ATPBone: Cohort Study on Associations Between Purinergic Receptor SNPs and Osteoporosis Risk
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Fracture cohort 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). |
Outcome Measures
Primary Outcome Measures
- Purinergic receptor SNPs [cross-sectional]
- BMD [cross-sectional]
Secondary Outcome Measures
- Biochemical markers of bone turnover [cross-sectional]
Eligibility Criteria
Criteria
Inclusion Criteria:
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Age 50 years and older;
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Clinical fracture;
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Attending osteoporosis outpatient clinic for standard medical care.
Exclusion Criteria:
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Disease of bone metabolism (e.g. bone tumours, hyperparathyroidism);
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Unwillingness to donate blood for DNA analyses;
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Failure of bone densitometry (DXA-scan).
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Maastricht University Medical Center | Maastricht | Limburg | Netherlands |
Sponsors and Collaborators
- Maastricht University Medical Center
- Copenhagen University Hospital, Research Center for Aging and Osteoporosis
- European Commission
Investigators
- Principal Investigator: Pieter C Dagnelie, PhD, Maastricht University, Dept of Epidemiology
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
- Bours MJ, Swennen EL, Di Virgilio F, Cronstein BN, Dagnelie PC. Adenosine 5'-triphosphate and adenosine as endogenous signaling molecules in immunity and inflammation. Pharmacol Ther. 2006 Nov;112(2):358-404. Epub 2006 Jun 19. Review.
- Bours MJL, Wesselius A en Dagnelie PC. Adenosinetrifosfaat (ATP), purinerge receptoren en botremodellering. Nieuwe perspectieven voor behandeling van osteoporose? Ned Tijdschr Calcium Botstofwisseling 2009; 7(3):71-4.
- Hoebertz A, Arnett TR, Burnstock G. Regulation of bone resorption and formation by purines and pyrimidines. Trends Pharmacol Sci. 2003 Jun;24(6):290-7. Review.
- Ohlendorff SD, Tofteng CL, Jensen JE, Petersen S, Civitelli R, Fenger M, Abrahamsen B, Hermann AP, Eiken P, Jørgensen NR. Single nucleotide polymorphisms in the P2X7 gene are associated to fracture risk and to effect of estrogen treatment. Pharmacogenet Genomics. 2007 Jul;17(7):555-67. Erratum in: Pharmacogenet Genomics. 2007 Sep;17(9):787. Jrgensen, Niklas R [corrected to Jørgensen, Niklas R].
- Swennen EL, Bast A, Dagnelie PC. Purinergic receptors involved in the immunomodulatory effects of ATP in human blood. Biochem Biophys Res Commun. 2006 Sep 29;348(3):1194-9. Epub 2006 Aug 4.
- van Helden S, van Geel AC, Geusens PP, Kessels A, Nieuwenhuijzen Kruseman AC, Brink PR. Bone and fall-related fracture risks in women and men with a recent clinical fracture. J Bone Joint Surg Am. 2008 Feb;90(2):241-8. doi: 10.2106/JBJS.G.00150.
- MEC 08-3-029
- EU FP7, grant no. 202231