Bisphosphonate mechanism of action

Abstract

The nitrogen-containing bisphosphonates (N-BPs), alendronate and risedronate, are the only pharmacologic agents shown to prevent spine and nonvertebral fractures associated with postmenopausal and glucocorticoid-induced osteoporosis. At the tissue level, this is achieved through osteoclast inhibition, which leads to reduced bone turnover, increased bone mass, and improved mineralization. The molecular targets of bisphosphonates (BPs) have recently been identified. This review will discuss the mechanism of action of BPs, focusing on alendronate and risedronate, which are the two agents most widely studied. They act on the cholesterol biosynthesis pathway enzyme, farnesyl diphosphate synthase. By inhibiting this enzyme in the osteoclast, they interfere with geranylgeranylation (attachment of the lipid to regulatory proteins), which causes osteoclast inactivation. This mechanism is responsible for N-BP suppression of osteoclastic bone resorption and reduction of bone turnover, which leads to fracture prevention.

Vascular calcification and osteolysis in diabetic neuropathy?is RANK-L the missing link?

“…Its dependence on increased blood flow explains why the process responds to rest (which will help to reduce it) and, possibly, to bisphosphonates [37,38]. Bisphosphonates inhibit the action of osteoclasts, although not by impacting directly on the OPG/RANK-L system [39,40], but their use also reduces local blood flow in other conditions associated with regional hyperaemia [41,42]. If the long-term benefit of bisphosphonates is ever proven in the Charcot foot, it is as likely to be the result of this effect on local circulation as on their inhibition of bone resorption by osteoclasts.…”

Osteoporosis and Periodontal Disease: Association and Mechanisms: An in-Depth Review

“…This effect was noted early in therapy. [28][29][30][31] However, the occurrence of osteonecrosis of the jaws with the use of intravenous bisphosphonates is of concern to the dental community. After initial observations by Wang at the University of California,osteonecrosis of the jaws is seen to occur more commonly in the mandible but has also been reported in the maxilla, and appears to be highly associated with periodontitis, other oral infections, and extraction of the affected teeth in majority of the reported cases.…”

O alendronato de sódio na prevenção da osteopenia secundária à imobilização gessada, em ratas: avaliação histomorfométrica

“…Assim, os bisfosfonatos são um grupo de drogas potentes que atuam na inibição da atividade osteoclás-tica, onde quer que ela seja necessária (33) . Isto explica a variedade de suas indicações.…”