科研之友
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摘要
In order to treat systemic bone loss in osteoporosis, most approaches target the osteoclasts - the cells resorbing bone. Drugs inhibiting the differentiation, activity and/or survival of osteoclasts have, thus, become a fundamental option for the prevention and treatment of osteoporosis. In general, this class includes estrogens and selective estrogen receptor modulators, but, first of all, bisphosphonates and denosumab. Bisphosphonates are currently the most widely used antiresorptive therapy. They act by binding to bone and interfering with osteoclast function. The nitrogen-containing bisphosphonates act as inhibitors of farnesyl-pyrophosphate synthase, which leads to inhibition of the prenylation of intracellular proteins. The recent discovery of the RANK/RANKL/OPG system and its essential role in the osteoclast differentiation, activity and survival, have led to the development of denosumab - an innovative treatment option. This fully human monoclonal antibody acts by binding to and inhibiting RANK-Ligand (RANKL), leading to the inhibition of osteoclast differentiation, its activity and survival and, finally, to a loss of osteoclasts from bone surfaces. Bisphosphonates, such as alendronate, risedronate, ibandronate and zoledronate, as well as the RANKL-inhibitor denosumab have been approved for the treatment of osteoporosis and have shown robust efficacy data in reference to fracture prevention. The key pharmacological differences between denosumab and bisphosphonates are a result of the distribution of the drugs within bone and their effects on precursors and mature osteoclasts. This may explain differences in the degree of reduction of bone resorption, their potential differential effects on trabecular and cortical bone, and the reversibility of their actions. Basic knowledge of the differences in mode of action of these drugs is also essential to understanding of their potential association with osteonecrosis of the jaw (ONJ) and to development of differentiated and sufficient ONJ prevention and treatment strategies.
- 出版日期2012
