A Slightly Suppressive Dose of L-Thyroxine Does Not Affect Bone Turnover and Bone Mineral Density in Pre- and Postmenopausal Women With Nontoxic Goitre

Abstract

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.

Subclinical hyperthyroidism: clinical features and treatment options

“…In several cross-sectional studies, bone mineral density was decreased at multiple sites in pre-(66 -69) and postmenopausal women (69 -74) with exogenous (66 -69, 72) or endogenous (68, 73 -74) subclinical hyperthyroidism. This finding, however, was not confirmed in other cross-sectional observations in pre- (70, 75 -86) and postmenopausal conditions (76, 79 -82, 84, 87 -91), and in exogenous (76, 77 -83, 85 -90) and endogenous conditions (75,84). Similar results were found in longitudinal studies with decreased or normal bone mineral density in pre-(92 -94) or postmenopausal women (72, 91, 92 -95) with exogenous subclinical hyperthyroidism.…”

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

“…A significant increase in BGP and AP in patients on L-T4 is reported in several cross-sectional trials (Taelman et al, 1990;Stepan & Limanova, 1992) but not in others (Ross et al, 1990;De Rosa et al, 1995). The bone turnover markers in our euthyroid goitrous patients showed an early and progressive significant increase during the 12 months' L-T4 therapy, with a similar pattern in pre-and post-menopausal women; however, no relationship was found between bone turnover markers and thyroid function tests.…”

“…Our finding of a positive correlation between bone formation marker serum BGP and bone resorption marker OHP at the 3-month assessment, irrespective of menopausal status, is consistent with the activation of new remodelling cycles with stimulation of osteoclastic and osteoblastic activity at the beginning of L-T4 administration. The failure to provide evidence of increased fracture rate in retrospective studies (Solomon et al, 1993) and the negative results of several recent cross-sectional studies into the potential detrimental effects of L-T4 therapy on the skeleton (Franklyn et al, 1992;Marcocci et al, 1994;De Rosa et al, 1995) support the hypothesis of a transient and reversible bone mass reduction due to new bone formation at the end of the resorptive phase. On the other hand, in hyperthyroid patients BMD was not fully restored 2 years after recovery (Krolner et al, 1993).…”

Effects on Bone Mineral Density by Treatment of Benign Nodular Goiter with Mildly Suppressive Doses of <i>L</i>-Thyroxine in a Cohort Women Study

“…The impact of subclinical hyperthyroidism on bone metabolism is still a matter of debate [10,13,14,15]. …”