BONE-MINERAL DENSITY IN POSTMENOPAUSAL WOMEN TREATED WITH L-THYROXINE

PURPOSE: To determine if bone mineral density is decreased in postmenopausal women treated with l-thyroxine, and, if any decrease is observed, whether it is related to overtreatment with thyroid hormone, to deficiency of calcitonin, or to other factors. PATIENTS AND METHODS: The study consisted of 19 postmenopausal women between 50 and 75 years of age treated with l-thyroxine for 5 years or longer, and 19 matching control subjects with no thyroid disease. Bone mineral density of the spine and hip was measured by dual-photon absorptiometry. Plasma calcitonin concentrations and serum thyroid hormone levels were determined by radioimmunoassays. RESULTS: The l-thyroxine-treated women had lower bone density in the lumbar spine (1.013 g/cm2 [95% confidence interval, 0.945 to 1.081] versus 1.134 g/cm2 [1.026 to 1.242], p = 0.043); in the femoral neck (0.736 g/cm2 [0.694 to 0.778] versus 0.809 g/cm2 [0.747 to 0.872], p = 0.040); in Ward's triangle (0.576 g/cm2 [0.530 to 0.623] versus 0.694 g/cm2 [0.617 to 0.770], p = 0.011); and in the trochanteric area (0.626 g/cm2 [0.581 to 0.672] versus 0.722 g/cm2 [0.651 to 0.794], p = 0.027). The maximal increase in calcitonin following calcium infusion was 1.37 ng/L (95% confidence interval, -0.44 to 3.17) in the l-thyroxine-treated patients versus 18.8 ng/L (95% confidence interval, 10.0 to 27.5) in normal women, p < 0.001. The average dose of l-thyroxine was 120-mu-g/day; 16 of the 19 patients had normal serum thyroxine levels. However, TSH levels were low in 13 of the 19, suggesting that l-thyroxine treatment was supraphysiologic. Seven of the 19 patients had a history of hyperthyroidism in the distant past; these patients, considered separately, had significantly reduced bone density in the hip. The other 12 patients, considered separately, did not have a statistically significant loss of bone density. CONCLUSIONS: Long-term l-thyroxine therapy is associated with decreased density of the spine and hip. Since subclinical hyperthyroidism, decreased calcitonin responsiveness, and a history of hyperthyroidism were demonstrated in some or all of these patients, these factors must be considered as possible causes of the decreased bone density.