Bone tissue in paget's disease of bone ultrastructure and immunocytology

Abstract

Ultrastructural observations in Paget's disease of bone clarify aspects of bone cells in bone tissue and demonstrate the presence of specific intranuclear inclusions composed of microcylinders in the osteoclasts. The morphologic analysis of these structures suggests an analogy with virus material of the measles group. Results obtained using indirect immunofluorescence and immunoperoxidase techniques lend further support to the hypothesis of a viral etiology in Paget's disease of bone.

Measles Virus RNA Detected in Paget's Disease Bone Tissue by in situ Hybridization

“…In 80 to 9 0~ of these multinucleated cells, hybridization reactions were observed both in the cytoplasm, with a diffuse distribution, and in some of the numerous nuclei, with different levels of intensity. Autoradiographic grains were sometimes concentrated and localized over the nuclear area, in particular over clear nuclear inclusions which very probably correspond to the nuclear accumulation of specific microcytinders as previously described in Pagetic osteoclasts (Gherardi et al, 1980;Harvey et al, 1982;Mills & Singer, 1976;Rebel et al, 1980bRebel et al, , 1974.…”

“…Ultrastructural studies have shown the presence of specific inclusions in the enormous, multinucleated osteoclasts from Pagetic bone tissue. Morphological analyses have demonstrated that the structure, the dimensions and the cytoplasmic and nuclear distribution of the microcylindrical inclusions observed in Pagetic osteoclasts are very similar to the nucleocapsids found in cells infected with paramyxoviruses (Gherardi et al, 1980;Harvey et al, 1982;Howatson & Fornasier, 1982;Mills & Singer, 1976;Rebel et al, 1980bRebel et al, , 1974. Furthermore, using immunocytological techniques with polyclonal antibodies, several studies have demonstrated that osteoclasts from bone tissue in Paget's disease contain antigenic material related to measles virus and to respiratory syncytial virus, both of which are members of the family Paramyxoviridae (Basl6 et al, 1979;Mills et al, 1982;Rebel et al, 1980a;Singer & Mills, 1983).…”

“…These findings are consistent with the ultrastructural and immunocytological observations previously described. Electron microscopical studies have shown that the cytoplasm and nuclei of osteoclasts from Paget's bone tissue contain microcylindrical inclusions very similar to measles virus nucleocapsids (Gherardi et al, 1980;Harvey et al, 1982;Howatson & Fornasier, 1982;Rebel et al, 1980b). Immunological experiments have also demonstrated the presence of measles nucleocapsid protein antigens both in cytoplasm and in nuclei of Pagetic osteoclasts (Basl6 et al, 1979(Basl6 et al, , 1985Rebel et al, 1980a).…”

Cementless total hip arthroplasty in Paget’s disease of bone: a retrospective review

“…Paget's disease of bone (PDB) is a localised chronic osteopathy characterised by an osteoclastic dysfunction with increased resorption and subsequent compensatory formation of new woven bone with an anarchic microstructure [28]. This structural change produces bone that is expanded in size, more vascular and may lead to osseous deformities, structural weakness and altered joint biomechanics [29].…”

Genetic aspects of the Paget’s disease of bone: concerns on the introduction of DNA‐based tests in the clinical practice. Advantages and disadvantages of its application

“…Several authors have suggested that paramyxoviral infection may reproduce some features of PDB and the following findings have been considered to sustain a viral hypothesis in the PDB pathogenesis: (i) paramyxoviral-like nuclear inclusions have been commonly found in pagetic osteoclasts [24,25]; (ii) mRNAs or proteins from measles, canine distemper and respiratory syncytial viruses have been detected in samples from patients with PDB [26][27][28][29][30][31], but not in controls; (iii) infection with paramyxoviruses enables the occurrence of Paget-like changes in osteoclasts. Unfortunately, many other reports have not replicated similar findings in their analysed series [32][33][34][35].…”