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Abstract
Bisphosphonates (BP) are pyrophosphate analogs, P-C-P with various carbon side-chains. The phosphate groups are responsible for the low gastrointestinal absorption (about 1%), limited penetration into cells, adsorption to bone mineral and rapid excretion in the urine. Based on the C side-chains, BPs can inhibit osteoclastic bone resorption with potencies which differ by as much as 10,000-fold among compounds. The most potent inhibitors are aminobisphosphonates. Studies of the amino-BP alendronate show preferential uptake at sites of bone resorption where they block osteoclastic activity by inhibiting ruffled border formation. BPs are the treatment of choice for hypercalcaemia of malignancy, where a single infusion with a potent BP will normalize serum calcium in 80% of the patients. Paget's disease also shows an excellent long-term response to BPs. In addition, BPs are being studied for the treatment of osteoporosis and other bone disorders which could be helped by inhibition of bone resorption.
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