Role of carbonic anhydrase in bone: partial inhibition of disuse atrophy of bone by parenteral acetazolamide

Carbonic anhydrase inhibitor acetazolamide blocks the hypercalcemic response to parathyroid hormone (PTH) and to dibutyryl 3',5'-cyclic AMP in the nephrectomized-parathyroidectomized rat. In addition, we have reported that acetazolamide, when incorporated in the diet, partially prevents denervation-induced bone loss in a rat model of disuse osteoporosis. The present study compares the effectiveness of orally and subcutaneously administered acetazolamide in preventing denervation-induced bone loss in the rat model. The rats were treated with acetazolamide either orally, by incorporation in the diet of concentrations of 0.2, 0.5, or 1.5% for 15 days, or parenterally by two different subcutaneous methods of administration. The latter included either injection twice daily for 15 days or continuous infusion for 8 days using an osmotic minipump. It was found that parenteral administration was as effective in partially preventing denervation-induced bone mass changes as oral administration. In addition, protection by the parenteral route could be accomplished with much smaller daily doses; continuous infusion required the least daily dose. Approximately 50% protection was observed to occur with daily doses of 1,094, 129, and 8 mg/kg body weight for the oral, subcutaneous injection, and subcutaneous infusion routes respectively. These findings are consistent with our concept that carbonic anhydrase plays a significant role in bone metabolism.