Identification and Characterization of Genetic Regulators of Bone Health That Are Unique to Vertebral Bone.
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 550
- 试验地点
- 1
- 主要终点
- Gene and transcript quantification
研究概览
简要总结
Osteoporosis is an age related disease in which a person's bone slowly becomes weaker with time. The bones may become so weak that they break easily such as a fall from standing height. The most commonly broke bones in osteoporosis are those of the hip, the spine or the wrist. Osteoporosis runs in families meaning that genetic differences explain why some people break bones in old age and other do not. Genetic studies have been done that show the the genes associated with spine (vertebral) fractures (broken bones) and hip fractures are different, suggesting that osteoporosis of the spine is not the exact same disease as osteoporosis of the hip. Genetic studies tell us what part of the genome (i.e. genes) are associated with a disease, but do not tell us how these genes act biologically to cause that disease. In this study, we seek to determine how the genes uniquely associated with spine osteoporosis behave in normal and aged bone, to determine how they interact with each other as a team to impact spine bone. In this study, we will measure gene activity (so called gene expression) in bone samples taken from people undergoing major spine deformity surgery. We will using genetic data from these patients to determine how gene activity is controlled in bone and how that relates to measures of bone health such as bone mineral density data. The results of this study will provide critical data regarding how osteoporosis of the spine happens, and these data will be used to find better and safer treatments to prevent bone fractures of the spine that happen with age.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Cross Sectional
入排标准
- 年龄范围
- 18 Years 至 85 Years(Adult, Older Adult)
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Men and women between the ages of 18 and 85 undergoing a multi-level spinal fusion (i.e. a T10 (or higher) fusion to the pelvis) -OR- a 3 column osteotomy with a corpectomy from for short segment surgeries -OR- a vertebral column resection (VCR) involving a corpectomy -OR- any deformity correction surgery wherein the attending surgeon determines that a large amount of bone containing trabecular elements will be removed and discarded.
- •Willing and able to provide informed consent
排除标准
- •End stage renal disease.
- •Any history of cancer.
- •Reliance on a wheelchair for 70% or greater of their mobility for longer than 12 months.
- •Quadra or paraplegia due to spinal cord injury.
- •Current use of epilepsy medications.
- •Confirmed Marfans, osteogenesis imperfecta or other genetic syndrome known to impact bone formation (Guacher's, Vit D independent rickets, etc).
- •Current glucocorticoid use lasting longer than 3 months, or greater than 6 months lifetime use.
- •Current or suspected current infection associated with orthopedic hardware.
- •HIV or Hep C positive and or currently on anti-viral medications.
- •History of gastric bypass surgery and or weigh loss exceeding 100 pounds.
- •Primary or secondary hyperparathyroidism.
- •Paget's disease
结局指标
主要结局
Gene and transcript quantification
时间窗: Baseline
The abundances (in transcripts per million, TPM) of all known transcripts will be quantified in each bone sample via next generation RNA-sequencing.
Genotypes
时间窗: Baseline
Low coverage whole genome sequence data will be obtained from all participants and the yielded outcome will be high quality genotypes for millions of single nucleotide polymorphism (SNPs) across the patient's genome. As this is low coverage genotyping, the coverage rate will be between 1 and 0.4X representation for each spot in the genome per patients, so the data will be imputed to ensure coverage to 1X for all patients. Each patient will be genotyped and therefore, data on a per participant level will be yielded.
次要结局
- Co-localization(Baseline)
- Expression-phenotype correlation(Baseline)
- Co-expression Network(Baseline)
- Expression quantitative trait loci (eQTL)(Baseline)
