Identification of effective vibration parameters for enhancing bone response in small rodents: A systematic review...

Low-intensity vibration (LIV) is a non-invasive mechanical stimulus capable of regulating skeletal adaptation and bone remodeling cellular signaling pathways. Despite growing interest in LIV, substantial methodological heterogeneity persists in the experimental vibration parameters. This study sought to synthesize the effects of different LIV frequencies and intensities on bone volume fraction (BV/TV) in small rodent models. We performed a systematic review searching for publications in English on PubMed, Web of Science, CINAHL, and Embase databases. Two independent investigators followed inclusion criteria to select peer-reviewed studies with mature mice and rats, using whole-body vibration experiments without other co-variables. In addition to these core criteria, a detailed hierarchical screening framework was applied for full-text review. We used Bayesian network meta-analysis (NMA) and SYRCLE risk of bias (RoB) to assess the selected studies. For tibia, NMA found 45 Hz at 2 g₀ (estimated effect 3.22 [CrI 1.98, 4.45]), 45 Hz at 0.2 g₀ (estimated effect 2.32 [CrI 1.01, 3.62]) and 90 Hz at 1 g₀ (estimated effect 0.25 [CrI -2.70, 3.26]) as the top three candidates. For femur, NMA identified 90 Hz at 1.4 g₀ (estimated effect 3.08 [CrI -1.99, 7.97]), 45 Hz at 2 g₀ (estimated effect 1.25 [CrI -1.48, 3.86]), and 45 Hz at 0.2 g₀ (estimated effect 1.18 [CrI -1.54, 3.80]) as the regimes with the highest chances to increase trabecular BV/TV. To evaluate a common top performing regimen for both tibia and femur we exposed 5-month-old male C57BL/6 for 4 weeks (n = 10/group) to a 45 Hz at 0.2 g₀ LIV regimen. When comparing pre- and post-LIV measurements within each bone, 9 out 18 μCT variables evaluated showed significant changes in the femur, and 5 variables within tibia with two-way ANOVA identifying a greater response in the femur. These findings support NMA as a useful tool for prioritizing LIV regimens in small rodents. Although several μCT measures showed greater femoral responses experimentally, which was not predicted by NMA, LIV effects in both bones fell within the NMA's 95% credible intervals, supporting 45 Hz/0.2 g₀ as a promising regimen for both the tibia and femur.