The impact of denosumab and calcitriol on asthma risk and lung function: a drug target mendelian randomization study

Osteoporosis and asthma are prevalent chronic conditions that significantly impact public health. Inflammatory cell merging, leading to reduced bone density, increases the risk of fractures, while asthma is a chronic respiratory disease characterized by airway inflammation and bronchoconstriction. More and more emerging research suggests a potential connection through shared pathways and biological mechanisms. In this study, we aim to investigate the causal effect of anti-osteoporosis drug treatment on chronic disease asthma through the Mendelian randomization (MR) analysis method.

In our study, we employed a two-stage study design, utilizing observational data from the National Health and Nutrition Examination Survey (NHANES) and summary statistics data from genome-wide association studies (GWAS) with a large sample of European adults. Section-cross research was performed using NHANES datasets and analysis of the risk of asthma with bone mineral density (BMD) through a risk proportion regression model. After that, a two-sample MR analysis was performed to investigate the causal effect of anti-osteoporosis drug therapy on asthma. Finally, sensitivity analysis was conducted to evaluate the stability of the results.

Our study revealed a non-linear association between femur BMD and asthma risk, with a critical inflection point at a BMD value of 1.114 g/cm². MR analysis indicated that denosumab did not exert a causal effect on asthma risk (OR = 1.008, 95% CI: 0.994-1.022, P = 0.285) but was associated with improved lung function (β = 0.085, 95% CI: 0.006-0.164, P = 0.035). Conversely, calcitriol exhibited a protective effect against both asthma (OR = 0.931, 95% CI: 0.894-0.969, P < 0.001) and lung function decline (β = 0.294, 95% CI: 0.062-0.525, P = 0.013). These findings suggest a pleiotropic role for these anti-osteoporosis drugs in respiratory health.

This study provides novel insights into the complex relationships between osteoporosis treatments, bone health, and asthma risk. The use of MR analysis enhances the reliability of our findings and highlights the potential benefits of osteoporosis treatments in reducing asthma risk and improving lung function. These results call for further research and may have implications for developing integrated treatment approaches for individuals managing osteoporosis and asthma.