Improved Treatment of Vertebral Compression Fractures for Elderly Patients Using an Image-Guided, Percutaneous Delivery of a Novel Bone Adhesive

项目摘要 在美国，每年大约有70万例椎体压缩骨折(VCF)，造成 估计有2.5亿美元与医疗保险相关的费用。压缩性骨折最常见的是 患有骨质疏松症的老年人，占美国70岁以上人口的20%。84% 有压缩骨折的放射学证据的患者报告严重的相关背部疼痛。 在历史上，VCFs的治疗主要采用椎体成形术和后凸成形术，这两种技术 涉及经椎弓根将聚甲基丙烯酸甲酯(PMMA)注入椎体 透视下进路。70%到90%的患者使用这些药物治疗后，疼痛得到显著缓解 程序。然而，最近的临床证据表明，这些程序在 因骨质疏松症的潜在状况而放大的重大并发症，包括移植物移位和 生存、种植体固定丧失和交界性后凸畸形。聚甲基丙烯酸甲酯水泥引起的热坏死 邻近的骨组织由于其聚合温度较高。它缺乏生物降解性，加上它的 与松质骨相比，较高的弹性模数(即硬度)也会导致邻近骨折。 脊椎骨。最令人担忧的是渗出或水泥渗漏的风险，这已经发生在高达75%的 所有报告的导致肺栓塞的病例中，高达23%的患者发生在发表的 文学。因此，这些手术的流行率下降了70%以上也就不足为奇了。 从他们的顶峰，因为这一信息已被曝光。然而，不幸的是，这让许多患者 慢性疼痛，没有可行的治疗选择。 为了解决这个问题，RevBio，Inc.开发了Tetranite®(TN)，这是一种新型的骨粘连生物材料，可以 将骨骼碎片粘合在一起，填补骨骼空隙。随着时间的推移，这种专有材料就像一个脚手架，可以 骨骼通过它生长，并最终用新的、有活力的骨骼取代它。研究表明，这种材料是 还能促进骨质疏松患者的骨愈合和骨重塑。TN是经过验证的 可注射性、低放热温度、生物降解性、固有机械强度、无毒性和 粘附性使其能够渗透到松质骨中，使其成为取代PMMA的良好候选材料 能够治疗患有慢性疼痛的VCFs患者。因此，这项拟议的研究 力求实现以下目标：目标1：优化VCFTN的经皮给药 程序和目标2：在一项大型动物先导研究中展示TN的安全和有效使用。 这项先导性动物研究(目标2)的结果，与外科医生验证的模拟使用身体相补充 测试(目标1A)将被用作开发关键动物研究的基础，以发起监管讨论 与食品药品管理局合作。从长远来看，RevBio的使命是为外科医生提供一种能够增强固定能力的新产品 并减少与治疗老年人椎体压缩骨折相关的并发症。

Project Abstract Approximately 700,000 vertebral compression fractures (“VCF”) occur each year in the United States, costing an estimated $250 million in Medicare-related expenses. Compression fractures are most common among elderly individuals with osteoporosis, occurring in 20% of U.S. population over the age of 70. Eighty-four percent of patients with radiographic evidence of compression fractures report severe associated back pain. Historically, VCFs have been primarily treated using vertebroplasty and kyphoplasty, which are techniques involving the injection of polymethylmethacrylate (PMMA) into the vertebral body through a transpedicular approach under fluoroscopy. Significant pain relief is achieved in 70% to 90% of patients treated using these procedures. However, more recent clinical evidence has shown that these procedures are extremely risky with significant complications amplified by an underlying condition of osteoporosis, including graft dislodgement and subsistence, loss of implant fixation, and junctional kyphosis. PMMA cement causes thermal necrosis of adjacent bone tissue due to its high polymerization temperature. Its lack of biodegradability coupled with its higher modulus of elasticity (i.e., stiffness) compared to cancellous bone has also led to fractures in adjacent vertebrae. Most concerning is the risk of extravasation, or cement leakage, which has occurred in up to 75% of all reported cases resulting in pulmonary embolisms occurring in up to 23% of patients tracked in published literature. It is therefore not surprising that the prevalence of these procedures decreased by more than 70% from their peak since this information has come to light. Unfortunately, however, this has left many patients in chronic pain without a viable treatment option. To address this issue RevBio, Inc., has developed Tetranite® (TN), a novel bone adhesive biomaterial that can bond bone fragments together and fill bone voids. Over time this proprietary material acts as a scaffold, allowing bone to grow through it and ultimately replace it with new, vital bone. Research indicates that the material is also osteopromotive and accelerates bone healing and remodeling in osteoporotic patients. TN’s proven injectability, low exothermal temperature, biodegradability, intrinsic mechanical strength, lack of toxicity, and cohesive properties allowing it to infiltrate cancellous bone, make it a good candidate for replacing PMMA to enable the treatment of patients with VCFs who suffer from chronic pain. As a result, this proposed research seeks to achieve the following Aims: Aim 1: Optimization of the Percutaneous Delivery of TN for VCF Procedures and Aim 2: Demonstration of the Safe and Effective Use of TN in a Large Animal Pilot Study. The results from this pilot animal study (Aim 2), complemented with surgeon validated simulated use cadaver testing (Aim 1A), will be used as the basis for developing a pivotal animal study to initiate regulatory discussions with the FDA. Long term, RevBio’s mission is to provide surgeons with a novel product that will enhance fixation and reduce complications associated with treating vertebral compression fractures in the elderly.