Background and Objectives: In this review, we have explored the relationship between overtraining syndrome (OTS) and bone stress injuries among paralympic athletes. OTS is a complex condition that arises from an imbalance between training volume, nutrition, and recovery time, leading to significant negative effects on paralympic athlete’s performance and overall well-being. On the other hand, bone stress injuries occur when abnormal and repetitive loading is applied to normal bone, resulting in microdamage accumulation and potential. The prevalence of overtraining syndrome and bone stress injuries among athletes highlights the need for a better understanding of their relationship and implications for prevention and management strategies. Methods: A literature review from the PubMed, Web of Science, and Google Scholar databases including the MeSH keywords “overtraining syndrome”, “bone”, and “paralympic athletes”. Results: Studies have consistently shown that athletes engaged in endurance sports are particularly susceptible to overtraining syndrome. The multifactorial nature of this condition involves not only physical factors, but also psychological and environmental determinants. In addition, the diagnosis and management of OTS and bone stress injuries present challenges in clinical practice. Conclusions: Currently, there are no definitive biochemical markers for overtraining syndrome. The diagnosis is based on a combination of subjective measures such as questionnaires, symptoms checklists, and objective biomarkers, including hormone levels, inflammatory markers, and imaging studies. However, these diagnostic approaches have limitations regarding their specificity and sensitivity.

Conventional measures such as maximal oxygen uptake ($\dot{\mathrm{V}}$O₂max), although widely regarded as the gold standard, do not fully capture endurance performance. Therefore, this study investigated whether a 2.4 km Cooper test elicits measurable changes in blood-based biomarkers (decorin, hypoxanthine, N-terminal pro-B-type natriuretic peptide (NT-proBNP), brain-derived neurotrophic factor (BDNF)) and whether integrating these markers may improve performance prediction in a heterogeneous sample of runners. In this cross-sectional observational proof-of-concept study, thirty-three participants completed the 2.4 km Cooper test, with venous blood samples collected at baseline and post-test. Non-parametric statistical tests were used to assess biomarker changes (α = 0.05), with exploratory correlations evaluated using Spearman’s ρ. To examine whether blood-based biomarkers provide information beyond conventional field-based predictors, Ridge regression with leave-one-out cross-validation (LOOCV) was applied to predict 10 km race time in a subsample of 24 participants who completed a 10 km race two weeks later. The Cooper test elicited significant post-test changes in decorin, hypoxanthine, and BDNF (all p < 0.001). Higher post-test decorin (ρ = −0.44, p = 0.010) and hypoxanthine (ρ = −0.37, p = 0.034) were associated with faster Cooper test performance. In Ridge regression analysis, adding post-test decorin to conventional predictors resulted in a minor reduction of 10 km race time prediction error. This study suggests that decorin may provide complementary information to a conventional field-based test in heterogeneous recreational runners. Post-test decorin marginally contributed to 10 km race performance prediction beyond established predictors, though external validation and comparison with directly measured $\dot{\mathrm{V}}$O₂max are needed before practical application can be recommended.

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