Cohort Study on Associations Between Purinergic Receptor SNPs and Osteoporosis Risk - Full Text View

Sponsors and Collaborators:	Maastricht University Medical Center Copenhagen Trial Unit, Center for Clinical Intervention Research European Commission
Information provided by:	Maastricht University Medical Center
ClinicalTrials.gov Identifier:	NCT00697983

Purpose

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 in the University Hospital Maastricht 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 University Hospital Maastricht 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
Osteoporosis

MedlinePlus related topics: Fractures Minerals Osteoporosis

U.S. FDA Resources

Study Type:	Observational
Study Design:	Cohort, Cross-Sectional
Official Title:	Purinergic Signalling in Human Osteoporosis: Evaluation of Variability in Purinergic Receptor Genes and Receptor Function

Further study details as provided by Maastricht University Medical Center:

Primary Outcome Measures:

Purinergic receptor SNPs [ Time Frame: cross-sectional ] [ Designated as safety issue: No ]
BMD [ Time Frame: cross-sectional ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Biochemical markers of bone turnover [ Time Frame: cross-sectional ] [ Designated as safety issue: No ]

Biospecimen Retention: Samples With DNA

Biospecimen Description:

Whole blood, serum, plasma

Estimated Enrollment:	1000
Study Start Date:	July 2008
Estimated Study Completion Date:	June 2011
Estimated Primary Completion Date:	December 2009 (Final data collection date for primary outcome measure)

Groups/Cohorts
Fracture cohort Patients of 50 years and above with a clinical, non-pathological fracture, who attend an osteoporosis outpatient clinic at the University Hospital Maastricht for standard medical care (including bone densitometry by DXA-scan).

Eligibility

Ages Eligible for Study:	50 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No
Sampling Method:	Non-Probability Sample

Study Population

Fracture patients of 50 years and older attending an osteoporosis outpatient clinic at the University Hospital Maastricht

Criteria

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).

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00697983

Contacts

Contact: Pieter C. Dagnelie, PhD	314-3388-2393	Dagnelie@epid.unimaas.nl
Contact: Martijn J.L. Bours, PhD	314-3388-2903	M.Bours@epid.unimaas.nl

Locations

Netherlands, Limburg
University Hospital Maastricht
Maastricht, Limburg, Netherlands

Sponsors and Collaborators

Maastricht University Medical Center

Copenhagen Trial Unit, Center for Clinical Intervention Research

European Commission

Investigators

Principal Investigator:

Pieter C. Dagnelie, PhD

Maastricht University, Dept of Epidemiology

More Information

European Nucleotides and Bone Consortium This link exits the ClinicalTrials.gov site

European Commission Research, Seventh Framework Programme This link exits the ClinicalTrials.gov site

University Hospital Maastricht This link exits the ClinicalTrials.gov site

Maastricht University, Dept of Epidemiology This link exits the ClinicalTrials.gov site

Publications:

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.

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 Jorgensen, Niklas R].

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.

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.

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.

Responsible Party:	Maastricht University ( dr. ir. P.C. Dagnelie )
Study ID Numbers:	MEC 08-3-029, EU FP7, grant no. 202231
Study First Received:	June 11, 2008
Last Updated:	June 13, 2008
ClinicalTrials.gov Identifier:	NCT00697983
Health Authority:	Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Maastricht University Medical Center:

Osteoporosis
ATP
Purinergic receptors
Bone mineral density
Single nucleotide polymorphism

Study placed in the following topic categories:

Musculoskeletal Diseases
Osteoporosis
Bone Diseases, Metabolic
Bone Diseases

ClinicalTrials.gov processed this record on January 15, 2009