Morphological evidence of reduced bone resorption in osteopetrotic (op) mice

Osteopetrosis, a metabolic bone disease in which a generalized accumulation of bone mass reduces or obliterates marrow cavities, is inherited as an autosomal recessive in several mammalian species. A recently discovered mutation in mice, the osteopetrosic (op) mutation, exhibits an elevation in bone matrix synthesis and a resistance to the hypercalcemic effects of exogenous parathyroid extract when young mutants are compared with normal littermates. This investigation examined the number, cytology, and ultrastructure of osteoclasts and the structure of bone surfaces in op mice in a morphologic assessment of bone resorption. Compared with normal littermates, op mice have a severe deficiency of osteoclasts, which also contain unusual toluidine blue-positive and electron-dense cytoplasmic inclusions and hypertrophy of clear zones and ruffled borders. Marrow spaces in op mice contained large numbers of megakaryocytes and large lipoid masses. Bone surfaces exhibiting evidence of resorption by scanning electron microscopy in normal littermates showed no evidence of resorption in op mice. Instead, these areas were characterized by morphologic features of bone formation. These data offer morphologic evidence of a reduction of bone resorption in this mutation. They are interpreted to mean 1) that op mice have a severe reduction in numbers or proliferative capacity of osteoclast precursors, which may be related to the cellular inclusions in the osteoclast population, and 2) that hypertrophy of the ruffled borders and clear zones of op osteoclasts is a compensatory attempt to increase bone resorption.