Therapeutic Modulation of Glucocorticoid-Induced Sarcopenia by Boron: A Multimodal Preclinical Assessment

Boron is a bioactive trace element with emerging roles in musculoskeletal homeostasis and reported antioxidant, anti-inflammatory, and cytoprotective properties. These biological activities make boron a potential candidate for targeting the multifactorial processes underlying skeletal muscle deterioration. Sarcopenia, characterized by progressive loss of muscle mass and function, remains a major therapeutic challenge, with no pharmacological treatment currently established specifically for restoring sarcopenia-related muscle loss and functional impairment. This unmet therapeutic need is particularly relevant to glucocorticoid-induced muscle wasting, a clinically important adverse consequence of prolonged glucocorticoid exposure. Despite its biological properties, the therapeutic potential of boron in glucocorticoid-induced sarcopenia remains largely unexplored. Therefore, this study investigated whether boron supplementation could promote functional and structural muscle recovery in a dexamethasone (DEX)-induced sarcopenia model in female Sprague–Dawley rats for the first time. After administering DEX (1 mg/kg/day, intraperitoneally) for 14 days, boron was given via drinking water at concentrations of 50 or 100 mg/L for 28 days. Muscle function was assessed through forelimb grip strength and hanging grid tests. The preservation of skeletal muscle was further evaluated with MRI, histopathological analysis, and muscle weight measurements. We also analyzed organ weights, serum biochemical parameters, and blood indices to assess systemic safety. Boron supplementation promoted functional and structural recovery following DEX-induced skeletal muscle wasting. By Day 42, forelimb grip strength was approximately 84–94% higher in boron-treated animals than in the untreated sarcopenia model (~ 6.5–6.8 vs. ~3.5 kgf), accompanied by greater preservation of skeletal muscle volume on MRI. Consistent with these functional and imaging findings, histopathological assessment demonstrated a dose-dependent attenuation of muscle atrophy, with atrophy scores reduced by approximately 50% and 80% following treatment with 50 and 100 mg/L boron, respectively ( p = 0.014 and p < 0.001 vs. the sarcopenia model). Importantly, boron treatment was not associated with overt adverse changes in major organ weights or the evaluated biochemical and hematological parameters, indicating favorable systemic tolerability under the experimental conditions. Collectively, these findings provide preclinical evidence that boron supplementation may promote functional and structural recovery following DEX-induced skeletal muscle wasting and support further mechanistic and translational investigation.