Mineral density of trabecular bone at the metaphyses of right tibiae was measured by peripheral quantitative computed tomography (pQCT) in ovariectomized rats. Bone mineral density (BMD) decreased dramatically in the 4 weeks following
ovariectomy, suggesting that the method is sensitive enough to detect decreased bone mineral density within a short period. Orally administered
incadronate dose dependently inhibited the decrease in trabecular bone
mineral density induced by
ovariectomy, as assessed 4 weeks after surgery. Significant inhibition was observed at doses of more than 0.3 mg/kg/day. Moreover,
incadronate at doses of 1 mg/kg or more inhibited the increase in urinary
deoxypyridinoline levels induced by
ovariectomy, and although slightly increased serum intact
parathyroid hormone (PTH) levels were observed, no significant alteration in serum
calcium ion levels or urinary
calcium excretion occurred. In contrast, while
alfacalcidol inhibited the decrease in bone mineral density and the increase in urinary
deoxypyridinoline levels at a dose of 300 ng/kg, it significantly lowered serum intact PTH levels and elevated serum free
calcium levels as well as urinary
calcium excretion. These results suggest that
incadronate exerts its pharmacological effect (inhibition of
bone resorption and increase in bone mass) by a mechanism different from that of alfacacidol.