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

Abstract

BackgroundRapid 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.MethodsThirty-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.ResultsAt 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.ConclusionsIn 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.