A quantitative histologic study of avian osteopetrotic bone demonstrating normal osteoclast numbers and increased osteoblastic activity.

Hyperostotic diseases caused by increased osteoblastic activity are poorly understood partially because a suitable animal model is not available for their study. In contrast, a hyperostotic disorder caused by defective osteoclasts (mammalian osteopetrosis) is better understood, largely because of advances made with a murine model of the disease. The avian form of osteopetrosis is caused by RNA tumor viruses, but the role of osteoblasts and osteoclasts is not clear. We have performed a morphometric analysis of osteopetrotic avian bone to provide basic information about changes in the cells of bones from animals developing the disease. Chick embryos were injected at 12 days of incubation with a virus (MAV-2(0)) that induces osteopetrosis at a high frequency. Changes in bone volume were detected 14 days after virus injection. By 3 weeks of age, the bone volumes of osteopetrotic chicks were 4.7-fold larger than controls. The mean caliper diameter of an osteoclast was the same in osteopetrotic and normal bone. The number of osteoclasts per tibia increased in osteopetrotic animals, but the density of osteoclasts decreased. The presence of an increased number of osteoclasts of a normal size rules out the possibility that the virus causes osteopetrosis by selectively killing osteoclasts. The total bone-nonbone interface increased in osteopetrosis, and greater than 90 per cent of interface surface was devoted to bone deposition. These results indicate that avian osteopetrosis is an osteoblastic, proliferative disorder of bone and may serve as an excellent animal model for human diseases in which osteoblasts increase in number.