Prospective study of bone loss in pre- and post-menopausal women on L-thyroxine therapy for non-toxic goitre

OBJECTIVE Hyperthyroidism is associated with increased bone turnover and bone resorption, but the effects of suppressive doses of thyroxine in treating non-toxic goitre remain unclear. We carried out a longitudinal study to evaluate the effect on bone of L-thyroxine (L-T4) therapy in women with non-toxic goitre. SUBJECTS Forty Caucasian women, 19 of whom were pre-menopausal and 21 post-menopausal, were studied before and after 12 months' L-T4 therapy for non-toxic goitre; 40 women matched for age, body mass index and menopausal status were used as controls. DESIGN The minimal dosage of L-T4 (mean +/- standard error = 1.5 +/- 0.1 mu g/kg(-1) day(-1)) was given to each patient to obtain subnormal but detectable serum TSH (less than or equal to 0.2 mU/l). Patients and controls were assessed for minor determinants of bone loss rate, such as genetic and behavioural factors. MEASUREMENTS Bone mineral density (BMD) of the lumbar spine, femoral neck, trochanter and Ward's triangle was measured by dual-energy X-ray absorptiometry at baseline and 12 months; serum and urine markers of bone turnover was measured at baseline, 3, 6 and 12 months. RESULTS No significant difference was detected in BMD values between patients and controls either at presentation or at the 12-month follow-up. Pre-menopausal patients showed a significant decrease in femoral neck BMD (-1.7 +/- 0.6%, P < 0.05) while controls showed no change + 0.2 +/- 0.9%, P = NS). Postmenopausal patients showed a significant decrease in BMD of the lumbar spine (-1.3 +/- 0.6%, P < 0.05; controls + 0.0 +/- 0.4%, P = NS), femoral neck (-1.5 +/- 0.6%, P < 0.05; controls -1.2 +/- 0.8%, P = NS) and trochanter (-2.1 +/- 0.8%, P < 0.05; controls -1.4 +/- 0.9%, P = NS). In both pre-and post-menopausal patients the serum markers of bone turnover, alkaline phosphatase and osteocalcin, showed an early and progressive increase. A linear relationship was found only between the 3-month values of serum osteocalcin and the urine hydroxyproline/creatinine ratio in both pre-menopausal (r = 0.87, P < 0.01) and post-menopausal (r = 0.72, P < 0.05) patients. No correlation was found between bone loss or changes in bone turnover markers and L-T4 dose or thyroid hormone levels. CONCLUSION This longitudinal study suggests that TSH-suppressive therapy with L-thyroxine for nontoxic goitre significantly increases the bone mineral turnover and might contribute to a BMD reduction, more marked on cortical bone, in both pre-and postmenopausal women.