{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T21:12:02Z","timestamp":1791925922359,"version":"4.3.4"},"reference-count":58,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2000,12,1]],"date-time":"2000-12-01T00:00:00Z","timestamp":975628800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2000,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Paget's disease of bone is a common bone disease characterized by increased and disorganized bone remodeling at focal sites throughout the skeleton. The etiology of the disease is unresolved. A persistent viral infection has long been suggested to cause the disease. Antigen and\/or nucleic acid sequences of paramyxoviruses (in particular measles virus [MV], canine distemper virus [CDV], and respiratory syncytial virus [RSV]) have been reported in pagetic bone by a number of groups; however, others have been unable to confirm this and so far no virus has been isolated from patients. Here, we reexamined the question of viral involvement in Paget's disease in a study involving 53 patients with established disease recruited from seven centers throughout the United Kingdom. Thirty-seven patients showed clear signs of active disease by bone scan and\/or histological assessment of the bone biopsy specimens and 12 of these had not received any therapy before samples were taken. Presence of paramyxovirus nucleic acid sequences was sought in bone biopsy specimens, bone marrow, or peripheral blood mononuclear cells using reverse-transcription polymerase chain reaction (RT-PCR) with a total of 18 primer sets (7 of which were nested), including 10 primer sets (including 3 nested sets) specifically for MV or CDV. For each patient at least one sample was tested with all primer sets by RT-PCR and no evidence for the presence of paramyxovirus RNA was found in any patient. In 6 patients, bone biopsy specimens with clear histological evidence of active disease tested negative for presence of measles and CDV using immunocytochemistry (ICC) and in situ hybridization (ISH). Intranuclear inclusion bodies, similar to those described by others previously, were seen in pagetic osteoclasts. The pagetic inclusions were straight, smooth tubular structures packed tightly in parallel bundles and differed from nuclear inclusions, known to represent MV nucleocapsids, in a patient with subacute sclerosing panencephalitis (SSPE) in which undulating, diffuse structures were found, arranged loosely in a nonparallel fashion. In the absence of amplification of viral sequences from tissues that contain frequent nuclear inclusions and given that identical inclusions are found in other bone diseases with a proven genetic, rather than environmental, etiology, it is doubtful whether the inclusions in pagetic osteoclasts indeed represent viral nucleocapsids. Our findings in this large group of patients recruited from throughout the United Kingdom do not support a role for paramyxovirus in the etiology of Paget's disease.<\/jats:p>","DOI":"10.1359\/jbmr.2000.15.12.2315","type":"journal-article","created":{"date-parts":[[2006,4,27]],"date-time":"2006-04-27T02:33:34Z","timestamp":1146105214000},"page":"2315-2329","source":"Crossref","is-referenced-by-count":124,"title":["A Negative Search for a Paramyxoviral Etiology of Paget's Disease of Bone: Molecular, Immunological, and Ultrastructural Studies in U.K. Patients"],"prefix":"10.1093","volume":"15","author":[{"given":"M. H.","family":"Helfrich","sequence":"first","affiliation":[{"name":"Department of Medicine and Therapeutics, University of Aberdeen, Aberdeen, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. P.","family":"Hobson","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, University of Aberdeen, Aberdeen, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P. S.","family":"Grabowski","sequence":"additional","affiliation":[{"name":"Present address: Department of Pediatrics, University of Sheffield, Sheffield, United Kingdom"},{"name":"Department of Medicine and Therapeutics, University of Aberdeen, Aberdeen, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Zurbriggen","sequence":"additional","affiliation":[{"name":"Institute of Animal Neurology, University of Berne, Berne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. L.","family":"Cosby","sequence":"additional","affiliation":[{"name":"School of Biology and Biochemistry, Queens University, Belfast, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G. R.","family":"Dickson","sequence":"additional","affiliation":[{"name":"School of Medicine and Health Sciences, Queens University, Belfast, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W. D.","family":"Fraser","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry, Royal Liverpool University Hospital, Liverpool, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. G.","family":"Ooi","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry, Royal Liverpool University Hospital, Liverpool, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P. L.","family":"Selby","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Manchester, Manchester, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. J.","family":"Crisp","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Addenbrooke's Hospital, Cambridge, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. G. H.","family":"Wallace","sequence":"additional","affiliation":[{"name":"Withers Orthopedic Unit, Musgrave Park Hospital, Belfast, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Kahn","sequence":"additional","affiliation":[{"name":"Department of Human Metabolism, University of Sheffield Medical School, Sheffield, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. H.","family":"Ralston","sequence":"additional","affiliation":[{"name":"Department of Medicine and Therapeutics, University of Aberdeen, Aberdeen, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2009,12,2]]},"reference":[{"key":"2024020714082113400_bib1","volume-title":"Pathophysiology and Treatment of Paget's Disease of Bone","author":"Kanis","year":"1992","edition":"1st Ed."},{"key":"2024020714082113400_bib2","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1093\/oxfordjournals.bmb.a072011","article-title":"The epidemiology of Paget's disease of bone","volume":"40","author":"Barker","year":"1984","journal-title":"Br Med Bull"},{"key":"2024020714082113400_bib3","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1359\/jbmr.1999.14.2.192","article-title":"The epidemiology of Paget's disease in Britain: Is the prevalence decreasing?","volume":"14","author":"Cooper","year":"1999","journal-title":"J Bone Miner Res"},{"key":"2024020714082113400_bib4","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.1136\/bmj.280.6222.1105","article-title":"Paget's disease of bone: The Lancashire focus","volume":"280","author":"Barker","year":"1980","journal-title":"BMJ"},{"key":"2024020714082113400_bib5","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1002\/jbmr.5650100421","article-title":"Frequency and characteristics of familial aggregation of Paget's disease of bone","volume":"10","author":"Morales-Piga","year":"1995","journal-title":"J Bone Miner Res"},{"key":"2024020714082113400_bib6","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1359\/jbmr.1998.13.6.911","article-title":"Paget's disease of bone: Evidence for a susceptibility locus on chromosome 18q and for genetic heterogeneity","volume":"13","author":"Haslam","year":"1998","journal-title":"J Bone Miner Res"},{"key":"2024020714082113400_bib7","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1016\/S8756-3282(00)00278-7","article-title":"Familial Paget's disease of bone: Patterns of inheritance and frequency of linkage to chromosome 18q","volume":"26","author":"Hocking","year":"2000","journal-title":"Bone"},{"key":"2024020714082113400_bib8","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1038\/71667","article-title":"Mutations in TNFRSF11A, affecting the signal peptide of RANK, cause familial expansile osteolysis","volume":"24","author":"Hughes","year":"2000","journal-title":"Nat Genet"},{"key":"2024020714082113400_bib9","doi-asserted-by":"crossref","first-page":"7S","DOI":"10.1016\/S8756-3282(99)00024-1","article-title":"Paget's disease in New Zealand: Is it changing?","volume":"24","author":"Cundy","year":"1999","journal-title":"Bone"},{"key":"2024020714082113400_bib10","doi-asserted-by":"crossref","first-page":"1104","DOI":"10.1002\/art.1780231006","article-title":"Bone tissue in Paget's disease of bone. 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