Bisphosphonates: an overview with special reference to alendronate

Bisphosphonates, analogues of pyrophosphate, are potent inhibitors of osteo clast-mediated bone resorption. They are used in the treatment of Paget's d isease of bone, hypercalcaemia and osteolytic bone disease of malignancy, p rimary and secondary hyperparathyroidism, and in osteoporosis. Bisphosphona te treatment causes an early reduction in bone resorption followed by I lat er reduction in bone formation. The early inhibition of bone resorption ind uces I reduction in serum calcium which leads to increased parathyroid horm one (PTH). Ind subsequently Lin increase in 1,25-dihydroxyvitamin D. The se condary hyperparathyroidism of bisphosphonate treatment also leads to urina ry calcium conservation and phosphaturia, and a reduction in serum phosphat e. The increase in the PTH following bisphosphonate therapy is it response to the change in serum calcium and can occur even when there is hypercalcae mia, and this can cause confusion in the interpretation of PTH results. The hypocalcaemic response to bisphosphonates is occasionally severe, especial ly in patients with hypoparathyroidism. The recent elucidation of bisphosph onate action at the cellular level on the mevalonate pathway has led to int erest in its effects on lipoprotein metabolism, which may prove to be of cl inical significance. Newer and more potent bisphosphonates, are currently u ndergoing clinical trials in malignant bone disease and osteoporosis, and w ill lead to further advances in the optimal management of these conditions.