Clinical trial NCT00697983: Cohort Study on Associations Between Purinergic Receptor SNPs and Osteoporosis Risk
Official title: Purinergic Signalling in Human Osteoporosis: Evaluation of Variability in Purinergic Receptor Genes and Receptor Function
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Osteoporosis
Keywords: Osteoporosis
ATP
Purinergic receptors
Bone mineral density
Single nucleotide polymorphism
Lead sponsor: Maastricht University Medical Center
Sponsor class: OTHER
Collaborators: name: Copenhagen University Hospital, Research Center for Aging and Osteoporosis
name: European Commission
First posted: 2008-06-16
Enrollment: 1000
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Fracture patients of 50 years and older attending an osteoporosis outpatient clinic at the Maastricht University Medical Center

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.


Eligibility 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).

Primary outcomes:
measure: Purinergic receptor SNPs
timeFrame: cross-sectional
measure: BMD
timeFrame: cross-sectional
Secondary outcomes:
measure: Biochemical markers of bone turnover
timeFrame: cross-sectional
Other outcomes:
Locations:
city: Maastricht
country: Netherlands
facility: Maastricht University Medical Center
state: Limburg
Study officials:
affiliation: Maastricht University, Dept of Epidemiology
name: Pieter C Dagnelie, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: Ohlendorff SD, Tofteng CL, Jensen JE, Petersen S, Civitelli R, Fenger M, Abrahamsen B, Hermann AP, Eiken P, Jorgensen 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. doi: 10.1097/FPC.0b013e3280951625.
citation: 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. doi: 10.1016/S0165-6147(03)00123-8.
citation: 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. doi: 10.1016/j.pharmthera.2005.04.013. Epub 2006 Jun 19.
citation: 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. doi: 10.1016/j.bbrc.2006.07.177. Epub 2006 Aug 4.
citation: 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.