A negative search for a paramyxoviral etiology of Paget's disease of bone: molecular, immunological, and ultrastructural studies in UK patients
Autor: | Peter Grabowski, Peter Selby, Glenn R. Dickson, Stuart H. Ralston, Miep H. Helfrich, S. Kahn, C.G. Ooi, R.G.H. Wallace, William D. Fraser, A. Zurbriggen, S.L. Cosby, Richard P. Hobson, A.J. Crisp |
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Rok vydání: | 2000 |
Předmět: |
Male
Pathology medicine.medical_specialty Bone disease viruses Endocrinology Diabetes and Metabolism Biopsy Sensitivity and Specificity Subacute sclerosing panencephalitis Virus Bone and Bones Respirovirus Bone remodeling Medicine Humans Orthopedics and Sports Medicine Distemper Virus Canine In Situ Hybridization Aged DNA Primers Aged 80 and over business.industry Canine distemper Reverse Transcriptase Polymerase Chain Reaction Reproducibility of Results Middle Aged medicine.disease Osteitis Deformans Virology Immunohistochemistry United Kingdom Respiratory Syncytial Viruses Paget's disease of bone medicine.anatomical_structure Measles virus Case-Control Studies DNA Viral Female Bone marrow Viral disease business |
Zdroj: | Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 15(12) |
ISSN: | 0884-0431 |
Popis: | 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. |
Databáze: | OpenAIRE |
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