Causal relationship between immune cells and bone metabolic diseases: a Mendelian randomization analysis of European populations in international databases

doi:10.12307/2025.760

Abstract

Abstract: BACKGROUND: Immune cells are correlated with various metabolic bone diseases, yet the specific immunological mechanisms and causal relationships remain elusive.
OBJECTIVE: To investigate the causal relationship between immune cells and the risk of metabolic bone diseases through two-sample Mendelian randomization.
METHODS: Genome-wide association study (GWAS) data on 731 immune cells and metabolic bone diseases (osteonecrosis, osteomalacia, osteoporosis, and osteoporosis combined with pathological fracture) were obtained from publicly available databases. Genetic variants related to immune cells were employed as instrumental variables. The inverse variance weighting method was utilized as the primary analytical approach, while MR-Egger and weighted median methods were applied to assess the causal relationships between immune cells and the risk of metabolic bone diseases. In addition, MR-PRESSO, MR-Egger regression, Cochran’s Q test, and the leave-one-out method were implemented to evaluate genetic polymorphisms and the heterogeneity of instrumental variables, and MR Steiger method was used to exclude reverse causality.
RESULTS AND CONCLUSION: (1) The analysis revealed that IgD- CD38dim%B cells, HLA DR on CD14+ CD16- monocytes, and HLA DR on CD14+ monocytes were significantly and causally associated with an increased risk of osteoporosis (P < 6.8×10-5). Sensitivity analyses confirmed the reliability and stability of these results. Furthermore, among the immune cell types studied, 28 demonstrated potential causal associations with osteonecrosis, 23 with osteomalacia, 46 with osteoporosis, and 45 with the combined condition of osteoporosis and pathologic fracture (P < 0.05). (2) This study provides a comprehensive assessment of the causal influence of immune cells on metabolic bone diseases, highlighting the significant role of immune factors in the pathogenesis of these conditions, particularly osteoporosis. The findings contribute valuable insights into the relationship between immune traits and bone metabolism, laying a foundation for future research in this domain. This study utilized an international database to analyze the European population, which offers a reference for Chinese biomedical research in the realm of metabolic bone diseases, and facilitates the conduction of relevant studies for the Chinese population, thereby promoting the enhancement of the prevention and treatment of metabolic bone diseases.

Key words: immune cells, Mendelian randomization, osteoporosis, osteomalacia, pathological fracture, osteonecrosis, engineered tissue construction

CLC Number:

Chen Tianxin, , Zhang Zhilong, Zhang Shuai, Gao Yun, Zhu Yuqi, Yang Shengping. Causal relationship between immune cells and bone metabolic diseases: a Mendelian randomization analysis of European populations in international databases[J]. Chinese Journal of Tissue Engineering Research, 2025, 29(29): 6326-6332.

Figures/Tables 3

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