, osteolysis progresses to fat-filled bone rather than to osteosclerosis. Antiresorptive therapy with bisphosphonates can be effective for each disorder...
  76. Roodman G. Insights into the pathogenesis of Paget's disease. Ann N Y Acad Sci. 2010;1192:176-80 pubmed publisher
    ..These studies suggest that both genetic and environmental factors contribute to PD...