Abstract Objective: To investigate the effect of acute high-altitude hypoxia exposure on bone metabolic balance by establishing a rat model of simulated acute high-altitude hypoxia, and to determine whether it induces high-turnover bone metabolic disorder and its early characteristics. Methods: Twelve healthy male Sprague-Dawley rats were randomly divided into a normoxic control group and a hypoxia exposure group (n = 6). The hypoxia group was placed in a hypobaric hypoxia chamber simulating an altitude of 8000 meters (FiO? ≈ 8%) for 12 hours, while the control group was housed under normobaric normoxic conditions for the same period. After exposure, blood samples were collected, and red blood cell count (RBC), hemoglobin concentration (HGB), and hematocrit (HCT) were measured using an automated hematology analyzer to assess the hypoxic stress response. Diastolic interventricular septum thickness (IVSTd), left ventricular posterior wall thickness (LVPWT), and left ventricular end-diastolic diameter (LVEDD) were detected using a high-frequency small animal ultrasound system to comprehensively evaluate the establishment of the acute hypoxia model. Serum bone metabolic markers, including bone formation markers osteocalcin (OC) and procollagen type I N-terminal propeptide (P1NP), as well as bone resorption markers β-cross-linked C-telopeptide of type I collagen (β-CTX) and tartrate-resistant acid phosphatase (TRAP), were measured by enzyme-linked immunosorbent assay (ELISA). Results: Compared with the normoxic control group, RBC, HGB, and HCT in the hypoxia group were significantly increased（P＜0.05）. Cardiac ultrasound revealed increased IVSTd and LVPWT, and decreased LVEDD in the hypoxia group, consistent with early myocardial hypertrophy changes induced by acute hypoxic stress. After hypoxia exposure, serum levels of bone formation markers OC and P1NP in the hypoxia group were significantly decreased by 27% and 21%（P＜0.01）, respectively, while serum levels of bone resorption markers β-CTX and TRAP were significantly increased by 28% and 20%（P＜0.01）, respectively, compared with the control group. Conclusion: Acute hypoxia exposure can inhibit bone formation and promote bone resorption, leading to high-turnover bone metabolic disorder, indicating that the bone metabolic system is highly sensitive to hypoxic stress.