ArticlePloS one2023
The associations of alcoholic liver disease and nonalcoholic fatty liver disease with bone mineral density and the mediation of serum 25-Hydroxyvitamin D: A bidirectional and two-step Mendelian randomization.
Article in PloS one, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 9 citations in OpenAlex.
- The Liver-Bone Axis in Steatotic Liver Disease.Calcified tissue international · 2026Review
- PHEWAS, TWAS, Mendelian Randomization in Osteoporosis Research: the good, the bad, and the ugly.Current osteoporosis reports · 2026Review
- Prospects of Mendelian randomization in hepatology: a comprehensive literature review with practice guidance.Clinical and molecular hepatology · 2025Review
- Review
- Association between gestational diabetes mellitus and offspring health: a two-sample mendelian randomization study.BMC pregnancy and childbirth · 2025Article
- Mechanisms and therapeutic strategies linking mesenchymal stem cells senescence to osteoporosis.Frontiers in endocrinology · 2025Review
- Association between nonalcoholic fatty liver disease and bone mineral density: Mendelian randomization and mediation analysis.Bone reports · 2024Article
- Genetic evidence of the causal relationship between chronic liver diseases and musculoskeletal disorders.Journal of translational medicine · 2024Article
Corrections and comments
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Authors and funding
5 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundReduced bone mineral density (BMD) and osteoporosis are common in chronic liver diseases. However, the causal effect of alcoholic liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD) on BMD remains uncertain.
objectivesThis study uses a two-sample Mendelian randomization (MR) design to evaluate the genetically predicted effect of ALD and NAFLD on BMDs using summary data from publically available genome-wide association studies (GWASs).
methodsThe GWAS summary statistics of ALD (1416 cases and 213,592 controls) and NAFLD (894 cases and 217,898 controls) were obtained from the FinnGen consortium. BMDs of four sites (total body, n = 56,284; femoral neck, n = 32,735; lumbar spine, n = 28,498; forearm, n = 8143) were from the GEnetic Factors for OSteoporosis Consortium. Data for alcohol consumption (n = 112,117) and smoking (n = 33,299) and serum 25-Hydroxyvitamin D (25-OHD) level (n = 417,580) were from UK-biobank. We first performed univariate MR analysis with the Inverse Variance Weighted (IVW) method as the primary analysis to investigate the genetically predicted effect of ALD or NAFLD on BMD. Then, multivariate MR and mediation analysis were performed to identify whether the effect was mediated by alcohol consumption, smoking, or serum 25-OHD level.
resultsThe MR results suggested a robust genetically predicted effect of ALD on reduced BMD in the femoral neck (FN-BMD) (IVW beta = -0.0288; 95% CI: -0.0488, -0.00871; P = 0.00494) but not the other three sites. Serum 25-OHD level exhibited a significant mediating effect on the association between ALD and reduced FN-BMD albeit the proportion of mediation was mild (2.21%). No significant effects of NAFLD, alcohol consumption, or smoking on BMD in four sites, or reverse effect of BMD on ALD or NAFLD were detected.
conclusionOur findings confirm the genetically predicted effect of ALD on reduced FN-BMD, and highlight the importance of periodic BMD and serum 25-OHD monitoring and vitamin D supplementation as needed in patients with ALD. Future research is required to validate our results and investigate the probable underlying mechanisms.
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