Endocrine Abstracts

The association between thyrotoxicosis and osteoporosis has been recognised for over 100 years. Clinical studies in hyperthyroidism reveal a state of high bone turnover with activation of both osteoclasts and osteoblasts.

A longitudinal clinical study was performed in patients with thyrotoxicosis to study changes in serum and urinary biochemical markers of bone turnover and in bone mineral density. Bone density increased by 6% following 1 year of treatment of thyrotoxicosis. Bone turnover was balanced within 2 weeks of starting treatment for thyrotoxicosis. Urinary deoxypyridinoline was the most accurate indicator of thyrotoxic bone resorption. Serum bone-alkaline phosphatase continued to be raised after 1 year of treatment indicating continuing bone formation. Osteocalcin, serum deoxypyridinoline and serum pyridinoline were less sensitive in documenting bone remodelling during treatment of thyrotoxicosis.

A further longitudinal study was performed to study serum levels of osteotropic cytokines in patients with hyperthyroidism of differing aetiologies. We demonstrated that serum IL6 and IL8 were elevated in untreated thyrotoxicosis, that there was no significant difference between levels in the autoimmune Graves disease or the non autoimmune toxic nodular goitre and that they fell as thyroid levels normalised with medical treatment.

The effects of triiodothyronine (T3) on osteotropic cytokine production on cells of human osteoblast lineage were investigated in vitro. We found that T3 increased IL6 and IL8 production and mRNA expression from both human bone marrow stromal cells (hBMS) and the human osteosarcoma cell line MG63 cell but not from the more differentiated human osteoblasts (hOb) or the SaOs-2 cell line.

Finally, the expression of thyroid hormone receptor (TR) isoforms in these osteoblasts was studied. The three main TR isoforms alpha 1, beta 1 and beta 2 were expressed in all osteoblasts. However, expression and endogenous TR activity predominated in hBMS cells rather than in hOb.

This work has demonstrated the profound effect of thyroid hormones on bone turnover and highlighted the role of human bone marrow stromal cells as important targets for T3 action.