Receptor activator of nuclear factor kappaB ligand and osteoprotegerin in men with thyroid cancer.

Background: Suppressive thyroid hormone therapy is generally a lifelong treatment for patients with differentiated thyroid cancer (DTC). However, long-standing thyrotropin (TSH) suppression is a risk factor for osteoporosis. Osteoprotegerin (OPG) and receptor activator of nuclear factor kappaB ligand (RANKL) are central regulators of bone turnover. The aim was to analyze the effects of a suppressive thyroid hormone therapy in males with DTC on the OPG/RANKL system and on bone metabolism.

Patients And Methods: The OPG and soluble RANKL (sRANKL) were determined in 40 men (mean age, 53.2 years) with DTC on suppressive thyroid hormone therapy (TSH; 0.053 +/- 0.037 mU L(-1), duration 5.7 +/- 4.4 years) and 120 healthy controls matched for age. The markers of bone metabolism were C-terminal telopeptide of type I collagen in serum (sCTx) and osteocalcin (OC).

Results: The control group had OPG values (mean +/- SD) of 1.9 +/- 1.0 pmol L(-1) and sRANKL values of 0.40 +/- 0.62 pmol L(-1). In patients with DTC, results for OPG were 3.03 +/- 1.04 pmol L(-1) (P < 0.05) and for sRANKL were 0.13 +/- 0.16 pmol L(-1) (P < 0.05). The control group presented values for sCTx of 2669 +/- 1132 pmol L(-1) and for OC of 17.89 +/- 6.5 ng mL(-1). Patients with DTC on suppressive thyroid hormone therapy had increased sCTx values of 3810 +/- 2020 pmol L(-1) (P = 0.03) but comparable OC values of 19.21 +/- 7.67 ng mL(-1) (NS).

Conclusions: Suppressive thyroid hormone therapy in men with DTC increased bone degradation and induced significant changes in the OPG/RANKL system. These changes include, besides the risk of osteoporosis, possible negative effects on the vascular function and an increased risk of cardiovascular disease.