Petcu, E., Sharma, D., Hamlet, S., and Ivanovski, S. (2015) Osteogenic differentiation of mesenchymal stem cells is affected by alendronate. Tissue Engineering. Part A, 21 (S1). pp. 348-349.

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Abstract

Objectives: Various conditions like osteoporosis and Paget’s disease show altered bone homeostasis skewed towards increased resorption warranting use of anti-resorptive drugs like Alendronate (nitrogen-containing bisphosphonate). However, a prominent side effect of alendronate is medication induced osteonecrosis of jawbone (previously termed BRONJ). Although in-vitro and in-vivo studies have shown that Alendronate affects bone cells, gingival fibroblasts and local vascularity, literature evaluating the influence of alendronate on pluripotent stem cells is distinctly lacking. Thus, our in-vitro study was aimed at evaluating the effects of alendronate on the proliferation, osteogenic differentiation and mineralization potential of human mesenchymal stem cells (MSCs).

Methods: MSCs were cultured in-vitro with alendronate at0.25 mM, 0.5 mM, 1 mM, 2 mM and 3 mM in culture media for 10 days and proliferation was assessed using an Alamar Blue assay. Live-Dead assay was used to determine a suitable concentration for the differentiation assay. Osteogenic differentiation was conducted in osteogenic media over 21 days and Alizarin Red staining was undertaken to confirm mineralization and quantify the staining.

Results: Alamar Blue assay showed that Alendronate was cytotoxicat 2 mM and 3 mM. Optimal alendronate concentration for differentiation of MSCs without causing cell death was 1 mM, as confirmed by the Live-Dead assay. Subsequently, differentiation assay and Alizarin red staining showed mineralization occurred at 21days in differentiation media. Quantification showed that Alendronate significantly affected the functional aspect of differentiated MSCs.

Significance: These findings suggest direct effects of alendronate on MSCs could have a significant role in inhibiting optimal bone remodelling and mineralization thereby ensuing MRONJ.

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