Effect of Osteoporosis on Spine Fusion

骨质疏松症对脊柱融合的影响

• 批准号: 7821313
• 负责人: BRIAN CROCKETT COOLEY
• 金额: $ 7.5万
• 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/7821313
• 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）： 摘要脊柱融合手术的失败率很高（10-40%）。一个主要的潜在原因是患者体内存在类风湿性疾病。自体植骨融合术后，不良的骨质疏松会对愈合产生负面影响。骨质疏松症也有多种原因;年龄和雌激素缺乏是大多数患者的主要候选人，尽管基因单倍型和其他遗传变异可能起作用。以下研究旨在初步调查骨质疏松症与脊柱融合术后不良结局之间的关系。两个具有高度特征性骨质疏松症的小鼠品系将与PI开发的小鼠脊柱融合模型一起使用，以确定骨质疏松症导致融合失败的原因。一种小鼠品系由于SHIP基因突变而具有更多数量的破骨细胞，SHIP基因是破骨细胞分化的调节因子。另一个小鼠品系有骨粘连蛋白缺乏症，骨粘连蛋白是一种骨细胞外基质蛋白，是正常骨完整性所必需的。无骨连接素的小鼠具有减少的成骨细胞和破骨细胞的数量，骨密度净减少（即，骨质疏松症）。本研究将检验骨质疏松症与由于骨移植物或椎骨或两者缺陷导致的脊柱融合反应降低相关的假设。通过使用交叉移植实验设计，可以将骨移植物的作用与受体脊柱骨和循环祖细胞分离，从而允许区分移植物对脊柱骨的再生影响。将在1、3和6个月时评价脊柱融合，以确定不同骨质疏松症条件下的融合时间进程和融合部位的重塑程度。这些结果有望更好地理解脊柱融合术对患者预后的影响。未来的研究方向将包括对各种骨质疏松症条件下融合部位骨重塑的机制方面进行深入研究，以及对需要脊柱融合手术的骨质疏松症患者的治疗选择进行研究。相关性许多患有影响脊柱的并发症的患者都有骨质疏松症作为其病情的额外组成部分。迄今为止，在实验和临床研究中，潜在的骨质疏松症对脊柱融合手术结果的影响在很大程度上被忽视了。了解脊椎病倾向如何影响脊柱融合愈合和重建对于为这些患者开发更好的治疗方案至关重要。