Delayed stimulatory effect of cyclic AMP on bone resorption in vitro

The effect of dibutyryl cyclic AMP (dbcAMP) and the phosphodiesterase inhibitors 3-isobutyl methylxanthine (IBMX) and theophylline on bone resorption was studied in an organ culture system for 96-114 h using half calvaria from 6-7 day old mice. The magnitude of resorption was assessed by measuring the release from the bones of previously incorporated 45Ca. It was observed that dbcAMP, IBMX and theophylline, following a lag period or a period of reduced bone resorption, all progressively increased mineral mobilization. Although the continuous presence of dbcAMP increased mineral mobilization more than a temporary exposure, a limited treatment of 24 h with the nucleotide was sufficient to bring about the delayed stimulatory response. It is concluded that the observations support our earlier proposal that cAMP is not a mediator of the early stages of parathyroid hormone (PTH)- and prostaglandin E2 (PGE2)-stimulated bone resorption. We suggest that the role played by cAMP may be related to the capacity of PTH and PGE2 to develop new osteoclasts, a phenomenon which takes more than 24 h to be observed.