[Pharmacological and clinical properties of alendronate sodium hydrate].
Alendronate (alendronate sodium hydrate; Bonalon Tablet, 5 mg) is a nitrogen-containing bisphosphonate, which combines with the bone surface and reduces osteoclast-mediated bone resorption. It is a third-generation bisphosphonate compound, specifically distributed on the surface of bone resorption and taken into osteoclasts. Under the closed circumstances which is formed with osteoclast and the bone surface, alendronate becomes detached from the bone surface and taken into osteoclast since acid released from osteoclast leads to pH decrease (acidified). The uptaken alendronate blocks the pathway of mevalonic acid synthesis, which is cholesteric synthesis, inhibits the prenylation of GTP binding protein, and decreases the osteoclast's function by influencing the cytoskeleton. This restraint of alendronate in bone resorption against osteoclasts is reversible, showing no cytotoxicity at more than hundredfold concentration level at which action occurs. Alendronate is an agent for the treatment of osteoporosis that has established safety with regards to bone quality since it neither inhibits bone calcification nor influences fracture healing in chronic administration. The most serious morbidity in osteoporosis is developing fractures. The efficacy of alendronate on restraining fracture, as well as on increase in BMD, is evidenced in Japan. Recently, in addition to senile or postmenopausal osteoporosis, drug-induced osteoporosis, such as steroid-induced osteoporosis, has attracted attention. In this regard, alendronate has been found to be an effective agent for the treatment of osteoporosis overseas, being approved in over 90 countries and used by more than 4.5 million patients. This review will give an outline of alendronate, the preparation to have introduced a concept of Evidence Based Medicine earlier, from pharmacodynamic action to clinical efficacy.
Ohta
Tomohiro
T
Department, Medical & Pharmaceutical Group, Teijin Ltd. 1-1, Uchisaiwai-Cho 2-Chome, Chiyoda-Ku, Tokyo 100-8585, Japan. to.oota@teijin.co.jp
Komatsu
Shozo
S
Tokutake
Noboru
N
D019386:Alendronate / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use*; D000818:Animals; D015519:Bone Density; D001862:Bone Resorption; D002986:Clinical Trials as Topic; D003864:Depression, Chemical; D050723:Fractures, Bone / Q000517:prevention & control; D019204:GTP-Binding Proteins / Q000378:metabolism; D006801:Humans; D008798:Mevalonic Acid / Q000378:metabolism; D010010:Osteoclasts / Q000187:drug effects / Q000378:metabolism; D010024:Osteoporosis / Q000188:drug therapy* / Q000378:metabolism; D017368:Protein Prenylation / Q000187:drug effects
D019204:GTP-Binding Proteins; D008798:Mevalonic Acid; D019386:Alendronate