Short-course systemic salidroside increases week-4 tibial implant fixation strength in healthy female mice: A proof-of-concept study

Source abstract

Background Rapid early osseointegration is essential for cementless fixation, yet this postoperative window is vulnerable in metaphyseal cancellous bone exposed to surgical injury and early loading. Salidroside, a bioactive glycoside derived from Rhodiola species, has reported osteogenic and angiogenic activity, but its value as a short-course systemic perioperative adjuvant for implant fixation remains unclear. Methods Thirty-eight healthy 15-week-old female C57BL/6 mice underwent unilateral press-fit titanium implant insertion into the proximal tibia and were then randomized to intraperitoneal salidroside (20 mg/kg every other day) or volume-matched saline. The primary outcome in this report was week-4 maximum pull-out force. Ex vivo micro-computed tomography (micro-CT) assessed five parameters in peri-implant and distal metaphyseal cancellous regions. Histology and week-2 immunostaining were supportive tissue-context assessments. Results At week 4, maximum pull-out force was 20.68 ± 3.06 N with salidroside and 13.01 ± 1.77 N with saline (mean difference, 7.67 N; Welch 95% confidence interval [CI], 3.86 to 11.48; p=0.0024). After Benjamini–Hochberg false-discovery-rate correction across 11 secondary or exploratory comparisons, BV/TV and connectivity density were higher and trabecular separation was lower in both cancellous regions (all q≤0.05). The peri-implant trabecular-number difference was not statistically significant (p=0.0626; q=0.0861), and trabecular thickness did not differ. Week-2 HIF-1α integrated optical density did not meet the FDR threshold in the Welch analysis (p=0.0500; q=0.0786) and was also nonsignificant in the exact Mann–Whitney sensitivity analysis (p=0.1000); it was therefore treated as supportive only. Conclusions In healthy 15-week-old female mice, this specific intermittent salidroside regimen increased week-4 implant fixation strength and was accompanied by concordant exploratory micro-CT findings, providing a screening-level proof-of-concept efficacy signal. The study does not establish mechanism or efficacy in male, aged, osteoporotic, or comorbidity-affected hosts.