Mechanism of action Bisphosphonate

non-nitrogenous

non-n-containing bisphosphonates:

etidronate (didronel) — 1 (potency relative of etidronate)
clodronate (bonefos, loron) — 10
tiludronate (skelid) — 10

the non-nitrogenous bisphosphonates (disphosphonates) metabolised in cell compounds replace terminal pyrophosphate moiety of atp, forming non-functional molecule competes adenosine triphosphate (atp) in cellular energy metabolism. osteoclast initiates apoptosis , dies, leading overall decrease in breakdown of bone. type of bisphosphonate has overall more negative effects nitrogen containing group, , prescribed far less often.

nitrogenous

n-containing bisphosphonates:

pamidronate (apd, aredia) — 100
neridronate (nerixia) — 100
olpadronate — 500
alendronate (fosamax) — 500
ibandronate (boniva) — 1000
risedronate (actonel) — 2000
zoledronate (zometa, aclasta) — 10000

nitrogenous bisphosphonates act on bone metabolism binding , blocking enzyme farnesyl diphosphate synthase (fpps) in hmg-coa reductase pathway (also known mevalonate pathway).

bisphosphonates contain isoprene chains @ r1 or r2 position can impart specificity inhibition of ggps1.

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.