Graz Osteoprotegerin as a Risk Factor (GORF) Study
- Conditions
- Prevalent OPG and RANKL Excession in Patients With CAD
- Registration Number
- NCT01574963
- Lead Sponsor
- Medical University of Graz
- Brief Summary
Osteoprotegerin (OPG) is membrane bound in the immune system but can also be produced and secreted almost everywhere in the organism, so that it is mainly available in soluble form. So far, the OPG/RANKL/RANK system has been most intensively studied in bone. The binding of RANKL on its receptor RANK, which is expressed by osteoclasts, activates a number of osteoclastic cell functions. OPG also has a key function in the vascular system. Patients with coronary heart disease (CAD) have elevated OPG serum levels, probably as a sign of ischemic or inflammatory endothelial damage. Elevated OPG levels were also found in patients with advanced heart failure, whereby OPG correlated with pro BNP (brain natriuretic peptide) and was a predictor for cardiovascular morbidity and mortality.
Our prospective cohort study will include 150 men (75 patients requiring surgery for CAD and a control group without coronary heart disease). The primary endpoints are the differences between the two groups in serum levels of OPG and RANKL, markers of bone metabolism (osteocalcin \[OC\], crosslaps \[CTX\], tartrate resistant acid phosphatase (TRAP5b), 25(OH) vitamin D \[Vit D\], 1.25(OH) vitamin D, parathormone \[iPTH\], endocrine parameters related to vascular damage (e.g. aldosterone, renin and cortisol) and bone mineral density. Metabolomic based biomarkers will be evaluated to explore the mechanisms behind OPG-RANKL linked CVD damage. In the patients further studies of the mRNA expression of OPG, RANKL, TRAP5b, arginine:glycine amidinotransferase (AGAT) and osteocalcin in bone (sternum sliver) and vascular wall (aorta, internal thoracic artery and the great saphenous vein) will be performed.
A further study endpoint is the analysis of a causal coincidence between osteoporosis and CAD and the discrimination of possible key factors in the two entities. These will be determined by the correlation between the above-mentioned markers in serum and the expression in different vessels and in bone tissue.
In addition to analysis of the degree of vascular sclerosis, the mineral content of the bone will also be analyzed in a subpopulation with quantitative backscattered electron imaging (qBEI) related to the degree of vascular sclerosis and bone mineral density. The ultimate goal of the analysis is the discrimination of the most sensitive predictive marker(s) for diagnosis and outcome of patients with CAD for the purpose of early diagnosis and primary prevention of the disease.
CAD and osteoporosis are increasingly prevalent diseases that overlap. In both entities, OPG plays a role not only in pathogenesis but also as an outcome predictor. We aim to study the relevance of OPG concentration in serum but also in the vessel wall and the bone.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- Male
- Target Recruitment
- 150
- Male patients above 40 years of age presenting with symptomatic CAD and scheduled for a coronary artery bypass graft (CABG) are eligible for the study. The control group includes male patients scheduled for elective surgery other than cardiac procedures.
- Exclusion criteria are a second indication for heart surgery, chronic renal disease with a glomerular filtration rate < 30ml/min, advanced liver disease (AST, ALT, GGT > 3fold upper limit of normal), history of malignancy within the last 5 years and ongoing osteoprotective treatment.
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method OSTEOPROTEGERIN (OPG) Baseline at time 0 (at the beginning of the study). The participants will be followed for the duration of hospital stay, an expected average of 10 days. The primary endpoints are the differences between the two groups in serum levels of OPG and RANKL, markers of bone metabolism (osteocalcin \[OC\], crosslaps \[CTX\], tartrate resistant acid phosphatase (TRAP5b), 25(OH) vitamin D \[Vit D\], 1.25(OH) vitamin D, parathormone \[iPTH\], endocrine parameters related to vascular damage (e.g. aldosterone, renin and cortisol) and bone mineral density.
- Secondary Outcome Measures
Name Time Method RANKL At baseline. The participants will be followed for the duration of hospital stay, an expected average of 10 days. The primary endpoints are the differences between the two groups in serum levels of OPG and RANKL, markers of bone metabolism (osteocalcin \[OC\], crosslaps \[CTX\], tartrate resistant acid phosphatase (TRAP5b), 25(OH) vitamin D \[Vit D\], 1.25(OH) vitamin D, parathormone \[iPTH\], endocrine parameters related to vascular damage (e.g. aldosterone, renin and cortisol) and bone mineral density.
Trial Locations
- Locations (1)
Medical University of Graz
🇦🇹Graz, Austria