Plasma cyclic AMP response to calcitonin: a potential clinical marker of bone turnover

A noninvasive marker of bone turnover would be useful in predicting which patients are at risk of rapid bone loss and in monitoring response to therapy. Calcitonin (CT)-induced hypocalcemia correlates with bone turnover but has not been a clinically useful test because changes in serum calcium are small, and test duration is long. CT rapidly increases plasma cAMP levels. We conducted studies in rats and in man to characterize the origin of this rise, and to determine its suitability as a potential clinical marker of bone resorption. Administration of CT to rats resulted in a prompt and sustained rise in plasma cAMP. This effect was not blunted by nephrectomy and was greater in calcium-deprived rats with increased bone resorption. Thus, it appears to reflect CT action on bone. An intramuscular injection of 100 units salmon CT elevated plasma cAMP in 18 normal men and women. This effect was observed by 20 min after injection and persisted over 2 h. Although basal levels of plasma cAMP were similar in healthy postmenopausal women and men, the response to CT was greater in women. The response of women with hyperparathyroidism was greater than that of normal women, and the response of pagetic men was greater than that of normal men. The rise in plasma cAMP following CT is rapid and easily measured and appears to correlate with the state of bone remodeling. Additional studies will be required in osteoporotic subjects with high and low remodeling activity before the clinical utility of this test can be determined.