Effects of Bisphosphonates on the Proliferation and the Alkaline Phosphatase Activity of Human Bone Marrow Derived Mesenchymal Stem Cells

ABSTRACT

PURPOSE: The purpose of this study is to find out the effects of bisphosphonates (BPs) on the proliferation and the alkaline phosphatase (ALP) activity of human bone marrow derived mesenchymal stem cells (hMSCs), and thus state its correlation with bisphosphonate related osteonecrosis of the jaw (BRONJ).METHODS: hMSCs was obtained by collecting and culturing cancellous bone fragments from a patient undergoing iliac bone graft. Alendronate (Aln) and Pamidronate (Pam), Ibandronate (Ibn) were added to the culture media in the concentration from 10-3 M to 10-11 M and cell toxicity, viability were measured. For ALP activity evaluation, Aln and Pam were added to the culture media in the concentration from 5x10-7 M to 1x10-8 M and were cultured for 1 week, 2 weeks and 3 weeks. ALP activity data were standardized using protein assay. Control groups were prepared for each examination.RESULTS: Aln, Pam and Ibn all failed to increase the proliferation of hMSCs. With 1 week, 2 weeks of 5x10-8 M of Aln treatment, the ALP activity increased. Pam treatment increased the ALP activity with 2 weeks of 5x10-8 M and 1x10-8 M. Also Ibn treatment increased the ALP activity with 2 weeks of 5x10-8 M and 1x10-8 M.CONCLUSION: It is considered that BPs are not capable of improving the proliferation of hMSCs. Also, after a transient increase in the ALP activity with the lower concentration of BPs, the activity decreased again. Therefore, in patients on long-term medication of BPs, the proliferation and osteoblast differentiation of hMSCs are restrained, and thus delayed wound healing and increase in BRONJ complications may occur.