Osteoporosis and depression in perimenopausal women: From clinical association to genetic causality

Osteoporosis and major depressive disorder (MDD) represent two significant health challenges globally, particularly among perimenopausal women. This study utilizes NHANES data and Mendelian randomization (MR) analysis to explore the link between them, aiming to provide a basis for intervention strategies for this group. The study analyzed NHANES 2007–2018 data using weighted logistic regression in R software to evaluate the link between MDD and osteoporosis risk. Then, a two-sample MR analysis with GWAS summary statistics was performed, mainly using the IVW method. Additional validation included MR Egger, Weighted Median, Mode, and MR-PRESSO methods. The research analysis indicated a significant link between MDD and the risk of osteopenia/osteoporosis. Our analysis revealed a significant positive relationship between MDD and both femoral neck osteoporosis (OR = 6.942 [95 % CI, 1.692–28.485]) and trochanteric osteoporosis (OR = 4.140 [95 % CI, 1.699–10.089]). In analyses related to osteopenia, a significant positive correlation was observed between MDD and both total femoral osteopenia (OR = 3.309 [95 % CI, 1.577–6.942]) and trochanteric osteopenia (OR = 2.467 [95 % CI, 1.004–6.062]). Furthermore, in the MR analysis, genetically predicted MDD was causally associated with an increased risk of osteoporosis via the IVW method (P = 0.013). Our study was limited by potential selection bias due to excluding subjects with missing data, and its applicability was primarily to European and American populations. Integrating NHANES and MR analyses, a robust correlation between MDD and osteoporosis was identified, emphasizing the significance of addressing this comorbidity within clinical practice and meriting further investigation.