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

使用图像引导、经皮输送新型骨粘合剂改善老年患者椎体压缩性骨折的治疗

• 批准号: 10547209
• 负责人: Brian Hess
• 金额: $ 37.5万
• 依托单位: REVBIO, INC.
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-15 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10547209
• 关键词: Address; Adhesives; Age; Animal Model; Animals; Annual Reports; Back Pain; Biocompatible Materials; Blood gas; Bone Tissue; Bone remodeling; Cadaver; Case Study; Clinical; Complement; Compression Fracture; Compressive Strength; Coupled; Elasticity; Elderly; Embolism; Extravasation; Filler; Fluoroscopy; Fracture; Height; Histopathology; Human; Implant; Individual; Injectable; Injections; Kyphosis deformity of spine; Left; Literature; Lung; Mechanics; Medicare; Mission; Modulus; Monitor; Necrosis; Operative Surgical Procedures; Osteoporosis; Osteoporotic; Outcome Study; Pain; Patients; Persons; Pilot Projects; Polymethyl Methacrylate; Population; Prevalence; Procedures; Property; Publishing; Pulmonary Embolism; Reporting; Research; Risk; Surgeon; Techniques; Temperature; Testing; Time; Toxic effect; United States; Vertebral column; X-Ray Computed Tomography; aged; biomechanical test; bone; bone healing; chronic pain; cohesion; cost estimate; image guided; improved; in vivo; microCT; minimally invasive; novel; older patient; pain relief; polymerization; primary outcome; radiological imaging; sample fixation; scaffold; secondary outcome; sheep model; spine bone structure; substantia spongiosa; vertebra body

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.

项目摘要 美国每年大约发生 700,000 例椎体压缩性骨折 (“VCF”)，造成的损失 估计 2.5 亿美元的医疗保险相关费用。压缩性骨折最常见于 患有骨质疏松症的老年人，70 岁以上的美国人口中有 20% 患有骨质疏松症。百分之 84 有压缩性骨折影像学证据的患者报告有严重的相关背痛。 历史上，VCF 主要使用椎体成形术和椎体后凸成形术进行治疗，这些技术 涉及通过经椎弓根将聚甲基丙烯酸甲酯（PMMA）注射到椎体内 透视下的方法。使用这些药物治疗的患者中 70% 至 90% 的疼痛得到显着缓解 程序。然而，最近的临床证据表明，这些手术对于患者来说风险极大。 骨质疏松症的潜在病症会加剧严重的并发症，包括移植物移位和 生存、种植体固定丧失和交界性后凸。 PMMA水泥引起热坏死 由于其高聚合温度，邻近的骨组织。它缺乏生物降解性，加上它 与松质骨相比，较高的弹性模量（即刚度）也会导致邻近的骨折 椎骨。最令人担忧的是外渗或骨水泥渗漏的风险，这种情况发生在高达 75% 的 在已发表的文章中追踪的所有报告病例中，高达 23% 的患者发生肺栓塞 文学。因此，这些手术的流行率下降 70% 以上也就不足为奇了 自从这一信息曝光以来，他们的巅峰状态已经开始下降。然而不幸的是，这让许多患者陷入困境。 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，可以 将骨头碎片粘合在一起并填充骨头空隙。随着时间的推移，这种专有材料充当支架，允许 骨头穿过它生长并最终用新的、有活力的骨头取代它。研究表明，该材料是 还可以促进骨质疏松并加速骨质疏松患者的骨骼愈合和重塑。 TN已被证实 可注射性、低放热温度、生物可降解性、固有机械强度、无毒性，以及 粘性特性使其能够渗透松质骨，使其成为替代 PMMA 的良好候选者 能够治疗患有慢性疼痛的 VCF 患者。因此，本提议的研究 力求实现以下目标： 目标 1：优化 VCF 的 TN 经皮输送 程序和目标 2：在大型动物试点研究中证明 TN 的安全有效使用。 这项试点动物研究（目标 2）的结果，辅以外科医生验证的模拟使用尸体 测试（目标 1A）将用作开发关键动物研究的基础，以启动监管讨论 与 FDA 合作。从长远来看，RevBio 的使命是为外科医生提供一种增强固定的新型产品 并减少与治疗老年人椎体压缩性骨折相关的并发症。