Figure 1.

(a) Chemical structures of bisphosphonates. Nitrogen-containing bisphosphonates such as zoledronate and ibandronate have a hydroxyl group in the R ¹ position and nitrogen-containing R ² side chains. (b) Farnesyl pyrophosphate synthase-catalyzed condensation reactions. Isopentenyl diphosphate (IPP) first reacts with dimethylallyl diphosphate (DMAPP) to form geranyl diphosphate (GPP), releasing pyrophosphate (PP_i). GPP then reacts with IPP to form farnesyl pyrophosphate (FPP) and free PP_i.