Graz Osteoprotegerin as a Risk Factor (GORF) Study

Graz Osteoprotegerin as a Risk Factor (GORF) Study: THE ROLE of OSTEOPROTEGERIN (OPG) and the RECEPTOR ACTIVATOR OF NUCLEAR FACTOR-Kb LIGAND (RANKL) IN PATIENTS REQUIRING SURGERY FOR CORONARY HEART DISEASE

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.

Study Overview

• Status: Unknown
• Conditions: Prevalent OPG and RANKL Excession in Patients With CAD

• Study Type: Observational
• Enrollment (Anticipated): 150

Contacts and Locations

Study Locations

• Austria
  • Graz, Austria, 8036
    • Recruiting
    • Medical University of Graz
    • Contact: Doris Wagner, MD; Phone Number: 80651 0043 316 385; Email: doris.wagner@medunigraz.at
    • Contact: Daniela Malliga, MD; Phone Number: 80681 0043 316 385; Email: daniela-eugenia.martin@medunigraz.at

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

• Sampling Method: Non-Probability Sample

Study Population

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.

Description

Inclusion Criteria:

• 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:

• 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 Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
CAD Patients; Patients suffering from CAD requiring coronary artery bypass grafting
Control Patients; Patients without CAD

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
OSTEOPROTEGERIN (OPG)	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.	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.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
RANKL	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.	At baseline. The participants will be followed for the duration of hospital stay, an expected average of 10 days.

Collaborators and Investigators

• Sponsor: Medical University of Graz
• Collaborators: Medical University of Vienna
• Investigators: Principal Investigator: Daniela Malliga, MD, Medical University of Graz, Department of Surgery, Division for Cardiac Surgery; Study Director: Astrid Fahrleitner-Pammer, Prof., Medical University of Graz, Department of Internal Medicine, Division for Endocrinology and Metabolism; Study Chair: Doris Wagner, MD, Medical University of Graz, Department of Surgery, Division for Transplantation

Study record dates

Study Major Dates

• Study Start: July 1, 2010
• Primary Completion (Anticipated): July 1, 2012
• Study Completion (Anticipated): September 1, 2012

Study Registration Dates

• First Submitted: April 4, 2012
• First Submitted That Met QC Criteria: April 9, 2012
• First Posted (Estimate): April 10, 2012

Study Record Updates

• Last Update Posted (Estimate): April 10, 2012
• Last Update Submitted That Met QC Criteria: April 9, 2012
• Last Verified: April 1, 2012

More Information

Terms related to this study

• Keywords: Coronary artery disease; OPG; RANKL; bone disease
• Other Study ID Numbers: GORF 2.0