Evaluation of the bisphosphonate effect on stem cells derived from jaw bone and long bone rabbit models: A pilot study

Abstract Background and objective Bisphosphonates have been widely used and the number of patients experiencing medication-related osteonecrosis of the jaw (MRONJ) has been increasing. This study was designed to evaluate the effect of zoledronate on stem cells derived from different tissues. Design Stem cells derived from four different tissues were compared using rabbit models (JPO: periosteum from the jaw bone (mandible), JBM: bone marrow from the jaw bone, LPO: periosteum from long bone (tibia), and LBM: bone marrow from long bone). Stem cells were grown in the presence of zoledronate at final concentrations ranging from 10 −6  M to 10 −10  M. Morphology was viewed under an inverted microscope, and the analysis of cell proliferation was performed using a Cell Counting Kit-8 (CCK-8) on days 1, 2, 4, and 7. Results The CCK-8 results for LBM showed that the increase of CCK-8 values was correlated with a longer incubation time. Compared to the untreated control, growth in the presence of zoledronate at 10 −10  M and 10 −8  M resulted in decreased CCK-8 values for LBM on day 7 ( P   0.05). The CCK-8 results for JBM, LPO, and JPO on days 1, 2, 4, and 7 showed that the presence of zoledronate did not produce statistically significant changes compared with the untreated control. Conclusion Zoledronate in the tested concentrations from JBM, LPO, and JPO did not produce noticeable alterations in the viability of mesenchymal stem cells. This in vitro experiment suggests that the occurrence of MRONJ solely in the oral cavity is not due to differences in the cellular proliferation of stem cells in the response to zoledronate.