PRECLINICAL PHARMACOLOGY OF ALENDRONATE

This brief review summarizes some of the preclinical findings of studi es aimed at assessing the efficacy and safety of the aminobisphosphona te alendronate (ALN) in preventing or restoring the bone loss caused b y calcium or estrogen deficiency. Mode of action studies show that ALN localizes at sites of bone resorption and inhibits osteoclastic activ ity. In secondary hyperparathyroidism caused by calcium-deficient diet s in the rat, ALN reduced the bone loss. For low doses, daily administ ration proved most efficient. In ovariectomized rats, ALN both prevent ed and reversed the bone changes produced by estrogen deficiency at or al doses equivalent to 0.1 mg/kg per day or higher, and also maintaine d the mechanical strength of vertebrae. In ovariectomized baboons, whi ch show bone changes similar to those seen in ovariectomized women, AL N also prevented the increase in bone turnover and increased both bone volume and bone strength in vertebrae. In a comparative study between ALN and etidronate, we found that ALN was 1000-fold more potent in in hibiting bone resorption and had at least a 1000-fold higher safety ma rgin with respect to inhibition of mineralization and osteomalacia.