The Combined Use of Bisphosphonates and Strontium Ranelate with Osseosubstituting Materials

Abstract

In review the possibility of biomaterials osseointegration improvement with help of bisphosphonates or strontium ranelate is discussed. For this purpose, they are added to hydroxyapatite used for implants coating, or are included as a component of bulk calcium phosphate materials. Strontium is employed as a compound of biodegradable metal alloys, also. Combined use of carrier (implant) with bisphosphonates or strontium ranelate promotes controlling local delivery of pharmaceutical molecules into lesion, enhances the therapy efficiency, and decreases a dose and systemic toxicity of the drugs. Bisphosphonates and strontium ranelate increase the mass, a count and thickness of bone trabeculas, improve the bone biomechanical properties in the place of implants fixation, and diminish the bone fracture risk. Main studies are devoted to pharmacologic mechanisms of implants osseointegration improvement. Bisphosphonates as isoprenoid lipids chemical analogues diminish by concurrent principle the osteoclasts farnesyl pyrophosphate synthase activity and inhibit the prenylation. Unprenylated small GTPases don't fasten onto osteoclasts membrane that weakens cellular resorptive activity and accelerates their apoptosis. Strontium ranelate enhances osteoblasts replicative activity and suppresses their apoptosis, also retards osteoclasts resorptive function and accelerates their apoptosis. Its effects are conditioned by activating Wnt-signaling pathway by means of calcium-sensing receptor and by changing the RANKL/RANK/OPG system.