Osteopetrosis, a skeletal condition characterized by excessive accumulation of bone, is an inherited disease in man, rats and mice. In ia rats the condition undergoes spontaneous permanent remission beginning 30 to 50 days after birth, in contrast to the disease in mice and men. Thus, the ia rat offers a unique opportunity to analyze factors suspected of causing the skeletal condition.

In the present investigation bone formation and bone resorption have been measured at various ages in ia rats and normal littermates. Bone matrix formation, measured by ³H‐proline uptake, was decreased slightly during the first three postnatal weeks and elevated slightly thereafter. Bone resorption, stimulated by injection of parathyroid extract, was determined in vivo as the rate of release of ³H from bone after incorporation of ³H‐proline. Bone resorption was reduced 20% at two weeks and elevated 20% by three weeks. Administration of parathyroid extract or thyroxine, or a deficiency of thyrocalcitonin produced by thyroidectomy (supplemented with thyroxine), did not hasten remission. An abnormally high cytoplasmic concentration of acid phosphatase activity was observed in ia osteoclasts during the first two weeks. The skeletal signs of spontaneous remission, appearing between 30 and 50 days after birth, were preceded by a normal response of the serum calcium to exogenous parathyroid extract, by increased bone resorption and by a more normal cytoplasmic distribution of acid phosphatase activity during the third postnatal week.

These observations are interpreted to indicate that the osteopetrotic condition of ia rats is not due to deficiencies of parathyroid hormone or thyroxine or an excess of thyrocalcitonin but results from failure of osteoclasts to respond to stimuli promoting resorption. Specifically, these cells seem able to synthesize but not release normal amounts of the lysosomal enzyme acid phosphatase.