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Proposed mechanism of bisphosphonate (BP) action. BPs inhibit a key step in the hydroxymethylglutaryl conenzyme A (HMG-CoA) reductase pathway through the inhibition of farnesyl-pyrophosphate synthase. Inhibition of protein isoprenylation results in osteoclast apoptosis and inhibition of osteoclast-mediated bone resorption. GTP, guanosine 5′ -triphosphate; PP, pyrophosphate; BMP-2, bone morphogenetic protein–2.
