Bone resorption in experimental otosclerosis in rats.

Localized bone resorption in the otic capsules of experimental rats was induced by immunization with type II collagen. The otospongiosis-like lesion showed enlarged vascular spaces that contained many fibroblasts and macrophages as well as occasional osteoclasts. A high level of acid phosphatase activity in the sera of immunized rats suggested that this enzyme is one of the important factors causing decalcification of the bony otic capsule, the first step of bone resorption. Immunofluorescent assay showed that collagenase and cyclooxygenase (prostaglandin synthetase) appeared within macrophages, fibroblasts, and osteoclasts in the bone resorption areas. These findings suggest that the collagenase and prostaglandin synthetase being produced by macrophages, fibroblasts, and osteoclasts are also involved in the processes of bone resorption in otospongiosis. Immunolocalization assay showed deposition of immunoglobulin and fibronectin on the bone matrix and vascular wall within the otospongiotic lesions. Chemotaxis studies showed that both anti-type II collagen serum and fibronectin might play a role as chemoattractants to recruit macrophages and fibroblasts to the bone resorption sites. In vitro studies also showed anti-type II collagen serum stimulates the fusion of macrophages to become multinucleated osteoclast-like cells. The antiserum also activate these cells to produce collagenase and prostaglandin synthetase. It is concluded that the chemotactic processes of macrophages and fibroblasts, the multinucleation of macrophages, and the activation of these cells may be basic processes causing bone resorption in otosclerosis. When sodium fluoride, an inhibitor of hydrolytic and proteolytic enzymes, was given to rats immunized with type II collagen, no obvious inhibition of bone resorption was seen in histologic sections.