High titers of thyroid peroxidase antibodies as a potential risk factor for osteoporosis: A cross-sectional NHANES study and bidirectional Mendelian randomization analysis

This study investigates the associations between thyroid autoimmunity in Hashimoto's thyroiditis (HT), particularly thyroid peroxidase antibody (TPOAB) and thyroglobulin antibody (TGAB) titers, and bone mineral density (BMD) and fracture risk, and explores potential causal relationships using Mendelian randomization (MR) analysis. Data were obtained from nationally representative adults in the NHANES 2007-2010 cohort. Associations between thyroid autoantibody levels, BMD at the femoral neck and lumbar spine, and fracture risk were analyzed using multivariable linear and logistic regression with adjustments for demographic, lifestyle, and biochemical factors. A 2-sample bidirectional MR analysis was performed to assess the causal link between HT and osteoporosis (OP). After accounting for confounders, positive status and higher titers of TPOAB were significantly linked to decreased BMD at the femoral neck and lumbar spine (P < .05). TGAB positivity was independently associated with lower lumbar spine BMD, while the association for femoral neck BMD disappeared after multivariable adjustment. TPOAB seropositivity was associated with elevated spinal fracture risk in a dose-dependent manner, and receiver operating characteristic (ROC) analysis showed a moderate discriminatory ability of TPOAB titers for spinal fracture. MR analyses indicated a potential causal association between HT and OP, and sensitivity analyses showed generally consistent directions of effect and did not indicate substantial heterogeneity or horizontal pleiotropy. Increased thyroid autoantibodies, notably higher TPOAB titers, correlate with bone loss and elevated spinal fracture risk, and relevant genetic data suggest a causal association. Thyroid autoimmunity, particularly raised TPOAB levels, may aid the identification of people with low BMD. Additional prospective research is required to determine whether antibody titers enhance fracture risk stratification and act as modifiable therapeutic targets.