ETIDRONATE INHIBITS THE THYROID HORMONE-INDUCED BONE LOSS IN RATS ASSESSED BY BONE-MINERAL DENSITY AND MESSENGER-RIBONUCLEIC-ACID MARKERS OF OSTEOBLAST AND OSTEOCLAST FUNCTION

TSH-suppressive doses of thyroid hormone are associated with bone loss . We have previously reported that L-T4 decreases femoral, but not ver tebral bone mineral density (BMD) in rats. As bisphosphonates are able to decrease bone resorption, especially in high bone turnover states, we investigated the potential effects of etidronate disodium (EHDP) o n L-T4-induced bone loss in the rat model by assessing BMD and gene ex pression of osteoblast (osteocalcin, osteopontin, type I collagen, and alkaline phosphatase), osteoclast (tartrate-resistant acid phosphatas e), and cell growth (histone) markers in the skeleton. L-T, administer ed for 20 days decreased BMD in the femur, but had no effect on the lu mbar spine. EHDP alone had no effect on femoral or vertebral BMD, but did prevent the L-T4-induced bone loss in the femur. L-T, increased mR NA levels of alkaline phosphatase, tartrate-resistant acid phosphatase , and histone H4 in the femur, but not in the vertebrae. EHDP, which a lone had no effect on gene expression in the femur or vertebrae, inhib ited the effect Of L-T, on mRNA markers in the femur. The results demo nstrate that EHDP can prevent the L-T4-induced decrease in femoral BMD in rats that is associated with the prevention of changes in mRNA mar kers of osteoclast and osteoblast function. EHDP and other bisphosphon ate compounds may be useful in the prevention of thyroid hormone-induc ed bone loss in humans.