Thyroid hormone status within the physiological range affects bone mass and density in healthy men at the age of peak bone mass

Abstract

Context: The hormonal factors involved in the regulation of peak bone mass (PBM) in men have not been fully investigated. Apart from gonadal steroids and somatotropic hormones, thyroid hormones are known to affect bone maturation and homeostasis and are additional candidate determinants of adult bone mass. Objective: We aimed to investigate between-subject physiological variation in free and total thyroid hormone concentrations, TSH, and thyroid binding globulin (TBG) in relation to parameters of bone mass, geometry, and mineral density in healthy men at the age of PBM. Design and setting: We recruited 677 healthy male siblings aged 25-45 years in a cross-sectional, population-based study. Areal and volumetric bone parameters were determined using dual-energy x-ray absorptiometry (DXA) and peripheral quantitative computed tomography (pQCT). Total and free thyroid hormones, TBG, and TSH were determined using immunoassays. Results: Free and total thyroid hormone concentrations were inversely associated with bone mineral density (BMD) and bone mineral content (BMC) at the hip and total body (free triiodothyronine (FT 3 ), total T 3 (TT 3 ), and total T 4 (TT 4 )) and at the spine (FT 3 ). TBG was negatively associated with BMC and areal BMD at all sites. At the radius, cortical bone area was inversely associated with TT 3 , TT 4 , and TBG, and trabecular bone density was inversely associated with free thyroxine, TT 4 , and TBG. We observed inverse associations between cortical bone area at the mid-tibia and FT 3 , TT 3 , TT 4 , and TBG. No associations between TSH and DXA or pQCT measurements were found. Conclusion: In healthy men at the age of PBM, between-subject variation in thyroid hormone concentrations affects bone density, with higher levels of FT 3 , TT 3 , TT 4 , and TBG being associated with less favorable bone density and content.

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

“…Similar to the current study, Murphy et al also reported an inverse correlation between fT 4 and BMD by multiple linear regression. Other studies have also demonstrated that women with higher fT 4 levels within the normal reference range have lower BMD, but they found little or no association between BMD and TSH (10,11,12,25). Interestingly, in a study from Taiwan using a similar cross-sectional design in women of comparable age to the current study, no relation was demonstrated between TSH and BMD, while the authors found a significant but weak correlation between BMD and fT 4 in postmenopausal women (11).…”

“…Only a few studies have investigated a possible effect of the fT 4 concentration in subclinical thyroid dysfunction (10,11,12), which by definition lies within the reference range. Moreover, it is possible that the subjects with subclinical hyperthyroidism and a fT 4 level in the upper normal range have more adverse clinical outcomes than the subjects with subclinical hyperthyroidism and fT 4 levels in the middle or lower reference range, or compared with euthyroid individuals (3).…”

Thyroid-stimulating hormone within low-normal range is related to imbalance of bone remodeling in euthyroid postmenopausal women with osteoporotic fractures

“…The results of in vitro experiments support the observations that TSH negatively regulates osteoclastogenesis and exerts a protective effect on bone [3]. According to recent reports, variations of serum TSH within the physiological range do not greatly influence BMD and there is no correlation between bone turnover markers and TSH [4,5]. On the other hand, subclinical hyperthyroidism, and even thyroid function within the upper normal range, have been shown to affect bone density and the risk of nonvertebral fractures in postmenopausal women [6,7].…”

Heredity and lifestyle in the determination of between-subject variation in thyroid hormone levels in euthyroid men

“…This suggests an individual set point for pituitary-thyroid axis function (1). We and others have shown that this between-subject variation in TH levels, although within the normal range, is nevertheless associated with a number of clinical parameters such as bone mass, BMI, metabolic indices, and heart rate (2,3,4,5). The physiological basis of the set point of this axis is poorly understood (6).…”