Low-intensity pulsed ultrasound in acute multiple rib fracture—a prospective analysis, randomized controlled trial and pilot study

Introduction

Low-intensity pulsed ultrasound (LIPUS), introduced by Xavier and Duarte in 1983, promotes bone healing through low-intensity (<3 W/cm²), pulsed wave stimulation. Approved by the Food and Drug Administration (FDA) in 1994 for fresh fractures and in 2000 for nonunions, LIPUS has demonstrated therapeutic efficacy in enhancing bone regeneration. These established principles can be effectively applied to managing acute multiple rib fractures (MRFs) (1-4). Fractures present a prevalent clinical scenario, with over a million new cases reported annually, even in the United Kingdom (5). Although traditional medical methods have historically managed effectively the healing process of fractures, recent findings by Zura et al. suggest a failure rate of approximately 4.9% in healing and union out of 309,330 patients with fractures (6). Such treatment failures can cause considerable distress for patients, leading to significant delays in their return to daily activities, social engagements, and work, thereby not only affecting the individual but also resulting in substantial socio-economic losses. Nonunion and similar conditions are typically defined when normal healing processes are not completed within nine months post-injury. Throughout this healing period, successful fracture recovery requires well-coordinated processes, commencing with effective fixation, followed by appropriate reduction and stabilization of the fractured site, thereby providing the necessary stimulus for the generation of new bone and cartilage (7). In the realm of fracture healing principles, Giannoudis and colleagues have encapsulated them in what they term the diamond concept. This concept suggests that, under normal circumstances, appropriate fixation of the fracture site, along with the assistance of growth factors and osteogenic cells, facilitates the gradual reduction of fracture ends (8). While the majority of fractures heal successfully following this ideal trajectory, some cases experience treatment failure, presenting significant challenges for clinical practitioners and causing considerable hardships for patients, leading to notable temporal and economic burdens. It is noteworthy that such nonunions are more frequently observed in patients with contributing factors such as smoking, diabetes, advanced age, and osteoporosis (9-12).

The incidence of rib fractures resulting from thoracic trauma ranges from 7% to 38.7%, with both morbidity and mortality rates correlating directly with the number of ribs fractured. Morbidity rates increase from 5.8% in cases involving a single rib fracture to approximately 34% when seven or more ribs are fractured (13,14). MRFs occur in about 10% of all trauma cases and up to 80% of severe thoracic injuries, identifying these patients as a high-risk group. Mortality rates in this cohort can reach as high as 33%, with the risk of mortality statistically doubling in patients over the age of 65 years (15-18). In clinical practice, rib fractures are indicative of severe bodily and solid organ damage. These fractures are frequently associated with other thoracic injuries and commonly co-occur with head, extremity, abdominal injuries, and blunt cardiac trauma (19,20). Multiple studies have demonstrated that the number of rib fractures is correlated with an increased risk of mortality and complications. Specifically, an increase in rib fractures is associated with heightened risks of death, pneumonia, acute respiratory distress syndrome (ARDS), pneumothorax, hemothorax, aspiration pneumonia, empyema, and prolonged hospital and intensive care unit (ICU) stays. Additionally, the number of rib fractures is also correlated with mortality, hypotension, and the Injury Severity Score (ISS) (21,22). The clinical significance of rib fracture location and pattern is emphasized by a study involving 1,495 patients from a single institution, which found that bilateral fractures and concurrent lung parenchymal injuries significantly increased the risk of mortality due to chest injuries (23). In another cohort of 1,490 patients with blunt chest trauma, mortality was associated with the presence of flail chest and the number of fractures (17). Flail chest alone was associated with a mortality rate of 16–17%, which increased to 42% when accompanied by pulmonary contusion. Additionally, a first rib fracture was linked to a 36% mortality rate and a high likelihood of concomitant injuries in one study (17,24-26). Rib fracture patients also frequently report severe pain, and effective, immediate pain management can enhance respiratory dynamics and reduce the incidence of respiratory and systemic complications, such as pneumonia, pulmonary effusion, ARDS, lobar collapse, and the need for mechanical ventilation. Recent studies have shown that 11% to 31% of patients with MRFs develop pneumonia, nearly quadrupling their mortality risk (14,19,27,28). Guidelines for managing blunt chest wall trauma typically prioritize advanced age and MRFs as key indicators for identifying high-risk patient populations. These patients should be admitted for further management, either to a general ward or an ICU. Recent studies have demonstrated ICU admission rates ranging from 63% to 73%, despite increases in both the age and severity of injuries within the cohort. Importantly, poor functional status has emerged as the strongest predictor of complications and prolonged hospital stays, more so than age or anatomical factors. Commonly cited factors in rib fracture scoring and triage systems include advanced age, a greater number of fractured ribs, chest wall instability, and significant non-traumatic comorbidities (15,19). ICU admission can benefit these high-risk patients by enabling effective pain management, aggressive pulmonary hygiene, and close monitoring for respiratory complications. However, overly sensitive ICU admission criteria may lead to the overutilization of resources and potentially expose patients to unnecessary iatrogenic complications (29). Current treatments for rib fractures generally involve three primary approaches: (I) pain control and/or surgical fixation, often with nonsteroidal anti-inflammatory drugs (NSAIDs) and opioids, to facilitate coughing, deep breathing, and participation in physiotherapy, thereby reducing the risks of pneumonia and mortality; (II) respiratory rehabilitation and exercise aimed at reducing various complications, particularly respiratory issues and pneumonia; and (III) early recovery of strength and movement to promote a smooth return to daily activities and work (30-34). However, treatment methods known to be clinically effective, such as surgical fixation and pharmacological interventions excluding conventional pain relievers, including thoracic epidural analgesia, paravertebral injections, and intercostal nerve blocks, are often invasive and associated with unforeseen complications. These approaches also demand significant medical and social resources and entail substantial costs. Moreover, there remains disagreement regarding the complete recovery and overall benefits of these treatments (35,36).

Ultrasonography is a non-invasive application of mechanical energy, utilizing high-pressure sound waves to penetrate from the skin into deeper tissues. This technique is widely used across various medical specialties due to its therapeutic benefits. Its effectiveness depends on precise adjustments of key parameters, including mode, frequency, intensity, and duration, owing to its dose-response mechanism. Ultrasonography is generally classified into two modes: continuous mode, which is primarily associated with thermal effects, and pulsed ultrasound (PUS) mode, which is linked to biological effects. As the pathology becomes more recent, a higher pulsed output is increasingly considered necessary. Therapeutic ultrasound typically operates within a frequency range of 0.75 to 3.3 MHz, with tissue penetration inversely related to frequency. For therapeutic efficacy, it is crucial to apply ultrasound at the lowest intensity to avoid tissue damage; intensities exceeding 0.5 watt/cm² are generally ineffective in acute conditions, while intensities in the range of 0.5 to 1.0 watt/cm² are stable for chronic conditions. In pulsed mode, the treatment duration depends on the injury’s extent. For acute injuries, treatments are typically administered once or twice a week, with the transducer moved at speeds below 4 cm/s, using circular or longitudinal stroking patterns and overlap (37,38). Recent studies have demonstrated that PUS, with its specific characteristics, enhances the consolidation of recent limb fractures, improving quality of life, reducing treatment costs, and expediting the return to daily and occupational activities (39,40). Hannemann et al. (41) reported significant radiological union in patients with acute fractures treated non-surgically using PUS. Lou et al. (42) endorsed PUS as a suitable treatment modality for acute fractures, while Leighton et al. (43) recommended it as an alternative for high-risk surgical candidates. Furthermore, several clinical trials have confirmed PUS as a stable and effective treatment for knee osteoarthritis. Additionally, recent experimental studies and randomized controlled trials have highlighted the effectiveness of PUS in reducing pain, minimizing disability, and accelerating healing in rib fractures (44-47). We present this article in accordance with the CONSORT reporting checklist (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2024-2136/rc).

Methods

All patients followed the established clinical protocol. Upon arrival at the outpatient clinic or emergency department, an initial evaluation was conducted, which included obtaining a basic medical history, performing a physical examination, and conducting initial imaging studies, such as chest X-rays and rib series. These evaluations were performed by a single cardiothoracic surgeon, trauma surgeon, and intensivist at a single medical center. If initial radiographic findings suggested MRFs, further confirmation was obtained through chest computed tomography (CT) with three-dimensional (3D) reconstruction. In cases where rib fractures were confirmed and LIPUS treatment was deemed necessary, chest wall ultrasono was utilized to precisely locate and mark the fractures identified by chest X-rays and CT scans. Finally, LIPUS treatment was administered to the marked areas.

Study protocols

This study was designed as a preliminary investigation to evaluate the application of LIPUS in the recovery of rib fractures. Rib fractures are a significant health concern, as they are among the most commonly observed fractures resulting from trauma (35). A prospective study design was employed to assess the efficacy of the LIPUS program in treating rib fractures. Initiated in April 2024 at a single medical center, the program was led by a single investigator and focused on acutely ill patients requiring appropriate management for rib fractures. The LIPUS program followed a structured protocol, consisting of the following procedures: (I) comprehensive history-taking and a meticulous physical examination; (II) basic imaging studies, including chest X-rays and rib series, which were compared with the patient’s history and physical examination findings to establish an initial diagnosis of rib fractures; (III) confirmation of the diagnosis via chest CT with 3D reconstruction, enabling the identification of the fracture’s location, number, pattern, and associated complications such as traumatic pneumothorax and hemothorax; (IV) precise anatomical localization for LIPUS (BH-3, ORYX Medical, Inc., Seoul, South Korea) administration was achieved using chest wall ultrasound with linear probe (Aplio400, Canon Medical, Inc., Otawara, Tochigi, Japan) to target the confirmed rib fractures; (V) LIPUS treatment was administered to the identified rib fractures. The LIPUS device is equipped with four probes, enabling the simultaneous treatment of up to four fractures. LIPUS therapy was applied to the four rib fracture sites identified as causing the most severe pain. Treatments were performed three times a week (Monday, Wednesday, and Friday), with each session lasting 15 minutes. The therapy utilized a pulse frequency of 1.5 MHz, a burst width of 200 microseconds, a pause width of 800 microseconds, a repetitive pulse frequency of 1.0 kHz, and a spatial average temporal average intensity of 30 mW/cm² of the LIPUS transducer’s surface area. The program was conducted from April 1, 2024 to October 31, 2024, and included 20 adult patients with MRFs, comprising 10 patients in the control group and 10 in the experimental group. Pain due to rib fractures was assessed using the Numeric Pain Rating Scale (NPRS) and the Visual Analog Scale (VAS). The NPRS is typically administered as an 11-point scale, either verbally or in written form, with anchors at 0 (no pain), 5 (moderate pain), and 10 (the worst imaginable pain or the worst pain ever experienced) (44).

Study subjects

Our hospitalization criteria for rib fractures include patients with severe injuries, such as involvement of more than three ribs, concurrent traumatic pneumothorax and/or hemothorax, multiple displaced fractures, or flail chest, as well as those exhibiting signs of significant respiratory compromise or those at risk of developing such compromise, whether they require general ward or ICU care. These criteria also encompass patients with inadequate pain control or respiratory issues, as evidenced by incentive spirometer (IS) volumes ≤8 mL/kg of ideal body weight (IBW), oxygen requirements ≥5 L/min via nasal cannula, a flail chest pattern, or those needing invasive or non-invasive positive pressure ventilation (NIPPV). For this study, the inclusion criteria comprised individuals aged 20 years or older who were admitted to the hospital with MRFs occurring within the previous seven days. The main exclusion criteria included individuals under 20 years of age and/or those with MRFs that had progressed beyond the acute phase (i.e., more than seven days post-injury). Furthermore, the primary exclusion criteria included patients who had undergone closed thoracostomy drainage for conditions such as traumatic hemothorax and/or pneumothorax. These patients were excluded to reduce bias resulting from secondary pain caused by chest tube insertion. Additionally, individuals requiring surgical interventions, such as rib fixation or thoracotomy exploration, were excluded to eliminate confounding variables associated with postoperative pain. Patients were randomly allocated into two groups by the Institutional Review Board (IRB) moderator, who was blinded to the study, using block randomization with blocks of four. The groups were as follows (1:1 ratio, 10 patients in each group): (I) the LIPUS group (n=10), which received treatment under the LIPUS program; and (II) the conventional group (n=10), which received standard rib fracture management and underwent the same probe placement procedure as the LIPUS group, did not receive any therapeutic ultrasound energy (Figure 1). Both the LIPUS and the conventional groups received appropriate and sufficient analgesia. Along with bed rest, early mobilization was actively promoted as part of the standard care protocol to reduce the risk of complications associated with prolonged immobility. To prevent respiratory complications, mucolytic agents were administered to aid sputum clearance, and structured respiratory care—including guided coughing and deep breathing exercises—was provided. In addition, daily chest posteroanterior or anteroposterior radiographs were performed to ensure early detection and prompt management of potential pulmonary complications. The analysis included assessments of clinical and demographic characteristics, clinical outcomes, and surgical complications. The primary aim of this study was to evaluate the impact of the LIPUS program on changes in pain control among patients.

Figure 1 Flowchart of the subjects who were enrolled, were allocated, completed the intervention, and were included in the analysis. LIPUS, low-intensity pulsed ultrasound.

Institution approval

The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the IRB of Konkuk University Chungju Hospital (IRB approval No. KUCH 2024-01-002). Prior to participation, all participants were provided with detailed information about the study’s objectives and procedures, and both verbal and written informed consent were obtained.

Statistical analysis

All statistical evaluations were carried out using MedCalc software for Windows, version 23.0.6 (MedCalc Software, Ostend, Belgium), while Microsoft Excel (Microsoft Corporation, Redmond, WA, USA) was utilized for data entry and initial processing. The distribution of continuous variables was examined using the Kolmogorov-Smirnov test to assess normality. For variables following a normal distribution, comparisons were made using Student’s t-test, and results were expressed as mean ± standard deviation. In contrast, non-normally distributed data were assessed using the Mann-Whitney U test and presented as median values with interquartile ranges (25th–75th percentiles). Categorical data were described using frequency counts and proportions, and comparisons between groups were analyzed via Pearson’s Chi-squared test or Fisher’s exact test as appropriate. When evaluating categorical variables in univariate analyses, either the Chi-squared or Fisher’s exact test was applied depending on the distribution characteristics. To control for multiple comparisons and reduce the likelihood of type I errors, Bonferroni post hoc adjustments were implemented by multiplying the number of comparisons by the corresponding P values. The Cox proportional hazards regression model was employed to identify factors independently associated with successful weaning, while overall survival estimates were generated using Kaplan-Meier survival analysis. Independent prognostic indicators for overall survival were also determined through the Cox regression model. Statistical significance was defined as a two-sided P value less than 0.05. To explore variables independently related to in-hospital mortality, both univariate and multivariate logistic regression analyses were conducted. A backward stepwise selection method was used for the multivariate model. Variables with a univariate P value <0.20, along with those considered clinically relevant, were entered into the multivariate regression as potential predictors. The model outputs included odds ratios (ORs), standard errors (SEs), 95% confidence intervals (CIs), and corresponding P values. To evaluate the discriminative performance of the logistic regression models, receiver operating characteristic (ROC) curves were constructed, and the area under the curve (AUC) was calculated. Model calibration was assessed using the Hosmer-Lemeshow goodness-of-fit test, which compared observed and expected outcomes across the range of predicted mortality risk. The AUC derived from the ROC curve was used to quantify model discrimination. Finally, Kaplan-Meier curves were plotted to depict cumulative survival over time, with group comparisons performed using the log-rank test.

Results

A total of 20 eligible cases (10 males, 10 females) were identified for analysis based on predefined criteria at our institution between April 1, 2024 and October 31, 2024. The demographic and clinical characteristics of the participants are summarized in Table 1 and Table S1, which presents a comprehensive comparison between the LIPUS and conventional treatment groups. Comparative demographic analysis revealed no significant differences between the groups in terms of age, sex, body weight, height, body mass index (BMI), obesity classification, or underlying medical conditions. Among the 20 patients (10 males and 10 females), 10 were assigned to the LIPUS group (5 males and 5 females), while 10 patients were categorized into the conventional management group (5 males and 5 females). The average age (43 to 84 years) was slightly lower in the LIPUS group compared to the conventional group, but the difference was not statistically significant (64.40±8.97 vs. 67.00±14.13 years, P=0.39). Baseline parameters were comparable across both groups, with no significant differences observed in sex distribution (5/5 vs. 5/5, P>0.99), body weight (66.35±11.66 vs. 69.33±11.11 kg, P=0.25), height (164.70±9.53 vs. 166.03±7.95 cm, P=0.50), body mass index (24.51±4.19 vs. 25.23±4.14 kg/m², P=0.44), injury mode (P=0.43) and underlying disease (P=0.75). Length of hospital stay was shorter in the LIPUS group, although this difference was not statistically significant compared to the conventional group (15.40±7.00 vs. 18.00±9.36 days, P=0.16). Similarly, no significant differences were observed between the groups in terms of hospital management, incidence of newly onset hemothorax and pneumothorax, atelectasis, or inflammation.

However, the Chest Trauma Score (CTS) was significantly higher in the LIPUS group, and the Thoracic Trauma Severity Score (TTSS) was also elevated, with both scores showing statistically significant differences when compared to the conventional group (7.80±1.74 vs. 5.70±0.79, P=0.001; 9.70±1.11 vs. 7.90±1.24, P=0.001, respectively). No instances of ICU transfer for further critical management or mortality during hospitalization were recorded in either group. No significant differences were found between the LIPUS and conventional groups regarding the total number of MRFs, the fracture site (anterior, lateral, and posterior regions), or the number of fractures in each region. Pain at the time of the initial hospital visit and immediately prior to the first LIPUS treatment was higher in the LIPUS group, although these differences were not statistically significant compared to the conventional group (7.62±2.08 vs. 7.40±1.37, P=0.57; 6.65±2.42 vs. 6.22±2.13, P=0.41, respectively). Following two sessions of LIPUS, significant pain improvement was observed in the LIPUS group, with statistical significance noted in all comparisons (3.77±1.37 vs. 5.28±2.04, P=0.001; 3.15±1.03 vs. 4.35±1.72, P=0.001; 2.67±0.97 vs. 3.75±1.53, P=0.001, respectively). These findings suggest that LIPUS may offer a more effective treatment approach than conventional management, even in patients with more severe conditions, as evidenced by higher CTS and TTSS (Figure 2). Repeated measures one-way analysis of variance (ANOVA) revealed no significant difference in pain scores between the LIPUS and conventional treatment groups (between-subjects effects, P=0.09). In contrast, the analysis revealed a highly significant reduction in pain with repeated LIPUS treatments (within-subjects effects, P=0.001). Moreover, when both the application of LIPUS and the time factor were analyzed concurrently, a significant interaction effect was observed, indicating further reductions in pain (group × factor interaction, P=0.001) (Table 2, Figure 3).

Figure 2 Case in real clinical practice. (A) An 81-year-old male sustained multiple rib fractures (6th to 10th ribs, right posterior; 7th to 10th ribs, posterolateral) and a right-sided traumatic hemothorax following a slip and fall during daily activities. His medical history includes diabetes mellitus, atrial fibrillation, and chronic kidney disease. Initial evaluation of the rib fractures and hemothorax was performed using chest CT with 3D reconstruction. The fracture sites are indicated by white arrows. (B) Initial evaluation of the rib fracture sites was performed using chest wall ultrasonography. The fracture sites are indicated by white arrows. (C) Marking of fracture sites on the thoracic wall skin was performed using chest wall ultrasonography, followed by real-field LIPUS treatment. 3D, three-dimensional; CT, computed tomography; LIPUS, low-intensity pulsed ultrasound.

Figure 3 Repeated measures one-way ANOVA, demonstrating significant difference in pain score levels between the LIPUS versus conventional groups [between-subjects effects, P=0.09; within-subjects effects, P=0.001; interaction between the group variable and the factor variable (group × factor interaction), P=0.001]. Repeated measures one-way ANOVA revealed no significant difference between groups in overall pain levels (between-subjects effect, P=0.09). However, both the within-subjects effect (P<0.001) and the group-by-time interaction (P=0.001) were statistically significant, indicating a differential trend in pain reduction over time between the groups. Pain scores prior to the third, fourth, and fifth treatment sessions were consistently lower in the LIPUS group compared to the conventional group. Specifically, the mean pain score before the third treatment was 3.77±1.37 in the LIPUS group versus 5.28±2.04 in the conventional group (P=0.001). Before the fourth treatment, scores were 3.15±1.03 and 4.35±1.72, respectively (P=0.001), and prior to the fifth session, 2.67±0.97 and 3.75±1.53, respectively (P=0.001). These findings demonstrate a significantly greater reduction in pain over time in the LIPUS group. ANOVA, analysis of variance; LIPUS, low-intensity pulsed ultrasound.

Discussion

LIPUS has been approved by the U.S. FDA since 1994 for promoting fracture healing, primarily through its non-thermal mechanisms, such as acoustic streaming and radiation force. Extensive clinical and preclinical studies have shown that LIPUS effectively accelerates the healing of fresh fractures, nonunions, and delayed unions when applied in pulse mode, irrespective of the device type or environmental factors. Beyond fracture healing, LIPUS has been utilized in various fields of physical therapy, including applications in the musculoskeletal and nervous systems, the prevention of muscle atrophy, dentofacial tissue regeneration, and the treatment of cavernous nerve injuries associated with erectile dysfunction, among other conditions. Unlike traditional pharmacological therapies and invasive procedures, LIPUS delivers pulsed acoustic waves to targeted regions in a non-invasive, well-tolerated manner, with minimal side effects. The therapeutic benefits of LIPUS are largely attributed to its non-thermal mechanisms, which encompass cavitation, acoustic streaming, and acoustic radiation force. Cavitation, occurring in liquid or liquid-like environments, is believed to enhance membrane permeability and stimulate cellular activation. Acoustic streaming, particularly micro-streaming, has been shown to affect diffusion rates and regulate processes such as protein synthesis, cellular secretion, and sonoporation. Acoustic radiation force, meanwhile, has demonstrated potential effects on the cardiovascular and nervous systems, further underscoring the versatility of LIPUS as a therapeutic modality. In the early stages of investigating the clinical effects of LIPUS, it was primarily utilized to promote tissue repair, demonstrating its ability to accelerate wound healing, reduce edema, and soften scar tissue. These therapeutic effects were partially attributed to LIPUS’s influence on the inflammatory phase of the repair process. To date, it has been shown to modulate inflammatory responses across a wide range of medical fields. Its underlying mechanism has been linked to alterations in cytokine levels and the regulation of key signaling pathways, underscoring its critical role in mediating tissue repair and facilitating the healing process (45,46).

Several studies collectively underscore the multifaceted benefits of LIPUS in fracture healing, highlighting its potential to enhance bone regeneration through both cellular and molecular mechanisms. The role of osteoblasts, which differentiate from mesenchymal stem cells (MSCs), is crucial in fracture healing, and they are key cell types involved in bone formation. These cells have been shown to express several inflammatory chemokines, including monocyte chemotactic protein 1 (MCP-1), macrophage-inflammatory protein (MIP)-1, regulated upon activation, normal T cell expressed and secreted (RANTES), and interleukin-8 (IL)-8. These inflammatory cytokines are critical for fracture healing and can be modulated by stimuli from LIPUS. LIPUS treatment decreased lipopolysaccharide (LPS)-induced elevation of pro-inflammatory cytokines [tumor necrosis factor-α (TNF-α) and IL-6] and activated caveolin-1. And the phosphorylation of p38 mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinase (ERK) was inhibited by LIPUS (47). In addition, osteoblasts promote the proliferation and differentiation of MSCs and osteoprogenitor cells, both of which are essential for bone remodeling. As key regulators of inflammation in bone tissue, osteoblasts can be influenced by LIPUS, which modulates the release of inflammatory cytokines. This modulation not only promotes fracture healing but also helps suppress inflammation in inflammatory bone diseases (45,47). It has been reported that chondrocytes, the cells responsible for cartilage, are highly mechanosensitive, indicating that they can respond to stimuli from LIPUS. This response has the potential to reduce inflammation in chondrocytes, thus protecting articular cartilage. Recently, Sahu et al. demonstrated that continuous low-intensity ultrasound could repair cartilage in a pro-inflammatory environment by inhibiting the activation of nuclear factor kappa B (NF-κB) induced by TNF-α, IL-1β in bovine osteochondral explants (48). In 2001, Azuma et al. (3) focused on the practical application of LIPUS in rat femoral fracture healing. Their study emphasized the acceleration of the healing process through the modulation of various cellular reactions within the fracture callus. This likely involved stimulation of osteoblast activity, enhanced angiogenesis, and improved cartilage and bone formation—all crucial processes for effective fracture repair. In 2006, Tang et al. (4) explored the molecular mechanisms through which ultrasound, including LIPUS, promotes bone formation. Their research investigated key signaling pathways such as integrin, focal adhesion kinase, phosphatidylinositol 3-kinase, and Akt, which are vital for regulating osteoblast function and bone remodeling. By elucidating these molecular pathways, the study provided valuable insights into the specific cellular processes modulated by LIPUS. In 2016, Harrison et al. (2) conducted a comprehensive analysis of the mode and mechanisms of LIPUS, exploring its complex cellular effects that contribute to fracture repair. Their investigation likely examined how LIPUS influences cellular proliferation, differentiation, and extracellular matrix synthesis at the fracture site, ultimately promoting bone regeneration. LIPUS-generated ultrasound waves penetrate soft tissues to reach the cortical bone, activating key biological processes in fracture healing, including angiogenesis (49), progenitor cell activation and differentiation (50,51), and callus mineralization and remodeling (47,52). These processes are known to activate general treatment mechanisms, inflammatory responses, and the formation of both soft and hard calluses. Particularly, when LIPUS is transmitted through soft tissues to bone, mechanical signals stimulate cells via integrin mechano-receptors, activating biochemical responses (53,54). These responses enhance fracture recovery by increasing cyclooxygenase-2 production and regulating the Rab 5-Rac1 pathway, which controls ultrasound-mediated endocytosis and cell motility, ultimately facilitating cell-matrix adhesions through vinculin (55,56). Ultimately, LIPUS facilitates the formation of focal adhesions and the extension and expression of syndecan-4 (56,57). The primary goal for medical professionals treating fractures is the complete restoration and healing of the broken bone. LIPUS has been shown to be an effective adjunctive therapy for patients with nonunions (58-60) and has also been reported as an accelerative treatment for recent fractures managed with closed reduction and cast immobilization (60-62). In recent years, multiple studies have demonstrated LIPUS’s potential to enhance fracture recovery, with at least eight high-quality studies reporting a success rate of approximately 80% in bone recovery and nonunion patients (56-64).

In this study, the authors employed a predictive system for MRFs to estimate the prognosis and clinical course of patients. Currently, there are no prospectively validated scoring systems or algorithms to determine the appropriate admission status or location (e.g., discharge, ICU, or ward admission) for patients with rib fractures. However, several existing scoring systems are designed to predict the likelihood of respiratory failure resulting from rib fractures (19,65). Common factors across most of these scoring systems include age over 65 years, the number of fractured ribs, and the presence of bilateral rib fractures. One such scoring system, the CTS, quantifies the severity of chest injury by allocating points to defined risk factors in order to predict the likelihood of respiratory failure and increased mortality. A CTS score exceeding four points indicates a high risk of respiratory complications (65). The scoring is as follows: individuals under 45 years receive 1 point; those aged 46 to 65 years receive 2 points; and those over 65 years receive 3 points. No points are awarded for the absence of pulmonary contusion; 1 point is assigned for a minor contusion in one lung, 2 points for minor contusions in both lungs, 3 points for a severe contusion in one lung, and 4 points for severe contusions in both lungs. Points are also awarded based on the number of rib fractures: 1 point for fewer than three rib fractures, 2 points for three to five rib fractures, 3 points for more than five rib fractures, and 2 points for bilateral rib fractures. Patients with a CTS of 5 or higher face a nearly fourfold increased risk of mortality compared to those with scores below 5, highlighting the consistent correlation between a higher CTS and poorer outcomes. Another system, the RibScore, is based on fracture patterns and predicts the likelihood of pneumonia, respiratory failure, and the need for tracheostomy (19). In the RibScore system, each risk factor—such as six or more fractured ribs, bilateral fractures, flail chest, three or more bicortical (displaced) fractures, a first rib fracture, and multisegmented fractures—is typically assigned one point. A total score above three is associated with an increased risk of respiratory failure. Additional points are added for more than five rib fractures (3 points) and for bilateral rib fractures (2 points). The TTSS is calculated using six parameters: PaO₂/FiO₂ ratio, rib fractures, lung contusion, pleural injury, and age (23). Detailed parameters CTS, RibScore, and TTSS are summarized in Table 3.

An intriguing finding from our study is that most participants exhibited clinically meaningful improvements in pain levels, regardless of whether they received LIPUS therapy. Upon discharge, many patients reported varying degrees of relief during their exit interviews, acknowledging that they had experienced some form of intervention and speculating that a potential placebo effect might have contributed. Typically, the management of patients with MRFs primarily involves bed rest and observation. However, the incorporation of LIPUS into the treatment protocol introduced an additional active treatment component. This was perceived by patients as a more proactive approach to care, extending beyond the traditional passive management of bed rest and pain control alone. However, this study has several limitations. First, it was conducted at a single institution by a single investigator, which may limit the generalizability of the findings. Because the study was confined to one institution, its results may not be applicable to other settings or populations. This limitation affects the broader relevance of the conclusions, particularly in hospitals with differing patient demographics, technological resources, or levels of medical expertise. Despite its prospective design, the study’s small sample size and focus on a population from a single urban area further restrict the applicability of the findings. Studies conducted at single institutions often face the challenge of a limited sample size, which can reduce the statistical power of the results. Additionally, the lack of diversity in the patient population, such as a focus on individuals of smaller stature, may hinder the ability to extrapolate the results to broader populations, including those of average or larger stature or those with varying medical conditions. Moreover, the potential for residual confounding exists due to the study’s design. The small, heterogeneous study population may have limited the ability to achieve statistical significance. Another limitation is the absence of a robust control group or a comprehensive comparison framework, particularly if the study primarily evaluates the implementation of a new methodology without a thorough comparison to established practices outside the institutional context. This limitation makes it difficult to draw definitive conclusions regarding the superiority of the new methodology or to identify the specific conditions under which it is most effective. Generalizing the results to other clinical contexts remains challenging. Consequently, to validate these findings, multicenter, multinational, randomized controlled trials and prospective cohort studies are recommended, particularly in diverse patient populations and clinical settings. Ultimately, this research aims to provide foundational data for future multicenter studies to evaluate the clinical impact of LIPUS treatment in managing and progressing rib fractures resulting from thoracic trauma. Unfortunately, this study did not encompass a detailed evaluation of longer-term outcomes, such as accelerated fracture healing, callus formation, or a reduction in the incidence of nonunion.

Moreover, in South Korea, the majority of medical expenses for patient care and treatment are covered by a government-managed healthcare insurance system. However, certain innovative therapeutic modalities, such as LIPUS, are not currently reimbursed by public insurance. As a result, patients must bear the financial burden of these treatments. Although our study was conducted for research purposes and did not impose any financial burden on the participating patients, LIPUS is not yet covered by public healthcare insurance in South Korea. Consequently, in the current healthcare environment, a significant portion of the costs for such novel treatments would likely fall on individual patients. This raise concerns that the additional financial burden may hinder many patients from accessing LIPUS therapy, potentially limiting its widespread adoption despite its proven therapeutic benefits. This has led to discussions about the cost-benefit ratio of LIPUS, as its adoption and reimbursement policies vary widely depending on the healthcare systems and regulatory frameworks of different countries. Furthermore, placebo effects were observed in some patients, particularly in the control group, despite not receiving LIPUS therapy. This phenomenon may be attributed to patients perceiving LIPUS as a more proactive therapeutic intervention compared to traditional, passive approaches, such as absolute bed rest, commonly used to manage MRF. Although formal statistical analysis was not conducted, anecdotal evidence suggests that LIPUS may have contributed to earlier resolution in some cases of extrapleural hematoma presenting as a bruise. Furthermore, In the practical application of LIPUS for patients with MRFs, those with fractures in the posterior area may require positioning in lateral or prone positions to facilitate easy probe application. Despite careful adjustment of their positions, some patients have expressed difficulty or fear regarding these position changes, and there were also individuals who found the 15-minute LIPUS treatment duration in these positions uncomfortable.

Conclusions

The results of our study suggest that LIPUS treatments may significantly accelerate rib fracture healing and promote callus maturation in patients with MRFs resulting from severe thoracic injuries. Our analysis also indicates that LIPUS may enhance rib fracture healing while providing additional benefits, particularly in pain management. These findings are noteworthy, as LIPUS is an easily accessible ultrasonic device with minimal risk of complications. Its use not only has the potential to alleviate pain, shorten healing time, reduce disability, and provide substantial cost savings in cases of delayed union and nonunion fractures but also shows promise in the management of acute MRFs, an area that has been relatively underexplored. Moreover, rigorous clinical trials with high methodological quality are essential to clarify the optimal role of LIPUS in treating acute MRFs, as well as sternum fractures, which are among the most commonly observed injuries in thoracic trauma. Future research, supported by multidisciplinary collaboration and the integration of advanced techniques, should focus on patients at high risk of fracture healing complications, particularly those with acute rib fractures prone to nonunion. The most clinically significant benefit of LIPUS may lie in its ability to promote the early recovery of acute rib fractures, facilitating a quicker return to daily life and work, while substantially reducing the proportion of patients who progress to nonunion. If the therapeutic efficacy of LIPUS is confirmed to be consistent and reliable, it could provide significant benefits to a wide range of patients with thoracic injury.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the CONSORT reporting checklist. Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2024-2136/rc

Trial Protocol: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2024-2136/tp

Data Sharing Statement: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2024-2136/dss

Peer Review File: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2024-2136/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2024-2136/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the IRB of Konkuk University Chungju Hospital (IRB approval No. KUCH 2024-01-002). Prior to participation, all participants were provided with detailed information about the study’s objectives and procedures, and both verbal and written informed consent were obtained.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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