The effect of thyroid hormone levels on osteoprotegerin/RANKL system and bone turnover in hashimoto thyroiditis

Thyroid hormones are necessary for normal skeletal growth and bone remodelling. Hypothyroidism causes slowing of bone turnover and an increase in the fracture risk by adversely affecting bone quality. A new body of evidence suggests that autoimmune disorders, as well, are associated with a disturbed bone turnover. Hashimoto?s thyroiditis is an autoimmune disorder in origin and the impact of autoimmunity and the resultant hypothyroidism on bone turnover in Hashimoto?s thyroiditis is not known. Osteoprotegerin(OPG)/Receptor activator nuclear kappa B ligand (RANKL) pathway is known to play a major role in bone remodelling and interleukin-6 (IL-6), which is an osteoclastogenic cytokine, may exert its inhibitory effect on bone formation indirectly by influencing the balance between OPG/RANKL. In this study, we assessed the levels of OPG, RANKL and IL-6 along with markers of bone formation as osteocalcin (OC), procollagen type I N propeptide (PINP), alkaline phosphatase (ALP) and markers of bone resorption as type 1 collagen C telopeptide (CTX) and tartrate resistant acid phosphatase isoform 5b (TRAcP 5b) in 30 hypothyroid and 30 euthyroid premenopausal Hashimoto?s thyroiditis patients and 20 healthy premenopausal controls. We found that TRAcP 5b, CTX and OC levels were lower and PINP was higher in the hypothyroid group compared to euthyroid Hashimoto patients and controls while serum ALP levels were similar among groups. OPG levels were higher and RANKL levels were lower in hypothyroid and euthyroid Hashimoto patients compared to controls. OPG was positively correlated with serum TSH. Hypothyroid Hashimoto patients had lower IL-6 levels compared to euthyroid Hashimoto and control groups. RANKL/OPG ratio was independently associated with the presence of Hashimoto thyroiditis and markers of bone turnover. In conclusion, bone turnover is adversely affected by hypothyroidism, potentially through OPG/RANKL pathway, in premenopausal patients with Hashimoto thyroiditis.