Bisphosphonates in the treatment of metabolic bone diseases.
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.
Rodan
G A
GA
Department of Bone Biology and Osteoporosis Research, Merck Sharp and Dohme Research Laboratories, West Point, PA 19486.
Balena
R
R
D019386:Alendronate; D000818:Animals; D001851:Bone Diseases, Metabolic / Q000188:drug therapy*; D001862:Bone Resorption / Q000188:drug therapy; D004164:Diphosphonates / Q000493:pharmacokinetics / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D006934:Hypercalcemia / Q000188:drug therapy; D008297:Male; D010001:Osteitis Deformans / Q000188:drug therapy; D010024:Osteoporosis / Q000188:drug therapy
D004164:Diphosphonates; D019386:Alendronate