Bisphosphonates can bind to hydroxyapatite crystals in a mineralized bone matrix and increase bone resistance against osteoclasts. The relative contributions of these properties differ among individual bisphosphonates, and can help determine their clinical behavior and effectiveness. Appropriate doses of bisphosphonates appear to prevent the loss of alveolar bone on density and height, and promote angiogenesis and bone tissue repair. The anti-resorptive effects of nitrogen-containing bisphosphonates on osteoclasts appear to result from their properties as potent inhibitors of farnesyl pyrophosphate synthase. Bisphosphonates can decrease the relative ratio of the receptor activator of nuclear factor-κB ligand/osteoprotegerin, which determines the progress of bone metabolism and degree of bone resorption. Some studies have shown that bisphosphonates can decrease matrix metalloproteinase expression in the periapical area, and inhibit bone resorption. Other studies demonstrated that bisphosphonates can maintain the levels of bone-specific alkaline phosphatase(BAKP) in alveolar bone, and the decrease in BAKP in periodontitis can exacerbate the inflammatory response and periodontal tissue damage.
