The Effects of Triiodothyronine on Bone Metabolism in Healthy Ambulatory Men

Abstract

The purpose of the present study was to determine the effects of supraphysiologic doses of triiodothyronine (T(3)) on skeletal metabolism, calcium balance, and the calciotropic hormones. Seven healthy, lean men were studied in an inpatient metabolic unit over a 63-day period. All volunteers received oral T(3) at doses of 50-75 microg/d. There was a prompt and sustained increase in calciuria and an overall net negative calcium balance. The pattern of changes in serum osteocalcin, urinary deoxypyridinoline (DPD)/creatinine ratio, and serum bone-specific alkaline phosphatase indicated an early increase in bone resorption followed by a late, incomplete compensatory increase in bone formation. Cumulative net calcium loss was 18.5 +/- 5.4 g over the 63-day treatment period, averaging 218.5 +/- 41.4 mg/d. This represents 0.22% +/- 0.075% of the total skeletal calcium content. The cumulative net calcium loss over the 63-day treatment period was highly correlated with the change in DPD (r = -0.95, p = 0.001). Prompt increases in corrected serum calcium values resulted in serum intact parathyroid hormone (iPTH) levels decreasing by 30.4% (p = 0.08). Bone mineral density showed no change. We conclude that T(3) accelerates bone turnover and that bone formation does not increase acutely to prevent bone loss.

Triiodothyronine increases calcium loss in a bed rest antigravity model for space flight

“…The increase in those subjects treated with T 3 was significantly greater than that in the bed rest group. The increased rate of bone resorption is in harmony with that seen in patients with hyperthyroidism and in a longer study of healthy subjects [21] and in subjects at bed rest or in space flight [10,11,13,15]. These data are also consistent with earlier reports of decreased gut calcium absorption [32][33][34][35][36] and increased calcium excretion in hyperthyroid patients at steady state [5,6].…”

“…As noted previously, hyperthyroidism shares features with immobilization in its effect on the skeletal system [5,6,17]. We hypothesized that treatment with low doses of thyroid hormone during bed rest would increase bone resorption with greater loss of calcium earlier than immobilization alone [18][19][20][21]. This strategy would require monitoring and readjustment of thyroid hormone doses after the normal physiologic response to lower thyroid-stimulating hormone (TSH).…”

Reductions in serum levels of LDL cholesterol, apolipoprotein B, triglycerides and lipoprotein(a) in hypercholesterolaemic patients treated with the liver‐selective thyroid hormone receptor agonist eprotirome

“…Echocardiography showed no changes in cardiac function or morphology typical of thyroid hormone excess. Stable bone formation and resorption markers indicated no negative effects on bone metabolism, in contrast to experience with other thyroid hormone analogues in humans [14][15][16]. The isolated increase in serum P1NP has also been observed in patients treated with statins [34] and is unlikely to reflect a skeletal effect.…”

Lipid lowering with thyroid hormone and thyromimetics

“…Drastically speaking, a successful thyromimetic for lipid lowering should induce 'thyrotoxicosis' in the liver but be inert in all other organs including the pituitary. Influence on heart rate and heart rhythm, loss of bone mass, and myopathy are such side-effects that have been seen when normal subjects have been exposed to excess T3 [45], and also when some less specific thyroid hormone analogs have been tested in patients with cardiac failure [46 ,47]. Thus, the first human studies of selective thyromimetics were designed to very carefully monitor possible thyroidrelated side-effects both by following circulating thyroid hormones and TSH and by careful clinical scoring of symptoms of hyperthyroidism and hypothyroidism.…”