Depression and Osteoporosis: A Mendelian Randomization Study
Open accessAbstract
Observational studies suggest a link between depression and osteoporosis, but these may be subject to confounding and reverse causality. In this two-sample Mendelian randomization analysis, we included the large meta-analysis of genome-wide association studies for depression among 807,553 individuals (246,363 cases and 561,190 controls) of European descent, the large meta-analysis to identify genetic variants associated with femoral neck bone mineral density (FN-BMD), forearm BMD (FA-BMD) and lumbar spine BMD (LS-BMD) among 53,236 individuals of European ancestry, and the GWAS summary data of heel BMD (HE-BMD) and fracture among 426,824 individuals of European ancestry. The results revealed that genetic predisposition towards depression showed no causal effect on FA-BMD (beta-estimate: 0.091, 95% confidence interval [CI] − 0.088 to 0.269, SE:0.091, P value = 0.320), FN-BMD (beta-estimate: 0.066, 95% CI − 0.016 to 0.148, SE:0.042, P value = 0.113), LS-BMD (beta-estimate: 0.074, 95% CI − 0.029 to 0.177, SE:0.052, P value = 0.159), HE-BMD (beta-estimate: 0.009, 95% CI − 0.043 to 0.061, SE:0.027, P value = 0.727), or fracture (beta-estimate: 0.008, 95% CI − 0.071 to 0.087, SE:0.041, P value = 0.844). These results were also confirmed by multiple sensitivity analyses. Contrary to the findings of observational studies, our results do not reveal a causal role of depression in osteoporosis or fracture.
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MDD is associated with poor bone health.
“A growing body of evidence shows that MDD is associated with poor bone health106-109.”
From Comorbidity between major depressive disorder and physical diseases: a comprehensive review of epidemiology, mechanisms and management (2023) · cites this paper as [108]
The Introduction and Discussion report that some meta-analyses found depression associated with low bone mineral density and fracture risk. But they also describe the observational findings as inconsistent, and the paper’s own Mendelian randomization analysis found no evidence of a causal effect. The unqualified claim omits those limitations; it does not itself claim causation. (LLM, conf=0.82)
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- Authors
- He, B., Lyu, Q., Yin, L., Zhang, M., Quan, Z., & Ou, Y.
- Affiliations
- The Affiliated Yongchuan Hospital of Chongqing Medical University (CN)
- Corresponding author
- He, Bin
- Venue
- Calcified Tissue International
- Published
- 2021-07-14
- Volume
- 109
- Issue
- 6
- Pages
- 675-684
- ISSN
- 0171-967X (ISSN-L)
- 1432-0827
- PMC
- PMC8531056
- OpenAlex
- W3178675869
- Cited by
- 44
- References
- 48
- Citations by year
- 2026: 5 · 2025: 6 · 2024: 12 · 2023: 9 · 2022: 9 · 2021: 3
- FWCI
- 8.13
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Calcified Tissue International (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Natural Science Foundation of Chongqing (cstc2019jcyj-msxmX0836)
- national natural science foundation of china (81701382)
- Topics
- Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Keywords
- depression, osteoporosis, bone mineral density, fracture risk, causal inference, genetic variants, femoral neck, forearm, lumbar spine, heel, reverse causality, confounding
- MeSH terms
- Depression, Humans, Osteoporosis, Bone Density, Polymorphism, Single Nucleotide, Genome-Wide Association Study, Mendelian Randomization Analysis
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