Causal effect between systemic inflammatory cytokines and osteoporotic pathological fractures: A bidirectional Mendelian randomization study.
This study reveals a complex relationship between inflammatory factors and osteoporotic fractures, highlighting the potential for further research into their interactions.
Where it sits
this study against the rest of the thymulin (facteur thymique serique) corpusSummary and findings
This study investigates the causal relationship between systemic inflammatory cytokines and osteoporotic pathological fractures using a bidirectional Mendelian randomization approach. It analyzed data from 1,822 osteoporosis cases and 311,210 controls. The study identified several inflammatory factors associated with fracture risk.
Abstract
Osteoporosis is a prevalent metabolic bone disorder that significantly impairs patients' quality of life. Mounting evidence suggests a close relationship between systemic inflammation and bone metabolism, yet the causal nature of this association remains unclear. This study aims to elucidate potential causal links between circulating inflammatory factors and osteoporotic pathological fractures. We employed a bidirectional 2-sample Mendelian randomization (MR) approach, utilizing large-scale genetic data from the FinnGen biobank (1822 osteoporosis cases and 3,11,210 controls) and the genome-wide association study catalog to analyze 91 circulating inflammatory factors. Instrumental variables were selected using a threshold of P < 1 × 10-5, followed by stringent linkage disequilibrium pruning (R2 < 0.001). The inverse variance weighted method served as the primary analytical tool, supplemented by MR-Egger, weighted median, and mode-based estimator methods. Sensitivity analyses, including leave-one-out analysis, Mendelian Randomization Pleiotropy RESidual Sum and Outlier, and Cochran's Q test, were conducted to assess the robustness of the results. Forward MR analysis identified potential causal associations between 7 inflammatory factors and the risk of osteoporotic pathological fractures. Notably, Artemin levels were negatively correlated with fracture risk (OR = 0.7954, P = .0167), while elevated levels of β-nerve growth factor (OR = 1.2375, P = .0398), C-X-C motif chemokine 10 (OR = 1.2675, P = .0183), CXCL6 (OR = 1.2623, P = .0026), interleukin-10 receptor α subunit (OR = 1.2828, P = .0204), interleukin-10 receptor β subunit (OR = 1.1463, P = .0386), and latency-associated peptide transforming growth factor β1 (OR = 1.2481, P = .0206) were associated with increased fracture risk. Reverse MR analysis suggested that fractures might lead to decreased levels of C-X-C motif chemokine 11 (OR = 0.9574, P = .0104), interleukin-1α (OR = 0.9591, P = .0263), and thymic stromal lymphopoietin (OR = 0.9625, P = .0439), as well as elevated levels of tumor necrosis factor-β (OR = 1.0519, P = .0111). This study unveils a complex bidirectional relationship between circulating inflammatory factors and osteoporotic pathological fractures. These findings provide novel insights into the pathogenesis of osteoporosis and offer important clues for potential preventive, diagnostic, and therapeutic strategies.
Background
The paper addresses the relationship between systemic inflammatory cytokines and osteoporotic fractures, a significant concern in aging populations. Prior research has suggested that inflammation may play a role in bone health, but causality remains unclear. This study aims to clarify whether elevated cytokine levels are a risk factor for fractures, which could inform future preventive strategies.
Methods
The study employed a bidirectional Mendelian randomization design, utilizing genetic variants as instrumental variables to assess the causal effects of cytokines on fracture risk and vice versa. The specific population, sample size, doses, and duration of exposure are not reported in the abstract.
Results
Not reported in abstract.
Interpretation
The findings, if significant, would contribute to understanding the role of inflammation in bone health. However, without specific numeric results, it is challenging to assess the clinical significance of the observed relationships. Potential confounds include the reliance on genetic variants and the absence of direct clinical data.
Key findings
- Not reported in abstract.
Limitations
- Not reported in abstract.