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Causal relationship between aging-related biomarkers and osteoporosis: A bidirectional two-sample Mendelian
Rui Xu1,2, Yin Sun1,2, Gui-Guo Xu1,2
1Department of Orthopedics, The First People's Hospital of Yunnan Province & The Affiliated Hospital of Kunming University of Science and Technology, China.
The Journal of International Medical Research
|July 30, 2026
Summary
This study found no strong causal links between eight aging biomarkers and osteoporosis risk in Europeans. Further research is needed for insulin-like growth factor 1, isoleucine, and Dickkopf-related protein 1.
Area of Science:
- Genetics
- Biomarkers
- Osteoporosis Research
Background:
- The relationship between biological aging markers and osteoporosis is not fully understood.
- Identifying causal factors for osteoporosis is crucial for prevention and treatment.
Purpose of the Study:
- To investigate potential causal associations between genetically predicted aging biomarkers and osteoporosis risk.
- To evaluate eight aging-related traits, including telomere length and specific metabolites, in relation to osteoporosis.
Main Methods:
- Utilized a bidirectional two-sample Mendelian randomization analysis in a European population.
- Employed inverse-variance weighted methods, supplemented by sensitivity analyses to ensure robustness.
- Assessed potential pleiotropy and heterogeneity using established statistical tests.
Main Results:
- Nominal associations were observed for insulin-like growth factor 1 and isoleucine with lower osteoporosis risk, and Dickkopf-related protein 1 with higher risk.
- These associations did not withstand Bonferroni correction, indicating a lack of robust evidence.
- Sensitivity analyses suggested a significant association for Dickkopf-related protein 1, but no other biomarkers showed significant causal effects.
Conclusions:
- No definitive causal effects were established between the eight aging biomarkers and osteoporosis in the studied population.
- Observed nominal associations for insulin-like growth factor 1, isoleucine, and Dickkopf-related protein 1 warrant further investigation.
- The aging-skeleton axis requires additional research to clarify potential molecular links.
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