Influence of Low-Intensity Pulsed Ultrasound Parameters on the Bone Mineral Density in Rat Model: A Systematic Review

Bone recovery typically depends on the age of organisms or the prevalence of metabolic disorders such as osteoporosis, which is a metabolic condition characterized by decreased bone strength and bone mineral density (BMD). Therefore, low-intensity pulsed ultrasound (LIPUS), a non-invasive method for osteogenic stimulation, presents promising results. However, heterogeneity in animal study designs is a typical characteristic. Hence, we conducted a systematic review to evaluate the effectiveness of LIPUS in the recovery of experimental bone defects using rat models. We examined the areal and volumetric BMD to identify LIPUS doses to be applied and evaluated the accuracy reported by previous studies.The Virtual Health Library regional portal, PubMed, Embase, EBSCOhost, Scopus and CAPES were reviewed for animal studies that compared fracture treatments based on LIPUS with sham or no treatments using rat models and reported BMD as an outcome. The tool provided by the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE) and the Collaborative Approach to Meta-Analysis and Review of Animal Data from Experimental Studies (CAMARADES) checklist were used to assess the bias and quality of such studies.Of the six studies reviewed, the most frequently used LIPUS dose had an ultrasonic frequency of 1.0 MHz, repetition rate of 0.1 kHz and pulse duration of 2000 μs. An intensity (ISATA) of 30 mW/cm2 was the most preferred for bone recovery. However, the BMD could not solely irrefutably evaluate the effectiveness of LIPUS in bone recovery as the results were discordant with each other. The discrepancies in experimental methodologies, low-quality classifications and high risk of bias in the selected studies, however, did not validate the undertaking of a meta-analysis.On the basis of the BMD results, no sufficient evidence was found to recommend the use of LIPUS for bone recovery in rat models. Thus, this systematic review indicates that the accuracy of such reports must be improved to improve their scientific quality to facilitate a transition of LIPUS applications from pre-clinical research to clinic use.