Bisphosphonates and implantology: effect of metalloproteinases inhibitors in in vitro model

Abstract

Bisphosphonates are indicated for treatment of osteolytic diseases, aiming to control bone resorption. These drugs show high affinity to mineral tissues and are released during traumatic or inflammatory events, leading to cytotoxic and cytopatic effects. For this reason, the installation of oral osseointegrated implants is still controversial for patients ongoing bisphosphonates treatment. Besides the cytotoxic effects, bisphosphonates may also induce the overexpression of matrix metalloproteinases (MMPs), negatively interfering on osseointegration and biological sealing. Therefore, the modulation of these enzymes could favor these tissue events. The aim of this study will be to evaluate the effect of two MMPs inhibitors - proanthocyanidins and naringenin, on osteoblasts and fibroblasts seeded onto titanium surfaces and treated with Zoledronic Acid (ZA). Titanium discs will be placed in cell-culture plates and cells will be seeded onto them. After 24 hours, ZA will be applied and after 24 or 48 hours cell proliferation, adhesion, collagen synthesis, alkaline phosphatase activity, gene expression, synthesis and activity of MMPs will be evaluated. Expression of TIMP-1 and -2 will also be assessed. Results will be statistically evaluated according to data distribution. (AU)