Laboratory of Osteoblast Biology and Pathology, INSERM, U606, Hospital Lariboisiere, 2 Rue Ambroise Pare, 75475 Paris Cedex 10, France.
Eur J Endocrinol. 2011 Jul;165(1):1-10. doi: 10.1530/EJE-11-0132. Epub 2011 May 4.
Age-related bone loss is associated with significant changes in bone remodeling characterized by decreased trabecular and periosteal bone formation relative to bone resorption, resulting in bone fragility and increased risk of fractures. Prevention or reversal of age-related decrease in bone mass and increase in bone fragility has been based on inhibition of bone resorption using anticatabolic drugs. The current challenge is to promote osteoblastogenesis and bone formation to prevent age-related bone deterioration.
A limited number of approved therapeutic molecules are available to activate bone formation. Therefore, there is a need for anabolic drugs that promote bone matrix apposition at the endosteal, endocortical, and periosteal envelopes by increasing the number of osteoblast precursor cells and/or the function of mature osteoblasts. In this study, we review current therapeutics promoting bone formation and anabolic molecules targeting signaling pathways involved in osteoblastogenesis, based on selected full-text articles searched on Medline search from 1990 to 2010.
We present current therapeutic approaches focused on intermittent parathyroid hormone and Wnt signaling agonists/antagonists. We also discuss novel approaches for prevention and treatment of defective bone formation and bone loss associated with aging and osteoporosis. These strategies targeting osteoblastic cell functions may prove to be useful in promoting bone formation and improving bone strength in the aging population.
与年龄相关的骨质流失与骨重塑的显著变化相关，其特征为相对于骨吸收，骨小梁和骨皮质形成减少，导致骨脆弱和骨折风险增加。预防或逆转与年龄相关的骨量减少和骨脆性增加一直基于使用抗分解代谢药物抑制骨吸收。目前的挑战是促进成骨细胞生成和骨形成，以防止与年龄相关的骨恶化。
目前仅有数量有限的经批准的治疗分子可用于激活骨形成。因此，需要有促进成骨细胞前体细胞数量增加和/或成熟成骨细胞功能的合成代谢药物，以增加骨基质在骨内膜、骨皮质和骨膜表面的附着。在这项研究中，我们根据从 1990 年到 2010 年在 Medline 搜索中检索到的选定全文文章，综述了目前促进骨形成的治疗方法和针对成骨细胞发生的信号通路的合成代谢分子。
我们介绍了目前专注于间歇性甲状旁腺激素和 Wnt 信号激动剂/拮抗剂的治疗方法。我们还讨论了预防和治疗与衰老和骨质疏松相关的骨形成缺陷和骨丢失的新方法。这些针对成骨细胞功能的策略可能有助于促进骨形成并改善老年人群的骨强度。
