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

Abstract

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 micrograms/kg-1 day-1) was given to each patient to obtain subnormal but detectable serum TSH (< or = 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). Post-menopausal 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.

Conclusions: This longitudinal study suggests that TSH-suppressive therapy with L-thyroxine for non-toxic goitre significantly increases the bone mineral turnover and might contribute to a BMD reduction, more marked on cortical bone, in both pre- and post-menopausal women.