Is zoledronate toxic to human periodontal fibroblasts?
Exposed necrotic alveolar bone is a hallmark of bisphosphonate-related osteonecrosis of the jaw. However, it is unknown whether zoledronate causes soft-tissue damage via adverse actions toward periodontal fibroblasts. We therefore examined whether zoledronate causes a cytotoxic response in fibroblasts isolated from the gingiva and the periodontal ligament. We report that micromolar concentrations of zoledronate and serum-free conditions decreased cell activity, as measured by assays for formazan formation, proliferation, and protein synthesis. Under these conditions, periodontal fibroblasts underwent apoptosis and necrosis, as indicated by cleavage of PARP and membrane disruption, respectively. However, these adverse effects of zoledronate were mitigated by the presence of serum. Moreover, zoledronate bound to calcium phosphate failed to reduce cell activity. Analysis of these data suggests that the cytotoxic responses of periodontal fibroblasts require high concentrations of zoledronate and depend on the in vitro experimental conditions. Whether these findings translate into soft-tissue damage will require further investigation.
Agis
H
H
Department of Oral Surgery, Medical University of Vienna, Währingerstrasse 25a, A-1090 Vienna, Austria.
Blei
J
J
Watzek
G
G
Gruber
R
R
D017209:Apoptosis / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000633:toxicity*; D018929:Cell Culture Techniques; D002478:Cells, Cultured; D004164:Diphosphonates / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D005562:Formazans / Q000378:metabolism; D005881:Gingiva / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007093:Imidazoles / Q000633:toxicity*; D010513:Periodontal Ligament / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D012016:Reference Values; D013997:Time Factors; D000077211:Zoledronic Acid
D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D005562:Formazans; D007093:Imidazoles; D000077211:Zoledronic Acid