Histological ultrastructural, and biochemical studies of the tissues of a patient with osteopetrosis were done. The bone contained an increased number of osteoclasts which were characterized ultrastructurally by the absence of ruffled borders and clear zones, hallmarks of actively resorbing osteoclasts. In contrast with normal human bone, tissue collagenase was not detected in osteopetrotic bone cultured in vitro, nor was tissue collagenase activity released when the osteopetrotic bone was incubated with parathyroid hormone. No striking abnormalities of parathyroid hormone or calcitonin were found in the blood or parathyroid and thyroid glands. Except for a slight increase in the extent of lysine hydroxylation of bone collagen, no significant biochemical abnormality of collagen was found. The histological, ultrastructural, and biochemical data support the hypothesis that the basic defect in osteopetrosis is cellular and the osteoclasts, in particular, are abnormal. They appear to be unable to resorb bone and cartilage, and they do not appear to respond to parathyroid hormone in a completely normal way.
Clinical relevance: Bone marrow transplantation has produced improvement in both experimental animals and humans and should be actively considered in a child with osteopetrosis who is not thriving.