Bone Turnover Markers as Biomarkers of Cough Dysfunction and Respiratory Risk in Subacute Ischemic Stroke

Background/Objectives: Peak cough flow (PCF) is an objective measure of cough effectiveness after stroke, but biomarkers reflecting physiological vulnerability related to reduced PCF are not well established. We investigated whether bone turnover markers (BTMs)-C-terminal telopeptide of type I collagen (CTX) and procollagen type 1 N-terminal propeptide (P1NP)-were associated with PCF in subacute ischemic stroke. Methods: In this retrospective study, 112 patients admitted within 21 days of stroke onset had fasting morning CTX and P1NP measured by electrochemiluminescence immunoassay, and PCF measured within 72 h of admission. Associations were assessed using Spearman correlation and multivariable linear regression with BTMs standardized (per 1 standard deviation increase), adjusting for age, sex, body mass index, onset-to-admission days, National Institutes of Health Stroke Scale score, Korean version of the Modified Barthel Index, estimated glomerular filtration rate, smoking status, and brainstem lesion. Results: CTX showed an inverse correlation with PCF (rho = -0.469; p < 0.001) and remained independently associated with lower PCF after multivariable adjustment (β = -42.32 L/min; 95% confidence interval, -56.12 to -28.52; p < 0.001), whereas P1NP showed weaker associations. In secondary outcome analyses, higher CTX was associated with low PCF (PCF < 160 L/min), aspiration pneumonia, and longer length of stay. Conclusions: Higher CTX levels were independently associated with lower peak cough flow and selected respiratory-related outcomes in this retrospective cohort. These findings are hypothesis-generating, do not imply prognostic validation, and warrant confirmation in prospective multicenter studies assessing incremental predictive value.