Alteration of plasma concentrations of OPG before and after levothyroxine replacement therapy in hypothyroid patients

Objective: Osteoprotegerin (OPG) is a newly identified inhibitor of bone resorption. Recent studies indicate that OPG also acts as an important regulatory molecule in the vasculature. Hypothyroidism is associated with increased morbidity from cardiovascular disease. More recently, one study showed that plasma OPG increases significantly, and decreases markedly with levothyroxine (L-T-4) replacement therapy in patients with overt hypothyroidism (oHT). The purpose of this study was to investigate the alteration of plasma OPG concentrations before and after L-T-4 replacement therapy, and its association with endothelium-dependent arterial dilation in patients with oHT and subclinical hypothyroidism (sHT). Materials and Methods: The study subjects included 20 women with oHT, 20 women with sHT, and 20 healthy women. All patients were then given L-T-4 therapy individually to maintain all serum free T-3 (FT3), free T-4 (FT4), and TSH near or within the respective normal ranges. Plasma OPG concentration was measured in duplicate by a sandwich ELISA method. Results: Plasma OPG levels in oHT and sHT patients before treatment were 3.13 +/- 0.27 and 2.95 +/- 0.24 ng/l, respectively, which were significantly higher than that in controls (2.42 +/- 0.26 ng/l) (p = 0.000). In multivariate analysis, OPG was significantly associated with TSH (r = 0.306, p < 0.05) and endothelium-dependent arterial dilation (r = -0.675, p < 0.01) at baseline. After normalization of thyroid function, OPG levels in both groups decreased markedly (2.53 +/- 0.28, 2.54 +/- 0.21 ng/l) (p = 0.000), and were very close to that in controls. The absolute changes in OPG showed significant positive correlation with the changes in TSH (p < 0.05) and negative correlation with the changes in endothelium-dependent arterial dilation (p < 0.01), and no significant correlation with other parameters in hypothyroid patients during the course of treatment. Conclusion: The plasma OPG levels were significantly increased from hypothyroid patients, and were close to those of control subjects after normalization of thyroid function, indicating that OPG acts as an important regulatory molecule in the vasculature and, particularly, that it may be involved in the development of vascular dysfunction in hypothyroid patients.