Effects of Alendronate on Human Alveolar Osteoblastic Cells: Interactions with Platelet-Derived Growth Factor

Introduction: Bisphosphonates are widely used in the treatment of bone disease due to their inhibitory effects on bone remodeling. Although it is well established that bisphosphonates act by direct effects on osteoclastic cells, there has been increasing evidence suggesting that they may also work on osteoblast cells. The reported effects of these drugs on osteoblast cells are conflicting with increasing number of studies suggesting that at different concentrations, and with different types of bisphosphonates osteoblast differentiation and bone formation activities are varied. Side effects such as osteonecrosis of the jaw are seen with chronic use of bisphosphonates. To better develop approaches to minimize these adverse effects it is important tofurther understand the effects of bisphosphonates on osteoblasts and their modulation by endogenous regulatory factors. Materials and Methods: Human alveolar osteoblastic cell cultures were treated with the bisphosphonate, alendronate, platelet derived growth factor and a combined treatment of alendronate and platelet derived growth factor. Cell activity was assessed with a mitochrondrial enzyme assay, and differentiation with spectrophotometric assays for alkaline phosphatase and mineralization over a period from 24 hours to 17 days. Results and Conclusion: Treatment of the osteoblastic cells with alendronate (10-8 M) produced small, significant effects on cell activity and markers of differentiation that varied with the time of incubation. The effects of platelet derived growth factor on these same parameters were maintained with co-incubation with alendronate suggesting this growth factor may have a therapeutic role in the minimization of the negative side effects of the drug. These data are supportive of the emerging potential of the clinical use of platelet growth factor enriched plasma for bisphosphonate-induced osteonecrosis of the jaw.