Abstract
Objectives
To evaluate the effects of sodium alendronate (SA) and zoledronic acid (ZA), on the adhesion and metabolism of epithelial cells and gingival fibroblasts to titanium surfaces considering cell functions related to an effective mucosal barrier around the implant.
Materials and methods
Cells were seeded onto titanium discs and incubated for 24 h. Then, serum-free DMEM containing selected bisphosphonates (0, 0.5, 1, or 5 μM) was added for 24 and 48 h. Factors related to the achievement of an effective mechanical and immunological barrier—cell adhesion, viability, collagen epidermal growth factor, and immunoglobulin synthesis—were evaluated. Data were analyzed by Kruskal-Wallis and Mann-Whitney tests as well as by ANOVA and Tukey’s tests, (α = 0.05).
Results
The presence of bisphosphonates culminated in lower cell adhesion to the titanium discs, particularly for SA at 5 μM (40%) and ZA at all concentrations (from 30 to 50%, according to increased concentrations). Reduced cell viability occurred after exposing these cells to ZA (40%); however, only 5 μM SA-treated cells had decreased viability (30%). Reduced synthesis of growth factors and collagen was observed when cells were reated with ZA (20 and 40%, respectively), while about 70% of IgG synthesis was enhanced.
Conclusion
Bisphosphonates negatively affected the adhesion and metabolism of oral mucosal cells, and this effect was related to the type of bisphosphonate as well as to concentration and period of treatment.
Clinical relevance
The negative effects of bisphosphonates on oral mucosal cells can hamper the formation of an effective biological seal in osseointegrated implants.
Similar content being viewed by others
References
Rogers MJ, Gordon S, Benford HL et al (2000) Cellular and molecular mechanisms of action of bisphosphonates. Cancer 88:2961–2978
Russell RG (2011) Bisphosphonates: the first 40 years. Bone 49:2–19
Simon MJK, Niehoff P, Kimming B, Açil Y (2010) Expression profile and synthesis of different collagen types I, II, III and V of human gingiva fibroblasts, osteoblasts, and SaOS-2 cells after bisphosphonate treatment. Clin Oral Invest 14:51–58
Walter C, Klein MO, Pabst A, Al-Nawas B, Duschner H, Ziebart T (2010) Influence of bisphosphonates on endothelial cells, fibroblasts, and osteogenic cells. Clin Oral Invest 14:35–41
Basso FG, Pansani TN, Oliveira CF et al (2013) Cytotoxic effects of zoledronic acid on human epithelial cells and gingival fibroblasts. Braz Dent J 24:551–558
Basso FG, Turrioni APS, Hebling J, de Souza Costa CA (2013) Zoledronic acid inhibits human osteoblast activities. Gerontology 59:534–541
Migliorati CA, Casiglia J, Epstein J, Jacobsen PL, Siegel MA, Woo S (2005) Managing the care of patients with bisphosphonate-associated osteonecrosis. JADA 136:1658–1668
Woo S, Hellstein JW, Kalmar JR (2006) Systematic review: bisphosphonates and osteonecrosis of the jaws. Ann Intern Med 144:753–761
Diel IJ, Fogelman I, Al-Nawas B et al (2007) Pathophysiology, risk factors and management of bisphosphonate-associated osteonecrosis of the jaw: is there a diverse relationship of amino and non-aminobisphosphonates? Crit Rev Oncol Hematol 64:198–207
Idris AI, Rojas J, Greis IR, van’t Hof RJ, Ralston SH (2008) Aminobisphosphonates cause osteoblast apoptosis and inhibit bone nodule formation in vitro. Calcif Tissue Int 82:191–201
Orriss IR, Key ML, Colston KW, Arnett TR (2008) Inhibition of osteoblast function in vitro by aminobisphosphonates. J Cell Biochem 106:109–118
Scheper MA, Badros A, Salama AR et al (2009) A novel bioassay model to determine clinically significant bisphosphonate levels. Support Care Cancer 17:1553–1557
Ravosa MJ, Ning J, Liu Y, Stack S (2011) Bisphosphonate effects on the behavior of oral epithelial cells and oral fibroblasts. Arch Oral Biol 56:491–498
Basso FG, Turrioni APS, Soares DG, Bagnato VS, Hebling J, de Souza Costa CA (2014) Low-level laser therapy for osteonecrotic lesions: effects on osteoblasts treated with zoledronic acid. Support Care Cancer 22:2741–2748
Migliorati CA, Woo S, Hewson I et al (2009) A systematic review of bisphosphonate osteonecroses (BON) in cancer. Support Care Cancer 18:1099–1106
Landesberg R, Woo V, Cremers S et al (2011) Potential pathophysiological mechanism in osteonecroses of the jaw. Ann N Y Acad Sci 1218:62–69
Reid IR (2009) Osteonecrosis of the jaw—who gets it and why? Bone 44:4–10
Otto S, Pautke C, Opelz C et al (2010) Osteonecrosis of the jaw: effect of bisphosphonate type, local concentration, and acidic milieu on the pathomechanism. J Oral Maxillofac Surg 68:2837–2845
Madrid C, Sanz M (2009) What impact do systemically administered bisphosphonates have on oral implant therapy? A systematic review. Clin Oral Impl Res 20:87–95
Javed F, Almas K (2010) Osseointegration of dental implants in patients undergoing bisphosphonate treatment: a literature review. J Periodontol 81:479–484
Chadha G, Ahmadieh A, Kumar S, Sedghzadeh PP (2013) Osseointegration of dental implants and osteonecrosis of the jaw in patients treated with bisphosphonate therapy: a systematic review. J Oral Implantol 39:510–520
Taxel P, Ortiz D, Shafer D et al (2014) The relationship between implant stability and bone health markers in post-menopausal women with bisphosphonate exposure. Clin Oral Invest 18:49–57
An N, Rausch-fan X, Wieland M, Matejka M, Andrukhov O, Schedle A (2012) Initial attachment, subsequent cell proliferation/viability and gene expression of epithelial cells related to attachment and wound healing in response to different titanium surfaces. Dent Mater 28:1207–1214
Etminan M, Aminzadeh K, Mathew IR, Brophy JM (2008) Use of oral bisphosphonates and risk of aseptic osteonecrosis: a nested case-control study. J Rheumatol 35:691–695
Khan AA, Sándor GK, Dore E et al (2008) Canadian consensus practice guidelines for bisphosphonate associated osteonecrosis of the jaw. J Rheumatol 35:1391–1397
Bedogni A, Bettini G, Totola A, Saia G, Nocini PF (2010) Oral bisphosphonate-associated osteonecrosis of the jaw after implant surgey: a case report and literature review. J Oral Maxillofac Surg 68:1662–1666
Assael LA (2009) Oral bisphosphonates as a cause of bisphosphonate-related osteonecrosis of the jaws: clinical findings, assessment of risks, and preventive strategies. J Oral Maxillofac Surg 67:35–43
Body JJ, Mancini I (2002) Bisphosphonates for cancer patients: why, how, and when? Support Care Cancer 10:399–407
Hynes RO (1992) Integrins: versatility, modulation and signaling in cell adhesion. Cell 69:11–25
Patidar K, Parwani RN, Wanjari SP (2011) Correlation of salivary and serum IgG, IgA levels wih total protein in oral submucous fibrosis. J Oral Sci 53:97–102
Tilakaratne WM, Klinikowki MF, Saku T, Peters TJ, Warnakulasuriya S (2006) Oral submucous fibrosis: review on aetiology and pathogenesis. Oral Oncol 42:561–568
Acknowledgements
Authors acknowledge the National Council for Scientific and Technological Development – CNPq (Grants: 157779/2015-7, 442637/2014-4, 303599/2014, 307696/2014) for the financial suport.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Funding
The work was supported by the National Council for Scientific and Technological Development – CNPq (Grants: 157779/2015-7, 442637/2014-4, 303599/2014, 307696/2014).
Ethical approval
All procedures were performed in accordance to Ethics Committee of Araraquara School of Dentistry, Unesp, Brazil.
Informed consent
Gingival fibroblasts were isolated after patients agreement by signing of informed consent.
Rights and permissions
About this article
Cite this article
Basso, F.G., Pansani, T.N., Soares, D.G. et al. Influence of bisphosphonates on the adherence and metabolism of epithelial cells and gingival fibroblasts to titanium surfaces. Clin Oral Invest 22, 893–900 (2018). https://doi.org/10.1007/s00784-017-2167-2
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00784-017-2167-2