Mechanism of Thyroid Hormone-Induced Osteoporosis

Thyroid hormone T3 is essential for normal skeletal growth and development. Excess T3, especially in adult individuals, can lead to bone loss and increased susceptibility to fractures. Data from our laboratory showed that in vitro systems, T3 increases the local production of both a critical bone growth factor, insulin-like growth factor-I. It also potentiated interleukin-1 IL-1 stimulated production of a cytokine with significant importance for osteoclastogenesis, interleukin-6 IL-6. The current studies were undertaken to determine whether these local factors are important in the effects of T3 to stimulate osteoblast proliferation and to generate bone-phenotypic proteins, i.e., alkaline phosphatase, osteocalcin, collagen and in the effects of T3 to stimulate bone resorption. The data obtained supports these conclusions, as antibody, antisense or antagonist peptide to the IGF-I receptor inhibited the anabolic effects of T3 and antibody to the IL-6 receptor inhibited the bone resorbing effect of T3. Also, studies were undertaken to investigate the mechanisms by which T3 stimulates the production of insulin-like growth factor-I and interleukin-6. IL-i increased IL-6 mRNA and IL-6 promoter construct expression, and in some studies T3 had small stimulatory effects and enhanced the response to IL-i. The studies on the mechanism of the thyroid effect on IGF-I synthesis have not yet provided any conclusive results and are still ongoing.