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KMID : 1007020080060020063
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Korean Soceity of Osteroporosis
2008 Volume.6 No. 2 p.63 ~ p.70
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Mode of Action of Bisphosphonates and Clinical Implication
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Choi Hee-Jeong
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Abstract
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Nitrogen-containing bisphosphonates are potent inhibitors of osteoclastic activity that are now widely used for preventing the bone loss associated with osteoporosis, Paget\’s disease, hypercalcemia and metastatic bone disease. The clinical efficacy of bisphosphonate is determined by the bone mineral binding affinity and the extent of inhibition of farnesyl pyrophosphate synthase, a target enzyme of bisphosphonate. Each bisphosphonate has unique structural properties. The structure-function profile of individual bisphosphonates is determined by R1 and R2 side chains. Bone binding affinity is enhanced when R1 side chain is a hydroxyl group. The R2 side chains determines the antiresorptive potency of the bisphosphonate but has some effect on binding. The nitrogen moiety within the R2 side chain potentiate the FPPS inhibitory action of bisphosphonate. Structural differences among bisphosphonates explain the observed differences in mineral binding affinity and antiresorptive potency and may in turn account for some of clinical differences that have been seen in potency, disease-specific efficacy, speed of onset, offset of action and antifracture efficacy in various clinical trials.
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KEYWORD
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Osteoporosis, Bisphosphonate, MOA
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