Effect of Osteoporosis on Spine Fusion

骨质疏松症对脊柱融合的影响

• 批准号: 7673616
• 负责人: BRIAN CROCKETT COOLEY
• 金额: $ 7.58万
• 依托单位: MEDICAL COLLEGE OF WISCONSIN
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-01 至 2011-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7673616
• 关键词: Affect; Age; Autologous Transplantation; Bone Density; Bone Transplantation; Bone remodeling; Clinical Research; Congenital failure of fusion; Defect; Discrimination; Disease; Environment; Estrogens; Etiology; Experimental Designs; Extracellular Matrix Proteins; Failure; Fracture Healing; Future; Genes; Haplotypes; Healed; Investigation; Knockout Mice; Modeling; Mus; Mutation; Operative Surgical Procedures; Orthopedic Procedures; Osteoblasts; Osteoclasts; Osteonectin; Osteoporosis; Other Genetics; Outcome; Patients; Phenotype; Play; Predisposition; Recovery; Role; Site; Stem cells; Testing; Therapeutic; Time; Transplantation; Variant; Vertebral Bone; Vertebral column; abstracting; bone; design; healing; neglect; research study; response; success

DESCRIPTION (provided by applicant): Abstract Spine fusion surgery is associated with a significant failure rate (10-40%). A major potential cause is the presence of osteoporotic disease in the patient. The poor quality of osteoporotic bone can negatively impact upon healing after autografted spine fusion surgery. There are also multiple causes of osteoporosis; age and estrogen deficiency are leading candidates for the majority of patients, although gene haplotypes and other genetic variations may play roles. The following study is designed as a pilot investigation of the association of osteoporosis with poor outcome after spine fusion surgery. Two mouse lines which have highly characterized osteoporosis will be used together with a mouse spine fusion model developed by the PI, to determine causation of fusion failure with osteoporosis. One mouse line has greater numbers of osteoclasts due to a mutation in the SHIP gene, a modulator of osteoclast differentiation. The other mouse line has osteonectin deficiency, an extracellular matrix protein of bone that is necessary for normal bone integrity. Osteonectin-null mice have reduced numbers of both osteoblasts and osteoclasts, with a net reduction in bone density (i.e., osteoporosis). The study will test the hypothesis that osteoporosis is associated with a reduced response to spine fusion due to a defect in the bone graft or the vertebral bone or both. By using a cross-transplantation experimental design, effects of the bone graft can be separated from the recipient spine bone and circulating progenitor cells, thus permitting discrimination of osteoporotic influences on graft versus spine bone. Spine fusions will be evaluated at 1, 3, and 6 months to determine the time course for fusion under varying conditions of osteoporosis and the extent of remodeling of the fusion site. The results are expected to provide a better understanding of the influence of an osteoporotic state on response to spine fusion surgery. Future directions will include an in-depth investigation of the mechanistic aspects of fusion site bone remodeling under various conditions of osteoporosis, as well as investigations of therapeutic options for osteoporosis patients who require spine fusion surgery. Relevance Many patients with complications affecting the spine have osteoporosis as an additional component of their condition. The effect of underlying osteoporosis on the outcome of spine fusion surgery has been largely neglected in both experimental and clinical studies to date. Understanding how an osteoporotic predisposition influences spine fusion healing and remodeling is critical for developing better therapeutic options for these patients.

描述(由申请人提供)： 摘要脊柱融合术的失败率很高(10-40%)。一个主要的潜在原因是患者存在骨质疏松疾病。骨质疏松骨质量差会对自体脊柱融合手术后的愈合产生负面影响。骨质疏松也有多种原因；年龄和雌激素缺乏是大多数患者的主要候选因素，尽管基因单倍型和其他遗传变异可能起作用。以下研究旨在初步探讨脊柱融合术后骨质疏松症与不良预后的关系。两个具有高度骨质疏松特征的小鼠品系将与PI开发的小鼠脊柱融合模型一起使用，以确定融合失败与骨质疏松的原因。由于破骨细胞分化的调节剂SHIP基因的突变，一种小鼠系具有更多数量的破骨细胞。另一种小鼠缺乏骨连蛋白，这是一种骨骼的细胞外基质蛋白，是正常骨骼完整性所必需的。Osteonectin缺失的小鼠的成骨细胞和破骨细胞数量都减少了，骨密度也减少了(即骨质疏松)。这项研究将检验这一假设，即骨质疏松症与脊柱融合反应降低有关，这是由于植骨或椎骨或两者都有缺陷造成的。通过采用交叉移植实验设计，骨移植的效果可以从受体脊柱骨和循环中的祖细胞中分离出来，从而允许区分骨质疏松症对移植物和脊柱的影响。脊柱融合将在1、3和6个月时进行评估，以确定在不同的骨质疏松条件下融合的时间进程和融合部位重塑的程度。这一结果有望更好地了解骨质疏松状态对脊柱融合手术反应的影响。未来的方向将包括深入研究不同条件下骨质疏松症融合部位骨重建的机制，以及研究需要脊柱融合手术的骨质疏松症患者的治疗选择。许多有影响脊柱的并发症的患者将骨质疏松症作为其病情的附加组成部分。到目前为止，在实验和临床研究中，潜在的骨质疏松对脊柱融合手术结果的影响在很大程度上被忽略了。了解骨质疏松倾向如何影响脊柱融合、愈合和重塑，对于为这些患者开发更好的治疗方案至关重要。