Bisphosphonates affect migration ability and cell viability of HUVEC, fibroblasts and osteoblasts in vitro.
OBJECTIVE
Bisphosphonate-associated osteonecrosis of the jaw (BP-ONJ) is a side effect in patients being treated with bisphosphonates. The bisphosphonates most often associated with BP-ONJ are the highly potent nitrogen-containing bisphosphonates, e.g. pamidronate or zoledronate. In terms of BP-ONJ aetiology, several theories are being discussed: inhibition of bone remodelling, effect on soft tissues, and antiangiogenic effect of bisphosphonates. The aim of this in vitro study was to investigate the effect of different potent bisphosphonates on osteoblasts, fibroblasts and human umbilicord vein endothelial cells (HUVEC).


METHODS
Three nitrogen-containing bisphosphonates (ibandronate, pamidronate and zoledronate) and one non-nitrogen-containing bisphosphonate (clodronate) were compared concerning their potency on apoptosis induction (tunel), cell viability (calcein assay) and migration potency (boyden chamber) on osteoblasts, fibroblasts and HUVEC.


RESULTS
The nitrogen-containing bisphosphonates, particularly pamidronate and zoledronate, affect cell viability, cell migration and the induction of apoptosis of osteoblasts, fibroblasts and HUVEC.


CONCLUSIONS
These results support the theory that BP-ONJ is a multifactorially caused disease because several cell lines of the oral cavity which are responsible for integrity and wound healing are negatively affected by nitrogen-containing bisphosphonates. Perioperative interruption of bisphosphonate application during dental surgical procedures--if possible--might be feasible to promote better wound healing.
Walter
C
C
Department of Oral- and Maxillofacial Surgery, Plastic Surgery, Johannes-Gutenberg-University Mainz, Mainz, Germany. walter@mkg.klinik.uni-mainz.de
Pabst
A
A
Ziebart
T
T
Klein
Mo
M
Al-Nawas
B
B
D017209:Apoptosis / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000494:pharmacology*; D018929:Cell Culture Techniques; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004002:Clodronic Acid / Q000494:pharmacology; D004164:Diphosphonates / Q000494:pharmacology*; D042783:Endothelial Cells / Q000187:drug effects*; D004730:Endothelium, Vascular / Q000166:cytology; D005347:Fibroblasts / Q000187:drug effects*; D005452:Fluoresceins; D005456:Fluorescent Dyes; D006801:Humans; D000077557:Ibandronic Acid; D007093:Imidazoles / Q000494:pharmacology; D020287:In Situ Nick-End Labeling; D009584:Nitrogen / Q000494:pharmacology; D010006:Osteoblasts / Q000187:drug effects*; D000077268:Pamidronate; D014471:Umbilical Veins / Q000166:cytology; D000077211:Zoledronic Acid
D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D005452:Fluoresceins; D005456:Fluorescent Dyes; D007093:Imidazoles; D004002:Clodronic Acid; D000077211:Zoledronic Acid; D009584:Nitrogen; D000077268:Pamidronate; D000077557:Ibandronic Acid; C007740:fluorexon