Cohort Study on Associations Between Purinergic Receptor SNPs and Osteoporosis Risk

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

Status

Completed

Phases

Unknown

Study type

Observational

Source

ClinicalTrials.gov

Registry ID

NCT00697983

Acronym

ATPBone

Enrollment

1000

Registered

2008-06-16

Start date

2008-08-31

Completion date

2010-12-31

Last updated

2011-04-20

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Osteoporosis

Keywords

Osteoporosis, ATP, Purinergic receptors, Bone mineral density, Single nucleotide polymorphism

Brief summary

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.

Interventions

None listed

Study design

Observational model

COHORT

Time perspective

CROSS_SECTIONAL

Eligibility

Sex/Gender

ALL

Age

50 Years to No maximum

Healthy volunteers

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).

Design outcomes

Primary

Measure	Time frame
Purinergic receptor SNPs	cross-sectional
BMD	cross-sectional

Secondary

Measure	Time frame
Biochemical markers of bone turnover	cross-sectional

Countries

Netherlands

Outcome results