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 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.

A slightly suppressive dose of L-thyroxine does not affect bone turnover and bone mineral density in pre- and postmenopausal women with nontoxic goitre.

There are controversial reports on the potential role of L-thyroxine administration as a risk factor for osteoporosis. We studied bone mass and metabolism in a homogeneous series of 50 Caucasian women, 25 premenopausal and 25 postmenopausal, having nontoxic goitre treated with slightly suppressive L-thyroxine doses (50-200 micrograms/day) with subnormal serum TSH and normal thyroid hormone levels. These patients were matched with 50 controls for age, sex, body mass index, menopausal and thyroid disease. Patients and controls were also investigated for minor determinants of bone loss, such as hereditary and life-style factors. Patients and controls filled in a questionnaire and underwent physical examination, routine laboratory tests and calciotropic and thyroid hormone assay. Bone mineral turnover was evaluated by determining serum osteocalcin, alkaline phosphatase, tartrate-resistant acid phosphatase, calcium, phosphate, urine hydroxyproline/creatinine and calcium/ creatinine ratio. Bone mineral density was measured by dual-energy X-ray absorptiometry at the lumbar spine, femoral neck, trochanter and Ward's triangle. No difference in bone mineral density or biochemical markers was found between patients and controls; bone density and turnover were significantly affected by menopausal status. No relationship between bone density or turnover values and L-thyroxine administration was found. A significant positive correlation was found between osteocalcin and the hydroxyproline/creatinine ratio in premenopausal and postmenopausal patients, but not in controls. Our study suggests that slightly suppressive L-thyroxine administration in nontoxic goitre can activate bone turnover but constitutes neither an actual risk factor for bone loss nor, consequently, for osteoporotic fractures.