Update in New Anabolic Therapies for Osteoporosis
Update in New Anabolic Therapies for Osteoporosis
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DOI：
10.1210/jc.2009-2677
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发表时间：
2010-04-01
影响因子：
5.8
通讯作者：
Canalis, Ernesto
中科院分区：
文献类型：
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作者：
Canalis, Ernesto
骨合成代谢剂促进骨形成，这是由成骨细胞的数量和功能决定的。细胞数量由调节成骨细胞谱系细胞的复制、分化和死亡的因子控制，而细胞功能由作用于成熟成骨细胞的信号控制。骨形态发生蛋白（BMP）和Wnt诱导间充质细胞向成骨细胞分化，IGF-I增强成熟成骨细胞的功能。BMP、Wnt和IGF-I的活性由蛋白质控制，这些蛋白质通过与生长因子或其受体结合，可以拮抗其作用。这些细胞外拮抗剂的表达或结合亲和力的变化可能与骨形成和骨量的增加或减少有关。骨质疏松症合成代谢治疗的新方法可能包括使用具有合成代谢特性的因子，或中和生长因子拮抗剂。选择的方法包括使用Wnt拮抗剂的中和抗体，通过蛋白酶体抑制剂增强BMP信号传导，或使用激活素可溶性受体、IGF-I或PTH类似物。合成代谢剂需要专门针对骨骼，以避免不必要的非骨骼效应并确保安全性。目前正在进行临床试验，以测试新型骨合成代谢药物的长期有效性和安全性。（临床内分泌代谢杂志95：1496-1504，2010）
Skeletal anabolic agents enhance bone formation, which is determined by the number and function of osteoblasts. Cell number is controlled by factors that regulate the replication, differentiation, and death of cells of the osteoblastic lineage, whereas cell function is controlled by signals acting on the mature osteoblast. Bone morphogenetic proteins (BMP) and Wnt induce the differentiation of mesenchymal cells toward osteoblasts, and IGF-I enhances the function of mature osteoblasts. The activity of BMP, Wnt, and IGF-I is controlled by proteins that, by binding to the growth factor or to its receptors, can antagonize its effects. Changes in the expression or binding affinity of these extracellular antagonists can be associated with increased or decreased bone formation and bone mass. Novel approaches to anabolic therapies for osteoporosis may include the use of factors with anabolic properties, or the neutralization of a growth factor antagonist. Selected approaches include the use of neutralizing antibodies to Wnt antagonists, the enhancement of BMP signaling by proteasome inhibitors, or the use of activin soluble receptors, IGF-I, or PTH analogs. An anabolic agent needs to be targeted specifically to the skeleton to avoid unwanted non-skeletal effects and ensure safety. Clinical trials are being conducted to test the long-term effectiveness and safety of novel bone anabolic agents. (J Clin Endocrinol Metab 95: 1496-1504, 2010)