Osteochondrosis and osteomalacia are distinguished by inflammatory factors and metabolites

Both osteochondrosis and osteomalacia are metabolic disorders that are impacted by a combination of genetic and environmental factors. The objective of this research is to explore the potential causal connection between plasma metabolomics and the development of osteochondrosis and osteomalacia, with a focus on inflammatory factors. Summary statistics were collected for 91 inflammatory cytokine traits, 1400 plasma metabolite traits, and osteochondrosis and osteomalacia traits from publicly accessible genome-wide association studies. Causality was evaluated through two-sample Mendelian randomization analyses, which included methods such as inverse variance weighting, Mendelian randomization-Egger, weighted median, weighted mode, and simple mode analyses. Extensive sensitivity analyses were conducted to evaluate the reliability, diversity, and identification of horizontal pleiotropy in the results. The results of our study indicate that 4 cytokines play a significant causal role in osteochondrosis: C-X-C motif chemokine 5 ( P  = .029, OR = 0.864, 95% CI = 0.758–0.985), interleukin-20 receptor subunit alpha ( P  = .041, OR = 1.244, 95% CI = 1.009–1.534), interleukin-33 ( P  = .009, OR = 0.786, 95% CI = 0.657–0.941), and macrophage inflammatory protein 1a ( P  = .021, OR = 0.829, 95% CI = 0.707–0.971). Furthermore, we identified an association between inflammatory cytokines and osteomalacia, specifically with tumor necrosis factor receptor superfamily member 9 ( P  = .010, OR = 1.820, 95% CI = 1.157–2.863). Subsequent screening of metabolites related to osteochondral (X-12798 levels, P  = 9.95E‐05) and osteomalacia (adenosine 5′-monophosphate to glutamate ratio, P  = 1.27E‐04) was conducted based on these inflammatory factors. The research indicates that IL-33, CXCL5, IL-20RA, and MIP-1α could potentially play crucial roles as upstream factors influencing the development of osteochondrosis, while metabolites like X-12798 may serve as promising biomarkers in this context. Furthermore, TNFRSF9 is suggested as an upstream determinant of osteomalacia, with the AMP to glutamate ratio identified as a potential biomarker. These results underscore the importance of utilizing these cytokines and metabolites in clinical practice for distinguishing between osteochondrosis and osteomalacia, as well as for exploring potential therapeutic interventions.