Related Experiment Video
Updated: Sep 17, 2025
Refined Murine Model of Idiopathic Pulmonary Fibrosis
Published on: June 17, 2025
Calcium Supplementation, Genetic Susceptibility, and Idiopathic Pulmonary Fibrosis Risk: A Prospective Study
Bingxin Shang1, Yuxin Yao1, Yujia Xie1
1Department of Occupational & Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China; Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Background:
The association between calcium supplementation and the risk of incident idiopathic pulmonary fibrosis (IPF) is largely unknown.
Objectives:
This study aimed to investigate the association of calcium supplementation with IPF incidence and further explore the modifying effect of genetic susceptibility.
Methods:
This study analyzed 472,468 participants from the UK Biobank. The information on the calcium supplement use was obtained from the baseline touchscreen questionnaire, and the IPF case was identified using the International Classification of Diseases with the 10th edition code J84.1, and further excluded secondary pulmonary fibrosis-related diseases. We used the Cox proportional hazard model to assess the association between calcium supplementation and the risk of IPF incidence. Besides, we calculated the IPF-specific polygenic risk score for each individual and assessed the modifying effect of genetic susceptibility.
Results:
During a median follow-up of 12.82 y, a total of 1859 new-onset IPF cases were identified. After adjusting for traditional risk factors, we found that calcium supplement use was significantly associated with a 30% increased risk of IPF (hazard ratio: 1.30; 95% confidence interval: 1.08, 1.57). Stratified analyses showed that sex modified the observed associations, and the adverse effect of calcium supplement use was stronger among males (P-interaction: 0.037). Moreover, there was a cumulative effect of genetic factors and calcium supplementation on the risk of incident IPF. Compared with calcium supplementation nonusers with low genetic risk, those with calcium supplementation and high genetic risk had the highest risk of IPF incidence (hazard ratio: 3.47; 95% CI: 2.59, 4.66).
Conclusions:
This study provides observational evidence that calcium supplementation may be a novel risk factor for IPF. Our findings highlight the importance of caution regarding the use of calcium supplements. Further experimental studies are still required to validate our results and elucidate the exact mechanisms.
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