Matsumoto Toshio
Nihon Rinsho. 2015 Oct;73(10):1639-44.
Bone is constantly remodeled to maintain its volume, structural integrity and strength Currently available bone anabolic agent is teriparatide. Teriparatide increases bone mass and strength via both remodeling-dependent and -independent mechanisms, although remodeling-dependent mechanism overweighs the other. Canonical Wnt signal plays an important role in enhancing osteoblast differentiation and bone formation, and its osteocyte-derived inhibitor, sclerostin, regulates bone formation via the regulation of Wnt signaling. Anti-sclerostin antibody stimulates Wnt signaling and enhances bone formation. Phase II clinical trials with anti-sclerostin antibodies, romosozumab and blosozumab, demonstrated a marked increase in bone mineral density after one year of treatment. The new modality of anabolic agents via remodeling-independent stimulation of bone formation may open up a new avenue for the treatment of osteoporosis.
骨骼会不断进行重塑以维持其体积、结构完整性和强度。目前可用的骨合成代谢药物是特立帕肽。特立帕肽通过依赖重塑和不依赖重塑的机制增加骨量和强度,尽管依赖重塑的机制更为重要。经典Wnt信号在增强成骨细胞分化和骨形成中起重要作用,其骨细胞衍生的抑制剂硬化蛋白通过调节Wnt信号来调节骨形成。抗硬化蛋白抗体刺激Wnt信号并增强骨形成。使用抗硬化蛋白抗体罗莫单抗和布洛索单抗进行的II期临床试验表明,治疗一年后骨矿物质密度显著增加。通过不依赖重塑刺激骨形成的合成代谢药物新方式可能为骨质疏松症的治疗开辟一条新途径。