Tzioupis Christopher C, Giannoudis Peter V
Academic Department of Orthopedic and Trauma Surgery, School of Medicine, University of Leeds, St. James's University Hospital, Beckett Str., LS9 7TF Leeds, UK.
Curr Drug Saf. 2006 May;1(2):189-203. doi: 10.2174/157488606776930571.
Osteoporosis is characterized by low bone mineral density and deterioration in the microarchitecture of bone that increases its fracture vulnerability. The mainstay of therapy for osteoporosis is anti-resorptive in mechanism. Parathyroid hormone (PTH) is the most recently approved anabolic agent for osteoporosis. The mechanism of PTH's skeleton anabolic action is composite involving pathways linked to common signalling peptides that affect gene osteoblast transcription. A number of animal studies and clinical trials have demonstrated that intermittent PTH administration induces anabolic effects on both cancellous and cortical bone, enhances bone mass and increases mechanical bone strength, increasing spine and hip bone mineral density and reducing fragility fractures. Preclinical studies investigating the effect of PTH on fracture healing show an increase in bone density and strength indicating an enhancement of this biological cascade. Preclinical and clinical safety assessments have revealed little evidence of toxic effects and there have been few reports of adverse events related to their use. An increase in osteosarcoma in rats probably is not prognostic of an equivalent possibility in humans. In summary, parathyroid hormone is a major advance in the treatment of osteoporosis. Additional studies addressing long-term clinical safety are needed. However the current evidence is very promising.
骨质疏松症的特征是骨矿物质密度低以及骨骼微结构恶化，从而增加了骨折易感性。骨质疏松症治疗的主要手段在机制上是抗吸收的。甲状旁腺激素（PTH）是最近被批准用于治疗骨质疏松症的促合成代谢药物。PTH对骨骼的促合成代谢作用机制是复合性的，涉及与影响成骨细胞基因转录的常见信号肽相关的途径。多项动物研究和临床试验表明，间歇性给予PTH可对松质骨和皮质骨产生促合成代谢作用，增加骨量并提高骨骼机械强度，增加脊柱和髋部的骨矿物质密度并减少脆性骨折。研究PTH对骨折愈合影响的临床前研究显示骨密度和强度增加，表明这种生物学级联反应得到增强。临床前和临床安全性评估几乎没有发现毒性作用的证据，且很少有与其使用相关的不良事件报告。大鼠骨肉瘤的增加可能并不预示人类有同等可能性。总之，甲状旁腺激素是骨质疏松症治疗方面的一项重大进展。需要进行更多关于长期临床安全性的研究。然而，目前的证据非常有前景。
