Bone remodelling markers and serum cytokines in patients with hyperthyroidism

This study was designed in order to evaluate bone turnover with bone formation and resorption markers in hyperthyroidism and its possible relationship with serum cytokines interleukin 6 (IL-6) and tumour necrosis-alpha (TNF-alpha), levels of thyroid hormones and thyroid autoantibodies.

Twenty-six hyperthyroid patients including nine with Graves' disease, 14 with toxic multi-nodular disease and three toxic adenoma were studied. Twenty normal subjects served as the control group.

Serum calcium, phosphorus, total and bone-specific alkaline phosphatase, procollagen type 1-C peptide (PICP), osteocalcin, IL-6 and TNF-alpha measurements were performed and deoxypyridinoline (free DPD), calcium, phosphorus and creatinine levels were measured in fasting morning urine specimens of all hyperthyroid patients and all controls. Also, serum total and free T3 and T4 and TSH were analysed and thyroid antiperoxidase and antithyroglobulin antibodies were determined in sera of hyperthyroid patients. Patients with hyperthyroidism received propylthiouracil treatment until the achievement of euthyroidism and then serum cytokine levels were remeasured.

Mean serum values of osteocalcin, total and bone-specific alkaline phosphatase were all significantly higher in hyperthyroid patients than in normal controls. PICP levels were not significantly different between these two groups. Urinary deoxypyridinoline levels were markedly elevated in hyperthyroid patients compared to the control group. There was a significant positive correlation between urinary free DPD levels and serum free T3, free T4 and T4 levels. Serum free T4 levels also correlated with urinary calcium levels. Serum IL-6 values were significantly higher in hyperthyroid patients compared to control group. TNF-alpha levels were slightly lower in patients with hyperthyroidism. No significant correlation was found between bone remodelling markers and serum cytokines. Serum Il-6 levels were correlated positively with age. After the treatment period both IL-6 and TNF-alpha returned to levels comparable with euthyroid controls.

Bone turnover is increased in favour of resorption and the rate of resorption is associated with the levels of thyroid hormones in hyperthyroidism. The increase in the levels of serum IL-6 in hyperthyroidism is not related directly with bone resorption seen in hyperthyroidism.