Cohort Study on Associations Between Purinergic Receptor SNPs and Osteoporosis Risk

Study Overview
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Brief Summary
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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.

Official Title
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Purinergic Signalling in Human Osteoporosis: Evaluation of Variability in Purinergic Receptor Genes and Receptor Function

Conditions
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Osteoporosis

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 50 years and older; Clinical fracture; Attending osteoporosis outpatient clinic for standard medical care. Exclusion Criteria: Disease of bone metabolism (e.g. bone tumours, hyperparathyroidism); Unwillingness to donate blood for DNA analyses; Failure of bone densitometry (DXA-scan).

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Fracture cohort<br>Patients of 50 years and above with a clinical, non-pathological fracture, who attend an osteoporosis outpatient clinic at the Maastricht University Medical Center for standard medical care (including bone densitometry by DXA-scan). | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Purinergic receptor SNPs |  | cross-sectional | 
| BMD |  | cross-sectional | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Biochemical markers of bone turnover |  | cross-sectional | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Osteoporosis, ATP, Purinergic receptors, Bone mineral density, Single nucleotide polymorphism