1995 年 105 巻 5 号 p. 285-294
Bisphosphonates have a P-C-P bond instead of the P-O-P bond of inorganic pyrophosphate that makes them resistant to enzymatic degradation and gives them a high affinity for hydroxyapatite. They are potent blockers of osteoclastic bone resorption and have been successfully used to treat metabolic bone diseases that involve increased bone resorption. It is possible to synthesize a variety of bisphosphonates by substituting the hydrogen on the carbon atom. The pharmacological characteristics and activity varies greatly from compound to compound, ranging from 1 to 10, 000. Some structure-activity relationships have been found, but no clear-cut one has been established yet. There is a general consensus that the inhibition of bone resorption by bisphosphonates is not caused by the inhibition of dissolution of the hydroxyapatite crystal, but is actually caused through a cellular mechanism that is not completely understood. In the present review article, the possible mode of bisphosphonate action was discussed with special reference to: (1) whether bisphosphonates inhibit the function of mature osteoclasts directly or through osteoblasts and (2) whether bisphosphonates inhibit the proliferation or differentiation of osteoclast progenitors to osteoclasts.