Thyroid hormones play critical roles in regulating bone turnover and maintaining bone mass. However, the relationship among thyroid hormones, their sensitivity indices, bone mineral density (BMD) and fracture risk remained unclear in the Chinese osteoporotic population. This study aimed to investigate the associations between thyroid hormones, their sensitivity indices, and both volumetric BMD (measured by quantitative computed tomography, QCT-BMD), areal BMD (measured by dual-energy X-ray absorptiometry, DXA BMD), as well as the risk of vertebral fractures, among primary osteoporotic individuals aged over 50 years old of euthyroid adults in northern China (north of the Yellow River). A total of 1, 386 men and postmenopausal women (aged ≥50 years) with euthyroidism and primary osteoporosis were recruited from Beijing Jishuitan Hospital during January 2021 to December 2024. Participants were divided into two groups: those without vertebral fractures (n = 856) and those with vertebral fractures (n = 530). Demographic characteristics, serum bone turnover markers (ALP, tP1NP, β-CTX, OC, PTH), thyroid hormones (TT4, TT3, TSH, FT3, FT4), thyroid hormone sensitivity indices (FT4/FT3, TSHI, TT4RI, TFQI), lumbar QCT-BMD, lumbar DXA-BMD, and total hip DXA-BMD were compared between groups. Univariate and multivariate logistic regression analyses, restricted cubic spline (RCS) regression, and subgroup analyses were performed to evaluate the independent effects of thyroid hormones and their sensitivity indices on BMD measures and vertebral fracture risk, adjusting for potential confounders including age, sex, BMI, smoking, alcohol consumption, diabetes, hypertension, and hyperlipidemia. The vertebral fracture group exhibited significantly higher TT3 levels compared to the non-fracture group (TT3: 1.98 [1.60, 2.89] vs. 1.76 [1.50, 1.91] nmol/L, P < 0.001), while TT4 levels were significantly lower than the non-fracture group (TT4: 89.50 [39.65, 101.00] vs. 103.00 [85.60, 115.00] nmol/L, P < 0.001). No significant difference was observed for TSHI, TT4RI, or TFQI between groups. After multivariable adjustment, elevated TT3 remained independently associated with increased lumbar fracture risk (OR (95% CI): 1.02 [1.01-1.04], P = 0.018), the positive relationship remained significant in RCS analysis (P < 0.001). TSH showed a significant positive association with lumbar QCT-BMD (β (95% CI): 0.89 [0.07-1.71], P = 0.034) and in RCS analysis(P = 0.013). In contrast, FT4/FT3 and FT3 were positively associated with lumbar QCT-BMD in the adjusted logistic regression (β (95% CI): 12.08 [6.18~17.98], P < 0.001; β (95%CI):3.69 (0.31 ~ 7.07), P = 0.033), but exhibited a nonlinear and negative association with lumbar QCT-BMD in RCS analysis (P = 0.003, P = 0.008). Subgroup analyses stratified by gender, age, BMI, diabetes, hypertension, hyperlipidemia, cardiovascular disease, smoking, and alcohol drinking revealed significant interaction effects between FT4/FT3 and lumbar QCT-BMD in gender-specific (P-interaction = 0.046) and age-specific analysis (P-interaction = 0.021). Notably, in individuals under 60 years old, higher FT4/FT3 was associated with increased lumbar QCT-BMD(β (95% CI): 10.62 [2.84-18.40], P = 0.009). Our findings demonstrated that thyroid hormones-specifically FT3, TT3, TSH-and the peripheral thyroid hormone sensitivity index FT4/FT3 were more strongly associated with vertebral fracture risk and bone mineral density. Notably, these associations were more pronounced with vBMD measured by QCT. Collectively, these results highlighted the potential role of FT3, TT3, TSH, and the peripheral thyroid sensitivity index FT4/FT3 as indicators of bone mass and fracture risk prediction in this population.
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