osteoprotegerin and Hemorrhage

Elevated levels of osteoprotegerin, a secreted tumor necrosis factor-related molecule, might be associated with adverse outcomes in patients with coronary artery disease. We measured plasma osteoprotegerin concentrations on hospital admission, at discharge, and at 1 and 6 months after discharge in a predefined subset (n=5135) of patients with acute coronary syndromes in the PLATO (Platelet Inhibition and Patient Outcomes) trial.. The associations between osteoprotegerin and the composite end point of cardiovascular death, nonprocedural spontaneous myocardial infarction or stroke, and non-coronary artery bypass grafting major bleeding during 1 year of follow-up were assessed by Cox proportional hazards models. Event rates of the composite end point per increasing quartile groups at baseline were 5.2%, 7.5%, 9.2%, and 11.9%. A 50% increase in osteoprotegerin level was associated with a hazard ratio (HR) of 1.31 (95% confidence interval [CI], 1.21-1.42) for the composite end point but was not significant in adjusted analysis (ie, clinical characteristics and levels of C-reactive protein, troponin T, NT-proBNP [N-terminal pro-B-type natriuretic peptide], and growth differentiation factor-15). The corresponding rates of non-coronary artery bypass grafting major bleeding were 2.4%, 2.2%, 3.8%, and 7.2%, with an unadjusted HR of 1.52 (95% CI, 1.36-1.69), and a fully adjusted HR of 1.26 (95% CI, 1.09-1.46). The multivariable association between the osteoprotegerin concentrations and the primary end point after 1 month resulted in an HR of 1.09 (95% CI, 0.89-1.33); for major bleeding after 1 month, the HR was 1.33 (95% CI, 0.91-1.96).. In patients with acute coronary syndrome treated with dual antiplatelet therapy, osteoprotegerin was an independent marker of major bleeding but not of ischemic cardiovascular events. Thus, high osteoprotegerin levels may be useful in increasing awareness of increased bleeding risk in patients with acute coronary syndrome receiving antithrombotic therapy.. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00391872.

Topics: Acute Coronary Syndrome; Aged; Aspirin; Biomarkers; Clopidogrel; Drug Therapy, Combination; Female; Hemorrhage; Humans; Male; Middle Aged; Osteoprotegerin; Platelet Aggregation Inhibitors; Risk Assessment; Risk Factors; Ticagrelor; Time Factors; Treatment Outcome; Up-Regulation

Topics: Acute Disease; Adult; Bone Remodeling; Chronic Disease; Female; Hemorrhage; Humans; Male; Middle Aged; Osteoprotegerin; Periodontitis; RANK Ligand; Saliva; Up-Regulation; Young Adult

In multiple trauma patients an increased incidence of delayed healing and non-union has been observed. The exact mechanisms underlying this delayed fracture healing are still not fully understood.. 40 male C57BL/6N-mice underwent standardized midline laparotomy and pressure-controlled haemorrhage (TH) or implantation of catheters without blood loss (sham procedure). Animals were sacrificed 24h or 72 h later. Osteoprogenitor cells derived from bone marrow were isolated and differentiated into osteoblasts for 20 days and osteoclasts for 7 days. Osteoblast mineralization and osteoclast numbers were determined, and gene expression of Alpl, Bglap, Opg, Rankl was measured in osteoblast cell culture, as well as gene expression of Rank, Ctsk and Nfatc1 was determined in osteoclast cell culture. Furthermore, plasma Opg, Rankl and TRAP were measured.. Mineralization capacity of osteoblasts was unchanged after TH, but Alpl gene expression after 23 days was significantly decreased compared to sham. Osteoclast number of group TH 8 days was significantly decreased compared to sham. Furthermore, gene expression of Ctsk and Nfatc1 were increased in group TH 10 days compared to group TH 8 days. Plasma Opg concentration was significantly elevated and Rankl concentrations were significantly declined in TH groups compared to sham groups after 24h and 72 h.. TH results in a diminished osteoclast number after 8 days, whereas differentiation of osteoblasts seems to be unaffected. The reduction of osteoclast number seems to be mediated through the Rankl-Opg-signalling pathway. However, further studies in models including a fractured extremity with a longer observation period are needed to identify the relevance of the Rankl-Opg- pathway in delayed fracture healing after TH and to focus on possible therapeutic interventions.

Topics: Animals; Carrier Proteins; Cell Differentiation; Fracture Healing; Gene Expression Regulation; Glycoproteins; Hemorrhage; Male; Mice; Mice, Inbred C57BL; Osteoblasts; Osteoclasts; Osteoprotegerin; RANK Ligand

Patients with polycythemia vera (PV) have an increased risk for the development of thrombohemorrhagic complications. The pathogenesis of these complications is still unclear. An important role in vascular disease has recently been attributed to osteoprotegerin (OPG). It has been shown that various tissues of the cardiovascular system produce OPG, and there is growing evidence of an association between elevated serum OPG levels and cardiovascular morbidity. We evaluated if OPG was associated with an increased risk of venous thrombosis or bleeding complications in a cohort of 114 PV patients. The analysis consisted of a retrospective and a prospective part. In the retrospective univariate analysis, a one unit change in OPG caused the odds of venous thrombosis to increase by 40% (p=0.005) and the odds of bleeding to increase by 52% (p=0.001). Multivariate analysis only slightly attenuated the association to 33% (p=0.03) and 37% (p=0.013) for venous thrombosis and bleeding, respectively. OPG was also related to the development of the combined outcome of venous thrombosis and bleeding in the prospective analysis (log-rank-test: p=0.017). This is the first report that links the occurrence of venous thrombosis or bleeding to elevated OPG levels.

Topics: Adult; Aged; Aged, 80 and over; Analysis of Variance; Female; Glycoproteins; Hemorrhage; Humans; Male; Middle Aged; Osteoprotegerin; Polycythemia Vera; Prospective Studies; Receptors, Cytoplasmic and Nuclear; Receptors, Tumor Necrosis Factor; Retrospective Studies; Risk Factors; Venous Thrombosis