Cimetidine: Lack of direct effects on bone in vitro

Cimetidine, at concentrations in the range which would be obtained during normal therapeutic use, i.e. 1 μg/ml, had no significant effects on either control or stimulated ⁴⁵Ca release from fetal rat limb bones after 48 hours in culture. Renal excretion plays a significant role in the elimination of cimetidine and lower clearance, resulting in blood levels of 1.8-2.0 μg cimetidine/ml, has been observed in patients with uremia. Since the hypocalcemic effects may be more likely in such patients, the effects of higher cimetidine concentrations were tested on bone in vitro. No significant inhibition was observed at concentrations up to 10^-4M (25.6 μg/ml). Thus, the results suggest that the hypocalcemic effects of cimetidine are not mediated by inhibition of bone resorption and the absence of hypocalcemia in many patients in whom cimetidine lowered serum parathyroid hormone is not due to concomitant release of calcium from bone.