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

项目摘要 在美国每年发生大约700，000例椎骨压缩性骨折（“VCF”）， 医疗保险相关费用估计为2.5亿美元。压缩性骨折最常见于 患有骨质疏松症的老年人，在70岁以上的美国人口中占20%。百分之八十四 的有影像学证据的压缩性骨折患者报告严重的相关背痛。 历史上，VCF主要采用椎体成形术和椎体后凸成形术治疗， 包括将聚甲基丙烯酸甲酯（PMMA）通过经椎弓根注入椎体 透视下入路。使用这些药物治疗的患者中，70%至90%的患者疼痛明显缓解。 程序.然而，最近的临床证据表明，这些程序是非常危险的， 骨质疏松症的基础疾病加重了严重的并发症，包括移植物移位， 生存、植入物固定丢失和交界性脊柱后凸。PMMA骨水泥导致 由于其高聚合温度，邻近骨组织。它缺乏生物降解性， 较高的弹性模量（即，与松质骨相比， 椎骨最令人担忧的是外渗或骨水泥泄漏的风险， 在已发表的文献中，所有报告的导致肺栓塞的病例在跟踪的患者中发生率高达23%。 文学因此，这些程序的流行率下降了70%以上并不奇怪 自从这一消息曝光以来，他们的峰值。然而，不幸的是，这使得许多患者 没有可行的治疗方案的慢性疼痛。 为了解决这个问题，RevBio，Inc.，开发了Tetranite®（TN），一种新型骨粘合生物材料， 将骨碎片粘合在一起并填充骨空隙。随着时间的推移，这种专有材料充当支架， 骨骼在其中生长并最终被新的有活力的骨骼取代。研究表明，该材料 也是骨促进剂并加速骨质疏松患者的骨愈合和重塑。经证实， 可注射性、低暴露温度、生物降解性、固有机械强度、无毒性，以及 内聚特性使其能够渗透松质骨，使其成为替代PMMA的良好候选材料， 能够治疗患有慢性疼痛的VCF患者。因此，本研究提出 旨在实现以下目标：目标1：优化经皮输送TN治疗VCF 程序和目标2：在大型动物中试研究中证明TN的安全有效使用。 该初步动物研究（目标2）的结果，以及外科医生确认的模拟使用尸体 试验（目标1A），将用作开展关键动物研究的基础，以启动监管讨论 和食品药物管理局从长远来看，RevBio的使命是为外科医生提供一种新的产品， 并减少与治疗老年人椎体压缩性骨折相关的并发症。

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.