The purpose of this study is to investigate the effects of
alendronate and
pamidronate on proliferation and the
alkaline phosphatase activity of
human bone marrow derived
mesenchymal stem cells and to relate the results with
bisphosphonate related osteonecrosis of the jaw(BRONJ). With the consent of
patients with no systemic
disease and undergoing iliac
bone graft,
cancellous bone was collected to obtain
human bone marrow derived
mesenchymal stem cells through
cell culture. 96 well plate were prepared with a concentration of 10(4)
cell/ well.
Alendronate and
pamidronate were added to each well with the concentration of 10(-6)M, 10(-8)M and 10(-10)M, respectively. Then proliferation capacity of each well was evaluated with the
cell counting kit. 24 well plates were prepared with a concentration of 10(5)
cell/ml/well and with the
bone supplement,
alendronate and
pamidronate were added with the concentration of 10(-6)M, 10(-8)M and 10(-10)M, respectively on each plate. The plates were cultured for either 24 or 72 hours. Then the
cells were sonicated to
measure the
alkaline phosphatase activity and
protein assay was done to standardize the data for
analysis. As the concentration of
alendronate or
pamidronate added to the
culture increased, the proliferation capacity of the
cells decreased. However, no statistical significance was found between the group with 10(-10)M of bisphophonate and the
control group.
Pamidronate was not capable of increasing the
alkaline phosphatase activity in all trials. However,
alkaline phosphatase activity increased with 24 hours of 10(-8)M of
alendronate treatment and with 48 hours of 10(-10)M of
alendronate treatment.
Cell toxicity increased as the
bisphosphonate concentration increased. This seems to be associated with the long
half life of
bisphosphonate, resulting in high concentration of
bisphosphonate in the
jaw and thus displaying delayed healing after
surgical procedures.
Alendronate has shown to increase the alkaline phophatase activity of
human bone marrow derived
mesenchymal stem cells. However, this data is insufficient to conclude that
alendronate facilitates the differentiation of
human bone marrow derived
mesenchymal stem cells. Further studies on
DNA level and
animal studies are required to support these results.