Osteoclast kinetics in osteopetrotic (ia) rats cured by spleen cell transfers from normal littermates

Excessive skeletal mass and reduced bone resorption characteristic of osteopetrosis in young ia rats can be corrected by irradiation and transfer of spleen cells from normal littermates. Cell population analyses and 3H-thymidine (3H-TdR) autoradiographic methods were used to determine osteoclast population dynamics and kinetics of incorporation of nuclei following whole-body irradiation and spleen cell transfer in ia/ia rats and in untreated ia rats and their (ia/+) normal littermates. The numbers of osteoclasts per metaphyseal area were greater in ia rats than in (ia/+) normal littermates. Untreated ia rats had greater rates of incorporation of 3H-TdR-labeled nuclei into osteoclasts but were reduced to near normal values following irradiation and spleen cell transfer. Labeled osteoclast nuclei were first seen in the primary spongiosa of the femoral metaphysis and with increasing time appeared at greater distances from the epiphyseal growth plate as the bones grew In length. These sites of osteoclast neogenesis correspond to sites where restoration of bone resorption is initially seen following bone marrow and splenic transplants in the treatment of osteopetrosis.