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.
D000086:Acetazolamide / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001284:Atrophy / Q000209:etiology; D001835:Body Weight / Q000187:drug effects; D001847:Bone Diseases / Q000473:pathology* / Q000517:prevention & control; D002118:Calcium / Q000097:blood; D002256:Carbonic Anhydrases / Q000502:physiology*; D003714:Denervation; D004032:Diet; D007263:Infusions, Parenteral; D007279:Injections, Subcutaneous; D008297:Male; D010710:Phosphates / Q000097:blood; D051381:Rats; D011919:Rats, Inbred Strains
D010710:Phosphates; D002256:Carbonic Anhydrases; D000086:Acetazolamide; D002118:Calcium