A Mendelian randomization study investigating the causal relationship between 35 blood and urine metabolite biomarkers and postmenopausal osteoporosisShort Communication

Objective: This study intends to investigate the causal association between 35 blood and urine biomarkers and postmenopausal osteoporosis (PMOP) through two-way Mendelian randomization analysis. Methods: This study adopted a two-way Mendelian randomization analysis, with data sourced from the UK Biobank and the Finnish Biobank Study. Among them, the R12 dataset of the Finnish Biobank Study was used as the test set, and the R11 dataset as the validation set. The study regarded 35 biomarkers as exposure factors and PMOP (a condition characterized by decreased bone density after menopause) as the outcome variable. It was analyzed through methods such as the inverse variance weighting method, the weighted median method, and MR-Egger regression, and combined with the MR-PRESSO test to exclude the influence of pleiotropy. Results: In the positive direction analysis, alkaline phosphatase, glomerular filtration rate, sex hormone-binding globulin, and total protein showed statistical significance in both the test set and the validation set, and they were all risk factors for PMOP. Direct bilirubin and uric acid demonstrated statistical significance in both the test and validation sets, and they served as protective factors against PMOP. In the negative direction analysis, alkaline phosphatase showed statistical significance in both the test set and the validation set, being a positive result for PMOP; sex hormone-binding globulin and total bilirubin showed statistical significance in both the test set and the validation set, being negative results for PMOP. Conclusion: Employing bidirectional Mendelian randomization methodology, this investigation elucidated the causal relationships between multiple hematological and urinary biomarkers and PMOP. The results provide promising biomarker candidates for future diagnostic and therapeutic strategies targeting PMOP, while simultaneously establishing a robust framework for subsequent exploration of its underlying pathophysiological mechanisms.