Purinergic Signalling in Human Osteoporosis: Evaluation of Variability in Purinergic Receptor Genes and Receptor Function
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 1,000
- 试验地点
- 1
- 主要终点
- Purinergic receptor SNPs
研究概览
简要总结
Background: Osteoporosis is a high-prevalence disease with a strong genetic component. Nucleotides, including ATP (adenosine 5'-triphosphate) and its purinergic receptors, play a role in bone physiology. Single nucleotide polymorphisms (SNPs) in the P2X7 receptor gene were recently found to be associated with fracture risk in a cohort of postmenopausal women.
Objective: To investigate associations between purinergic receptor SNPs and osteoporosis risk in humans. Genetic data from a fracture cohort in the Netherlands with high prevalence of osteoporosis will be analyzed. Furthermore, effects of aberrant purinergic receptor signalling on bone turnover markers will be assessed ex vivo.
Design: The cohort will include app. 1,000 fracture patients of 50 years and older, who will be recruited at the Maastricht University Medical Center during standard medical follow-up after a clinical fracture. The standard medical follow-up includes assessment of bone mineral density (BMD) by Dual-Energy X-ray Absorptiometry (DXA), if necessary followed by medication for osteoporosis. Prior to medication, blood samples will be collected from fracture patients to be genotyped for purinergic receptor SNPs and analyzed for biochemical markers of bone turnover. Systemic correlates of osteoporosis will be compared between osteoporotic subjects (i.e. low BMD) and non-osteoporotic controls (i.e. normal to high BMD). Subsequently, whole blood assays in patient subgroups (n=20 per subgroup), based on BMD and purinergic receptor SNPs, will be performed to evaluate ex vivo effects of ATP and related nucleotides bone markers.
Study population: Patients of 50 years and older attending an outpatient osteoporosis clinic at the Maastricht University Medical Center for standard medical follow-up after a clinical, non-pathological fracture.
Primary outcome parameters: BMD and purinergic receptor SNPs.
Secondary outcome parameters: Bone markers.
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
- 50 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 50 years and older;
- •Clinical fracture;
- •Attending osteoporosis outpatient clinic for standard medical care.
排除标准
- •Disease of bone metabolism (e.g. bone tumours, hyperparathyroidism);
- •Unwillingness to donate blood for DNA analyses;
- •Failure of bone densitometry (DXA-scan).
结局指标
主要结局
Purinergic receptor SNPs
时间窗: cross-sectional
BMD
时间窗: cross-sectional
次要结局
- Biochemical markers of bone turnover(cross-sectional)