Affiliation:
1. Department of Oral Surgery, Medical University of Vienna, Währingerstrasse 25a, A-1090 Vienna, Austria; and
2. Austrian Cluster for Tissue Regeneration, Austria
Abstract
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.
Reference30 articles.
1. Allen MR, Burr DB (2009). The pathogenesis of bisphosphonate-related osteonecrosis of the jaw: so many hypotheses, so few data. J Oral Maxillofac Surg 67(5 Suppl):61S–70S.
2. Once-Yearly Zoledronic Acid for Treatment of Postmenopausal Osteoporosis
3. Renal Failure with the Use of Zoledronic Acid
4. Pharmacokinetics and Pharmacodynamics of Zoledronic Acid in Cancer Patients with Bone Metastases
5. Corey E, Brown LG, Quinn JE, Poot M, Roudier MP, Higano CS, et al. (2003). Zoledronic acid exhibits inhibitory effects on osteoblastic and osteolytic metastases of prostate cancer. Clin Cancer Res 9:295-306
Cited by
56 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献