Bisphosphonate-associated osteonecrosis of the jaw (BP-ONJ) is one of the most often seen side effects in patients treated with
bisphosphonates, presenting clinically as a non-healing wound. One theory of BP-ONJ etiology describes a negative effect on soft tissues, especially on keratinocytes, which play an important role in oral wound healing and oral soft tissue regeneration. A high cell viability of keratinocytes, which can migrate to the affected location, is essential for wound healing. The aim of this in vitro study was to investigate the effect of differently potent
bisphosphonates on human oral keratinocytes (HOK).Three
nitrogen-containing
bisphosphonates (
ibandronate,
pamidronate, and
zoledronate) and one non-
nitrogen-containing
bisphosphonate (
clodronate) were compared concerning their potency on cell viability (
calcein assay and MTT assay), migration ability (Boyden chamber migration assay and scratch
wound proliferation assay), and apoptosis (TUNEL assay) of HOK.The
nitrogen-containing
bisphosphonates, particularly highly potent
pamidronate and
zoledronate preparations, had a strong negative influence on cell viability, migration ability, and apoptosis of HOK. The non-
nitrogen-containing
clodronate even increased cell viability in higher concentrations.This study demonstrates that
bisphosphonates have a strong influence on HOK on different cellular levels like cell viability, migration ability, and apoptosis rate. The results support the theory that BP-ONJ is a multifactorially caused disease.Furthermore, this in vitro study confirms the theory that perioperative interruption of
bisphosphonate application during dental
surgical procedures might be feasible to promote better tissue regeneration and wound healing.