A negative search for a paramyxoviral etiology of Paget's disease of bone:Molecular, immunological, and ultrastructural studies in UK patients

Paget's disease of bone is a common bone disease characterized by increased and disorganized bone remodeling at focal sites throughout the skeleton. T he etiology of the disease is unresolved, A persistent viral infection has long been suggested to cause the disease. Antigen and/or nucleic acid seque nces 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 con firm this and so far no virus has been isolated from patients. Here, we ree xamined the question of viral involvement in Paget's disease in a study inv olving 53 patients with established disease recruited from seven centers th roughout the United Kingdom. Thirty-seven patients showed clear signs of ac tive 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 1 8 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 s ample was tested with all primer sets by RT-PCR and no evidence for the pre sence of paramyxovirus RNA was found in any patient. In 6 patients, bone bi opsy specimens with clear histological evidence of active disease tested ne gative for presence of measles and CDV using immunocytochemistry (ICC) and in situ hybridization (ISH), Intranuclear inclusion bodies, similar to thos e described by others previously, were seen in pagetic osteoclasts, The pag etic inclusions were straight, smooth tubular structures packed tightly in parallel bundles and differed from nuclear inclusions, known to represent M V nucleocapsids, in a patient with subacute sclerosing panencephalitis (SSP E) in which undulating, diffuse structures were found, arranged loosely in a nonparallel fashion. In the absence of amplification of viral sequences f rom tissues that contain frequent nuclear inclusions and given that identic al inclusions are found in other bone diseases with a proven genetic, rathe r than environmental, etiology, it is doubtful whether the inclusions in pa getic osteoclasts indeed represent viral nucleocapsids. Our findings in thi s large group of patients recruited from throughout the United Kingdom do n ot support a role for paramyxovirus in the etiology of Paget's disease.