In vitro Comparison of Clodronate, Pamidronate and Zoledronic Acid Effects on Rat Osteoclasts and Human Stem Cell‐Derived Osteoblasts

Abstract

In the present study we compared the first generation non-nitrogen-containing bisphosphonate, clodronate with second and third generation nitrogen-containing bisphosphonates, pamidronate and zoledronic acid in dynamic rat osteoclast resorption and apoptosis assays and in human mesenchymal stem cell-derived osteoblast assay. We found that due to high bisphosphonate-bone binding affinity, bone surface exposure to clodronate for 3 min. had maximal resorption inhibition. The mechanism of action of both clodronate and zoledronic acid involved osteoclast apoptosis, whereas pamidronate had only minor apoptotic effect at dosages, which readily inhibited resorption. Zoledronic acid was not metabolised into an intracellular ATP-analogue in vitro in contrast to clodronate. All bisphosphonates had a dose-dependent inhibitory effect on the human bone marrow mesenchymal stem cell (hMSC)-derived osteoblast calcium deposition. None of the compounds had inhibitory effect on hMSC differentiation. Zoledronic acid was the most potent of all three bisphosphonates in terms of both apoptosis induction and resorption inhibition. Zoledronic acid efficacy might thus use its capacity to trigger osteoclast apoptosis in an unknown, but similar manner to that of the non-nitrogen-containing bisphosphonates. It appears that zoledronic acid has properties of both bisphosphonate classes and could well be the first member of a new class of bisphosphonates, by definition.

Effect of zoledronic acid used in the root surface treatment of late replanted teeth: a study in rats

“…This emphasizes the zoledronic acid (14)(15)(16)(17)(18)(19)(20) and sodium fluoride (10,11) characteristics in limiting the resorptive process.…”

“…According to several studies, zoledronic acid can be considered the most potent inhibitor of bone resorption, when compared with other biphosphonates (16,17,19). Furthermore, according to Schindeler and Little (17), zoledronic acid does not act on further cells of the body, having its action potential only on clasts.…”

“…Among the several types of biphosphonates, it has currently been highlighted the zoledronic acid (16,19). According to several studies, zoledronic acid can be considered the most potent inhibitor of bone resorption, when compared with other biphosphonates (16,17,19).…”

“…Currently, biphosphonates have been the most important drugs for bone resorption treatment (2,(14)(15)(16)(17)(18)(19)(20). The main mechanisms of action of the drugs have been: drug interference on clastic cells action, apoptosis of these cells, stimulation of blastic cells proliferation or associations of these aforementioned actions (2,14,(16)(17)(18)(19).…”

“…The main mechanisms of action of the drugs have been: drug interference on clastic cells action, apoptosis of these cells, stimulation of blastic cells proliferation or associations of these aforementioned actions (2,14,(16)(17)(18)(19).…”