Effect of bisphosphonates on the osteogenic activity of osteoprogenitor cells cultured on titanium surfaces

Sher, J.;Miller, C.;Sharma, D.

Abstract

Bone healing around modern titanium based dental implants involves a complex chain of biological events resulting in the formation of new bone on the implant surface and predictable osseointegration. Bisphosphonates (BPs) are known to have potent inhibitory effects on osteoclastic bone resorption, but their effects on the bone forming capabilities of osteoblasts are less well known. This in vitro study investigated the effect(s) of therapeutic doses of BPs on the osteogenic activity of osteoprogenitor cells cultured on titanium surfaces in order to assess whether a perturbation in osteoblastogenesis by BPs could compromise osseointegration and play a role in the pathophysiology of bone healing disorders such as BP-related Osteonecrosis of the Jaw (BRONJ), or conversely, enhance bone healing and osseointegration following implant placement. MC3T3-E1 Subclone 4 cells were utilised in this study. Therapeutic doses of Alendronate (ALN) and Zoledronate (ZA) were calculated based on reported peak plasma concentrations. We tested ALN and ZA at their therapeutic dose concentration equivalent as well as half of this. The viability, proliferation, adhesion, and mineralisation potential of cells was assessed using a LIVE/DEAD stain, alamarBlue assay, immunofluorescence microscopy, and Alizarin Red S staining, respectively. Therapeutic doses of ALN significantly enhanced cell differentiation and mineralisation compared to the untreated group (p = 0.0005). Therapeutic doses of ZA appeared to negatively affect cell viability with notably more dead cells compared to the untreated group, however, overcrowding of cells meant quantification and statistical analysis were not possible. Other than these two findings, there were no other discernible effects on the cells that were noted. The enhancement of cell differentiation and mineralisation following ALN treatment indicates potential for improved bone healing and osseointegration in patients treated with ALN. Conversely, the potentially negative effect of ZA on cell viability may provide some insight into the pathogenesis of BRONJ developing following implant placement in patients treated with ZA.

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Australian Dental Journal

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1834-7819

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Wiley-Blackwell

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