A Modest Protective Effect of Thyrotropin against Bone Loss Is Associated with Plasma Triiodothyronine Levels

BackgroundThe independent skeletal effect of thyrotropin (thyroid stimulating hormone, TSH) has been suggested in animal studies. However, clinical data on the association between bone loss and variations in TSH levels is inconsistent. This study aimed to investigate the relationship between TSH levels and bone mineral density (BMD).MethodsWe conducted a cross-sectional study with 37,431 subjects (33,052 cases with euthyroidism and 4,379 cases with subclinical thyroid dysfunction) aged over 35 years. We performed thyroid function tests and measured BMD at the lumbar spine, femur neck, and total hip.ResultsLevels of TSH and T3 were positively correlated in women (r = 0.076, P = 0.001) and uncorrelated in men. In both men and women, TSH levels correlated positively and T3 levels correlated negatively with BMD at all skeletal sites in age and body mass index adjusted analyses. BMD increased steadily with TSH levels from the subclinical hyperthyroid to subclinical hypothyroid range in subjects with T3 levels in the highest tertile (119.5–200.0 ng/dL), but was no longer significant in subjects with lower plasma T3 levels.ConclusionsThe variations in TSH levels within the euthyroid and subclinical range were positively correlated with BMD in healthy men and women. The negative effect of T3 on BMD appears to be compensated for by increased TSH in subjects with plasma T3 levels in the upper normal range.研究背景 促甲状腺素（thyroid stimulating hormone, TSH）的独立骨骼效应已在动物实验中被提出。然而，关于骨丢失与促甲状腺素水平波动之间关联的临床数据并不一致。本研究旨在探讨促甲状腺素水平与骨密度（bone mineral density, BMD）之间的关联。 研究方法 本研究纳入37431名35岁以上受试者，其中33052名甲状腺功能正常者、4379名亚临床甲状腺功能异常者，开展横断面研究。所有受试者均接受甲状腺功能检测，并测定腰椎、股骨颈及全髋部位的骨密度。 研究结果 女性受试者的促甲状腺素与三碘甲状腺原氨酸（T3）水平呈正相关（r=0.076，P=0.001），男性则无明显相关性。在校正年龄与体质量指数的分析中，无论男性还是女性，促甲状腺素水平与各骨骼部位的骨密度均呈正相关，而三碘甲状腺原氨酸水平则呈负相关。在三碘甲状腺原氨酸水平处于最高三分位组（119.5~200.0 ng/dL）的受试者中，骨密度随促甲状腺素水平从亚临床甲状腺功能亢进区间升至亚临床甲状腺功能减退区间呈持续升高趋势；但在血浆三碘甲状腺原氨酸水平较低的受试者中，该趋势不再具有统计学显著性。 研究结论 在健康男性与女性中，甲状腺功能正常及亚临床区间内的促甲状腺素水平波动与骨密度呈正相关。在血浆三碘甲状腺原氨酸水平处于正常上限区间的受试者中，三碘甲状腺原氨酸对骨密度的负向效应似乎可通过升高的促甲状腺素水平得到代偿。