Nitrogenous Bisphosphonate

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hmg-coa reductase pathway


disruption of hmg coa-reductase pathway @ level of fpps prevents formation of 2 metabolites (farnesol , geranylgeraniol) essential connecting small proteins cell membrane. phenomenon known prenylation, , important proper sub-cellular protein trafficking (see lipid-anchored protein principles of phenomenon).


while inhibition of protein prenylation may affect many proteins found in osteoclast, disruption lipid modification of ras, rho, rac proteins has been speculated underlie effects of bisphosphonates. these proteins can affect both osteoclastogenesis, cell survival, , cytoskeletal dynamics. in particular, cytoskeleton vital maintaining ruffled border required contact between resorbing osteoclast , bone surface.


statins class of drugs inhibit hmg-coa reductase pathway. unlike bisphosphonates, statins not bind bone surfaces high affinity, , not specific bone. nevertheless, studies have reported decreased rate of fracture (an indicator of osteoporosis) and/or increased bone mineral density in statin users. overall efficacy of statins in treatment of osteoporosis remains controversial.








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