Osteoclast populations in congenital osteopetrosis: additional evidence of heterogeneity.

Osteopetrosis is a metabolic bone disease characterized by excessive accumulation of skeletal mass due to a reduction in bone resorption. The pathogenesis of osteopetrosis is reduced osteoclast function. Reports of osteoclast numbers in several mammalian mutations exhibiting osteopetrosis have shown them to be increased, decreased, or normal in numbers. The present investigation quantitated the osteoclast populations and examined the cytology of osteoclasts by light microscopy in calvarial and tibial sites in one rabbit and two mouse mutations and compared them with their normal littermates. Our observations show that osteoclast numbers are, depending on the particular mutation, increased, decreased, or comparable to those found in normal littermates. In each mutation, however, osteoclasts fail to exhibit the cytoplasmic vacuolization next to bone surfaces seen in normal osteoclasts. These data provide additional evidence of heterogeneity in the congenital mammalian osteopetrosis and suggest that these mutations may be significant sources of new information about the biology of osteoclasts.