Changes of plasma concentration of osteoprotegerin and its association with endothelial dysfunction before and after hypouricemic therapy in patients with hyperuricemia.

ABSTRACT

OBJECTIVE: Osteoprotegerin (OPG) is a secreted glycoprotein in the regulation of bone turnover. Recently, many studies showed that OPG acts as an important regulatory molecule in the vascular systems. Our objective was to examine the plasma OPG levels alteration and its association with endothelial function before and after hypouricemic therapy in patients with hyperuricemia. METHODS: Thirty patients (28 males and 2 females, serum uric acid > 7.0 mg/dl) with hyperuricemia were selected. Thirty healthy individuals (28 males and 2 females) with normal serum uric acid were also selected as control. Patients were administered with hypouricemic therapy for 6 months. Plasma OPG concentration was measured in duplicate using a sandwich ELISA and high-resolution ultrasound was used to measure brachial artery diameter at rest, after reactive hyperemia and after sublingual glyceryltrinitrate. RESULTS: Plasma OPG levels in patients with hyperuricemia before hypouricemic therapy was significantly higher than those in controls (3.39 ± 0.25 vs. 2.05 ± 0.74 ng/L, p < 0.01). After hypouricemic therapy, OPG levels decreased markedly (2.54 ± 0.38 ng/L, p < 0.01). Flow-mediated dilation (FMD) in patients with hyperuricemia was 3.07 ± 1. 23%, which was significantly lower than that in control subjects (4.62 ± 0.69%, p < 0.01), and it improved significantly after hypouricemic therapy (3.91 ± 1.37%, p < 0.01). The absolute changes in OPG showed a significant positive correlation with the changes in serum uric acid (p < 0.05) and negative correlation with the changes in FMD (p < 0.01) in patients with hyperuricemia during the course of hypouricemic therapy. CONCLUSION: The current study demonstrates that plasma OPG levels increased significantly in patients with hyperuricemia and decreased significantly after hypouricemic therapy, and are correlated with FMD. These findings support the growing concept that elevated plasma OPG levels may be involved with the development of endothelial dysfunction in patients with hyperuricemia.