Central Drug Research Institute (Council of Scientific and Industrial Research), Division of Endocrinology, Lucknow, India.
Expert Opin Investig Drugs. 2010 Aug;19(8):995-1005. doi: 10.1517/13543784.2010.501077.
Anabolic therapy, or stimulating the function of bone-forming osteoblasts, is the preferred pharmacological intervention for osteoporosis.
We reviewed bone anabolic agents currently under active investigation. The bone anabolic potential of IGF-I and parathyroid hormone-related protein is discussed in the light of animal data and human studies. We also discuss the use of antagonists of the calcium-sensing receptor (calcilytics) as orally administered small molecules capable of transiently elevating serum parathyroid hormone (PTH). Further, we reviewed novel anabolic agents targeting members of the wingless tail (Wnt) signaling family that regulate bone formation including DKK-1, sclerostin, Thp1, and glycogen synthase kinase 3beta. We have also followed up on the promise shown by beta-blockers in modulating the activity of sympathetic nervous system, thus affecting bone anabolism. We give critical consideration to neutralizing the activity of activin A, a negative regulator of bone mass by soluble activin receptor IIA, as a strategy to promote bone formation.
Update on various strategies to promote osteoblast function currently under evaluation.
In spite of favorable results in experimental models, none of these strategies has yet achieved the ultimate goal of providing an alternative to injectable PTH, the sole anabolic therapy in clinical use.
合成代谢疗法，或刺激成骨细胞（骨形成细胞）的功能，是骨质疏松症的首选药物干预方法。
我们回顾了目前正在积极研究的骨合成代谢药物。根据动物数据和人类研究，讨论了 IGF-I 和甲状旁腺激素相关蛋白的骨合成代谢潜力。我们还讨论了钙敏感受体（calcilytics）拮抗剂的用途，作为能够短暂升高血清甲状旁腺激素（PTH）的口服小分子。此外，我们还综述了针对调节骨形成的 Wnt 信号家族成员的新型合成代谢药物，包括 DKK-1、sclerostin、Thp1 和糖原合酶激酶 3β。我们还跟踪了β受体阻滞剂在调节交感神经系统活性方面的作用，从而影响骨合成代谢。我们对通过可溶性激活素受体 IIA 中和激活素 A 的活性以促进骨形成的策略给予了批判性的考虑，激活素 A 是骨量的负调节剂。
目前正在评估的各种促进成骨细胞功能的策略的最新信息。
尽管在实验模型中取得了有利的结果，但这些策略都没有达到提供替代注射用甲状旁腺激素的最终目标，甲状旁腺激素是唯一在临床使用的合成代谢疗法。
