Endogenous tissue engineering: PTH therapy for skeletal repair.
Endogenous tissue engineering: PTH therapy for skeletal repair.
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DOI：
10.1007/s00441-011-1188-4
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发表时间：
2012-03
影响因子：
3.6
通讯作者：
Schwarz, Edward M.
中科院分区：
文献类型：
--
作者：
Takahata, Masahiko;Awad, Hani A.;O'Keefe, Regis J.;Bukata, Susan V.;Schwarz, Edward M.
基于重组甲状旁腺激素 (PTH1-34) 对骨质疏松症患者骨骼的合成代谢作用已得到证实，已被评估为骨骼修复的潜在疗法。动物研究调查了 PTH1-34 在各种骨骼修复模型中的作用，例如骨折、同种异体移植、脊柱关节固定术和牵引成骨。这些研究表明，间歇性 PTH1-34 治疗可通过多种机制增强和加速骨骼修复过程，其中包括对间充质干细胞 (MSC)、血管生成、软骨生成、骨形成和骨吸收的影响。此外，PTH1-34 被证明可以在衰老、炎症性关节炎和糖皮质激素引起的骨质流失等具有挑战性的动物模型中增强骨修复。这一临床前的成功导致了超说明书临床使用，并且已经发表了许多记录 PTH1-34 治疗延迟愈合和不愈合的病例报告。此外，PTH1-34治疗桡骨骨折患者的2期临床试验现已完成。尽管该试验未能实现其主要结果（主要是由于安慰剂组的有效愈合），但一些次要结果具有统计学意义，强调了有关适合骨骼修复的 PTH1-34 治疗的患者群体的几个重要问题。在此，我们回顾了目前对 PTH1-34 疗法对骨愈合影响的了解，列举了几个尚未解决的关键问题（例如适当的给药方案和适应症），并讨论了该药物作为内源性组织工程佐剂的长期潜力。
Based on its proven anabolic effects on bone in osteoporosis patients, recombinant parathyroid hormone (PTH1-34) has been evaluated as a potential therapy for skeletal repair. Research in animals has investigated the effect of PTH1-34 in various skeletal repair models such as fractures, allografting, spinal arthrodesis, and distraction osteogenesis. These studies demonstrated that intermittent PTH1-34 treatment enhances and accelerates the skeletal repair process via a number of mechanisms, which includes effects on mesenchymal stem cells (MSC), angiogenesis, chondrogenesis, bone formation and resorption. Furthermore, PTH1-34 was demonstrated to enhance bone repair in challenging animal models of aging, inflammatory arthritis and glucocorticoid-induced bone loss. This pre-clinical success has led to off-label clinical use, and a number of case reports documenting PTH1-34 treatment of delayed-unions and non-unions have been publish. Moreover, a phase 2 clinical trial of PTH1-34 treatment of patient with a radius fracture has now been completed. Although this trial failed to achieve its primary outcome, largely due to effective healing in the placebo group, several secondary outcomes were statistically significant, highlighted several important issues about the appropriate patient population for PTH1-34 therapy for skeletal repair. Here we review our current knowledge of the effects of PTH1-34 therapy for bone healing, enumerate several critical unresolved issues (e.g. appropriate dosing regimen and indications), and discuss this drug’s long term potential as an adjuvant for endogenous tissue engineering.
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影响因子：
6.2
作者：
Andreassen, TT;Ejersted, C;Oxlund, H
通讯作者：
Oxlund, H
影响因子：
15.9
作者：
Jilka, RL;Weinstein, RS;Manolagas, SC
通讯作者：
Manolagas, SC
影响因子：
6.2
作者：
Li, G;White, G;Marsh, D
通讯作者：
Marsh, D
DOI：
10.2106/00004623-200300003-00014
发表时间：
2003-01-01
影响因子：
5.3
作者：
Einhorn, TA
通讯作者：
Einhorn, TA
影响因子：
6.2
作者：
Kakar, Sanjeev;Einhorn, Thomas A.;Barnes, George L.
通讯作者：
Barnes, George L.