A number of clinical and experimental studies suggest that the effects of calcium channel blockers are not limited to the cardiovascular system but might also involve skeletal calcium metabolism due to the presence of L-type calcium channels in osteoblastic cells. We therefore investigated the influence of calcium channel blockers of the dihydropyridine type (nifedipine, amlodipine) as well as of the phenylalkylamine type (verapamil, gallopamil) on basal and parathyroid hormone-induced bone resorption utilizing organ-cultured neonatal mouse calvaria. Only at M, amlodipine, verapamil and gallopamil reduced basal and parathyroid hormone-induced resorption In contrast, nifedipine, between M, exhibited a dose-dependent inhibitory effect on parathyroid hormone-related bone resorption by up to 50%. When calvariae were cultured for 48 hr in the presence of inhibitory concentrations of the calcium channel blockers and then stimulated with parathyroid hormone, only parietal bones pretreated with nifedipine remained completely responsive to the bone resorbing action of the hormone.For more than two decades calcium channel blockers have been extensively and successfully used for treatment of cardiovascular disorders such as hypertension, angina, or cardiac arrhythmias (Snyder & Reynolds 1985). Typically, calcium channel blockers are prescribed to patients in their middle age or later, i.e., at a life time with increasing incidence of osteoporosis. The question was raised therefore whether calcium channel blockers, as many other drugs, could have adverse effects on bone metabolism and thereby possibly contribute to deterioration of bone mass in advanced age. Although experimental studies suggest that calcium channel blockers through modulation of osteoblast function could interfere with bone remodeling (Guggino et al. 1989), in vivo investigations in experimental animals and humans on that issue have yielded only conflicting results. In growing rabbits nifedipine lowers cancellous bone volume, mineral apposition rate and growth plate thickness (Duriez ef al. 1993). In line with these findings chronic treatment with verapamil in female rats induces osteopenia, whereas in male rats bone growth was inhibited (Samnegard & Sjadtn 1992). Boesgard et al. (1991) reported that prolonged treatment with clinical doses of verapamil did not affect indices of calcium and bone metabolism in humans. Also, chronic nifedipine use seems not to be associated with either beneficial or adverse effects on bone metabolism in males (Albers et al. 1991). In contrast, SjiSden et al. (1990) in patients with postsurgical hypoparathyroidism, verapamil increased serum calcium and phosphate levels without changing intestinal absorption or urinary excretion of calcium. This suggests that verapamil affects bone mineral metabolism .Calcium channel blockers exert multiple effects on osteoblasts. Verapamil for instance inhibits DNA synthesis in mouse calvarial MC3T3-El cells (Kim et al. 1991), and suppresses basal and 1,2S-dihydroxyvitamin D3-sti...