The effect of the bisphosphonate, Alendronate, on primary human alveolar bone cells
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Background. Bisphosphonates are synthetic analogues of inorganic pyrophosphate. Bisphosphonates are the most commonly antiresorptive agents used in the treatment of diseases involving excessive osteoclast activity, such Paget's disease, tumor associated bone disease and osteoporosis. Bisphosphonates have been shown to inhibit osteoclast-mediated bone resorption and to have anabolic effects on osteoblasts by promoting osteoblast proliferation and maturation. Bisphosphonate-associated osteonecrosis in oral cavity is a major complication associated with bisphosphonates in particularly in the intravenous class. We hypothesized that bisphosphonates have a proliferative and osteogenic effects on osteoblasts obtained from alveolar bone, distinct from the effects on osteoblasts obtained from other parts of the body. The aim of this study was to determine if the bisphosphonate, Alendronate, may enhance or inhibit the proliferation and osteogenesis of primary human osteoblasts derived from alveolar bone cells and to compared the effect of Alendronate alone to PDGF, PTH and to a mixture of Alendronate and either one of these hormones. Methods. Human alveolar bone cells were obtained during routine oral surgical procedure from healthy adult subjects. Following treatment with Alendronate (at 10 -8 M), PDGF, PTH and a combination of Alendronate and either PDGF and PTH at different time periods (24, 48 and72 hours), cells were examined for maturation with the alkaline phosphates assay and RT-PCR for gene expression. The effect of Alendronate on proliferation was assessed with the 3 H-thymidine assay. The results were analyzed by (ANOVA) followed by Tukey HSD post hoc comparison analysis. Results. Alendronate increased alkaline phosphatase activity at 24 and 48 hours. The Proliferation rate was enhanced by Alendronate at 48 hours. Alendronate decreased the gene expression of type I collagen at 24 and 48 hours but promoted the expression at 72 hours. Mixing Alendronate and PDGF decreased the alkaline phosphatase activity at 24 and 48 hours and also decreased the proliferation rate at 48 hours but enhanced the gene expression of type I collagen at all time points, whereas combining Alendronate and PTH decreased the proliferation rate and the gene expression. Conclusion. Alendronate demonstrates positive anabolic effects on primary human osteoblasts derived from alveolar bone. There is no evidence of synergy between Alendronate and PTH, but the possibility exists that PDGF may decrease the osteogenic effect of the bisphosphonate.