Low bone mineral density is related to high physiological levels of free thyroxine in peri-menopausal women

Abstract

Objective: To determine whether thyroid hormone (free thyroxine (fT 4 )) rather than TSH is directly related to bone mineral density (BMD). Design: Cross-sectional population cohort study of peri-menopausal women. Methods: Of a sample of 6846 peri-menopausal Dutch women who participated in an osteoporosis-screening programme, a cohort of 2584 was randomly selected for the assessment of thyroid function (TSH, fT 4 and thyroid peroxidase antibodies (TPO-Abs)). TPO-Ab-positive women, with a previous history of thyroid dysfunction, overt thyroid disease, subclinical hypothyroidism, osteoporosis or bilateral oophorectomy and those receiving thyroid hormone or hormone replacement therapy were excluded. Of 1477 eligible women, 1426 had TSH and fT 4 within the reference range and 51 had low or undetectable serum TSH. BMD was measured at the lumbar spine and low BMD was defined as !0.937 g/cm 2 .Results: The mean BMD in the 51 women with low or undetectable serum TSH was 0.984 g/cm 2 compared with 1.001 g/cm 2 in the remaining 1426 (tZ0.94, PZ0.35); 33% of women with low or undetectable serum TSH had low BMD compared with 34% in 1426 euthyroid women. High fT 4 but not low TSH in euthyroid women was related to low BMD by multiple logistic regression corrected for age, BMI and smoking (OR, 1.30; 95% CI, 1.02-1.69). Conclusions: Higher fT 4 levels within the normal reference range but not low or undetectable serum TSH were independently related to decreased BMD at lumbar spine in peri-menopausal women.

TSH-receptor antibodies may prevent bone loss in pre- and postmenopausal women with Graves' disease and Graves' orbitopathy

“…Our study demonstrates lower bone mineral density at axial skeleton (spine and hip) in hyperthyroid perimenopausal women with Graves' disease compared to healthy controls in accordance with results of many other authors (12,13). Some studies have proved that in premenopausal women this decrease in the bone density is observed mainly in cortical bone (femoral neck) similarly to other examples of secondary osteoporosis (14).…”

“…In the studies of van Rijn and cols. similar association was found in euthyroid perimenopausal women -higher fT4 levels within the normal reference range were independently related to decreased BMD at lumbar spine (13).…”

“…Physiologically TSH stimulates T4 secretion by thyroid follicular cells (13,19), however, the effects of the hypothalamic-pituitary-thyroid (HPT) axis on its target organs are related to levels of TH and to the activities of the deiodinase enzymes that regulate the local concentration of triiodothyronine (T3). Thus, T4 is a pro-hormone of the biologically active T3 (19,20).…”

The impact of thyroid autoimmunity (TPOAb) on bone density and fracture risk in postmenopausal women

“…TSH even moderately below or above the reference range is an independent predictive factor for vertebral fractures. 13,15,[19][20][21][22] The HUNT2 study revealed a weak association between mild increase or decrease of TSH and a higher risk of hip fractures, fracture risk being evaluated on the basis of the information given by examiners during the 12.5 years of follow-up. 23 The same study described an association between TSH in the hyperthyroid range and low bone mineral density in the forearm.…”

The Excess Risk of Major Osteoporotic Fractures in Hypothyroidism Is Driven by Cumulative Hyperthyroid as Opposed to Hypothyroid Time: An Observational Register-Based Time-Resolved Cohort Analysis

“…This is in agreement with previous studies demonstrating the increased susceptibility of postmenopausal women to the accelerated bone loss in hyperthyroid states brought about by estrogen deficiency. (7,36,37) Hypothetically, because estradiol levels are already low, indeed lower than in men of similar age, a lowering of already strongly raised gonadotropin levels due to undertreated hypothyroidism would not exacerbate bone loss.…”