Evaluation of the Efficacy of Prolotherapy in Patients With Lateral Epicondylitis Using Shear-Wave Elastography

Introduction

Lateral epicondylitis is a common elbow injury characterized by symptoms such as decreased grip strength, restricted forearm rotation, and localized pain and tenderness over the lateral epicondyle [1]. This condition affects approximately 1% of the adult population worldwide and is most frequently observed between ages 35 and 55. Among athletes – particularly those who play tennis – the lifetime prevalence is notably higher, ranging between 40–50%, which is why it is commonly referred to as “tennis elbow” [2]. Initially defined as a “tendinitis,” lateral epicondylitis has since been re-evaluated through histopathological studies. Surgical pathology specimens from cases of primary lateral epicondylitis have shown no clear evidence of acute or chronic inflammation. These findings support current pathophysiological perspectives that characterize lateral epicondylitis as tendinosis resulting from repetitive microtrauma at the origins of the extensor carpi radialis brevis and extensor digitorum communis muscles [3,4]. Prolotherapy, first described by Dr. George Hackett, has since been widely used to treat various chronic musculoskeletal disorders [5,6]. The proposed mechanism of action involves the injection of proliferative agents into the target area, thereby triggering the release of local growth factors and inducing a controlled inflammatory response. This process initiates a reparative cascade involving inflammation, proliferation, and tissue remodeling, thereby stimulating natural tissue healing [7]. Prolotherapy is particularly favored in conditions associated with connective tissue degeneration and ligamentous laxity, as it supports functional recovery. In this method, a hypertonic dextrose solution is typically injected into soft tissues or joint spaces for regenerative purposes. Dextrose is commonly used due to its high compatibility with human biochemistry and favorable safety profile. Its low cost and widespread availability are additional advantages that contribute to its extensive clinical use [8].

Ultrasound elastography, widely used in the assessment of hepatic and breast tissues, has recently also gained increasing attention for musculoskeletal applications [9,10]. Recent studies have demonstrated its reliability in detecting changes in soft tissues under various physiological and pathological conditions. By providing novel and complementary information regarding tissue quality, ultrasound elastography adds an innovative dimension to conventional ultrasound imaging [11,12]. The technique is based on the principle that mechanical stress applied to a tissue produces variable levels of deformation depending on the underlying structural properties. Essentially, elastography comprises 2 primary techniques: strain elastography and shear-wave elastography (SWE). SWE was initially described by Sarvazyan and colleagues in 1998 [13]. Compared with magnetic resonance imaging (MRI), SWE offers several advantages, including lower operator dependence, greater accessibility, lower cost, and fewer contraindications [11,14–16].

SWE is initiated by delivering an acoustic radiation force impulse to the tissue of interest. This impulse induces tissue deformation, thereby propagating shear waves. The velocity of these shear waves is directly proportional to tissue stiffness and is typically measured in meters per second (m/s). These velocity values can be converted into elastic modulus values (Young’s modulus) using specific mathematical models [17]. To obtain accurate and consistent measurements, the ultrasound probe should be positioned parallel to the muscle fibers, and any external pressure on the tissue must be minimized during the examination. The diagnosis and evaluation of lateral epicondylitis are managed using subjective instruments such as the Oxford Elbow Score and the Patient-Rated Tennis Elbow Evaluation, which rely primarily on physical examination and activity level. These are pretty essential tests. In this context, our study employed SWE, which provides quantitative measurements of tendon stiffness and thickness. When this assessment is considered alongside subjective functional evaluations such as VAS, it is thought to provide a correlation between structural changes and functional improvements. Although functional elbow scores are accurate tools for evaluating treatment outcomes, they remain largely subjective; in contrast, SWE provides quantitative and objective data on the elastic properties of the examined tissue. This study aims to assess the effectiveness of prolotherapy in patients with lateral epicondylitis by evaluating changes in extensor tendon elasticity using SWE before and after treatment. The goal is to obtain quantitative, objective data to assess the therapeutic impact.

Material and Methods

The study received approval from the Clinical Research Ethics Committee of Malatya Turgut Özal University (approval number: 2025/111), and all participants provided written informed consent following a detailed explanation of the study procedures. Conducted between May and July 2025, the study included patients diagnosed with lateral epicondylitis by an orthopedic surgeon based on physical examination and clinical findings.

According to the power analysis, a sample size of 36 patients was deemed sufficient for this study. However, due to various reasons – including patients reporting improvement after the first session, non-compliance with the study schedule, or loss to follow-up – a total of 56 patients were initially enrolled to ensure the required number of participants was reached. Demographic and clinical information, including age, sex, dominant hand, and disease duration, was also collected. Exclusion criteria included a history of elbow fracture or surgery, systemic musculoskeletal disorders, and pregnancy.

Inclusion criteria for lateral epicondylitis diagnosis were as follows: a typical clinical history, tenderness over the lateral epicondyle, pain radiating from the lateral forearm toward the palm, which intensifies with wrist extension, and a positive Cozen’s test: With the forearm pronated and the elbow extended, resisting wrist dorsiflexion is performed. If tenderness and pain are present in the lateral epicondyle, the test is positive.

All participants underwent SWE of the affected elbow before and after local injection. A total of 3 sessions of local prolotherapy injections were administered – immediately after the initial assessment, at week 3, and at week 6. Patients presenting to the orthopedic outpatient clinic with elbow pain were randomly selected according to predefined inclusion and exclusion criteria. All participants received detailed information about the study and provided informed consent. Before the intervention, SWE was used to measure the elasticity and thickness of the CET. Subsequently, approximately 10 cc of 5% dextrose was injected into the CET origin region using a 22-gauge needle (Figure 1). The second SWE evaluation was performed 1 month after the final prolotherapy session (ie, at week 10). All ultrasonography and SWE examinations during the patients’ first and second visits were performed using the same ultrasound system (RS85 Prestige, Samsung Medison Co. Ltd.) equipped with a 12 MHz linear transducer. The same radiologists conducted all examinations to ensure consistency in image acquisition and measurement.

Patients were seated facing the examiner, with the elbow flexed to 90°, the forearm supinated, and the thumb pointing upward. The forearm remained relaxed during measurements, and the ultrasound probe was positioned perpendicular to the skin over the lateral epicondyle with minimal pressure. The end of the CET inserting on the lateral epicondyle of the humerus was imaged in a longitudinal plane, parallel to its fibers, to obtain standardized scans. Elastograms were displayed in dual mode, overlaid on the B-mode image. CET thickness was measured as the distance from the surface of the extensor tendon to the lateral epicondylar cortex.

SWE images were obtained using gray-scale imaging within a circular region of interest (ROI) with a diameter of approximately 0.2 cm. Attention was paid to avoid placing the circular ROI outside the boundaries of the CET or in areas close to the bone. CET stiffness was measured at least 5 times for each ROI, and the median value was used for analysis (Figure 2). All SWE measurements were expressed in kilopascals (kPa) and were accompanied by an automatically calculated reliability measurement index (RMI) to assess measurement consistency [15]. Based on previous studies, measurements with an RMI ≥0.8 and an interquartile range-to-median ratio (IQR/Med) ≤30% were considered reliable; therefore, these thresholds were adopted as quality criteria in this study. In a study evaluating tendon thickness and elasticity in supraspinatus tendinopathy using SWE, objective data on tendon thickness and elasticity were presented and correlated with functional shoulder scores [18].

Statistical analyses were conducted using NCSS 2020 (NCSS LLC, Kaysville, Utah, USA). Quantitative data were reported as mean±standard deviation, median, minimum, and maximum, while qualitative data were presented as frequencies and percentages. Data normality was assessed using the Shapiro-Wilk test and box plots. For normally distributed quantitative variables, t-test was used for independent group comparisons, and the Paired Sample t-test was applied for paired measurements. For non-normally distributed variables, independent groups were compared using the Mann-Whitney U test, and paired measurements were analyzed using the Wilcoxon Signed-Rank test. Correlations were assessed using Pearson’s or Spearman’s rank correlation, depending on the data distribution. Linear regression analysis was performed for further evaluation. Qualitative data were compared using Fisher’s exact test, and a P-value <0.05 was considered statistically significant with a 95% confidence interval.

Results

The study was conducted between May 8, 2025, and July 22, 2025, at Malatya Turgut Özal University Training and Research Hospital, with a total of 36 cases, of which 41.7% (n=15) were female and 58.3% (n=21) were male. The participants’ ages ranged from 25 to 61 years, with a mean age of 46.92±9.40 years (Table 1). Analysis of affected sides among participants revealed that 72.2% (n=26) of the patients experienced symptoms on the right side and 27.8% (n=10) experienced symptoms on the left (Figure 3).

Before-treatment and after-treatment values are referred to as kPa 1 and kPa 2. After treatment, there was a mean increase of 22.16±13.80 units. This difference in kPa 2 values compared with kPa 1 values was found to be statistically significant (P=0.001; P<0.01) (Table 2). For female patients, the increase was 21.85±16.37 units in kPa 2 values compared with kPa 1 values, and this increase was found to be statistically significant (P=0.048; P<0.05). For male patients, there was an increase of 22.38±12.06 units in kPa 2 values compared with kPa 1 values, and this increase was found to be statistically significant (P=0.005; P<0.01) (Table 2).

The Thickness 1 values for male patients were significantly higher than those for female patients (P=0.001; P<0.01). Similarly, the Thickness 2 values for male patients were also considerably higher compared with female patients (P=0.001; P<0.01) (Table 3).

In cases overall, there was an increase of 0.03±0.01 units in Thickness 2 values compared with Thickness 1 values, and this increase was found to be statistically significant (P=0.001; P<0.01) (Figure 4).

For female patients, there was an increase of 0.03±0.01 units in Thickness 2 values compared with Thickness 1 values, and this difference was found to be statistically significant (P=0.001; P<0.01). For male patients, there was an increase of 0.03±0.03 units in Thickness 2 values compared with Thickness 1 values, and this difference was also found to be statistically significant (P=0.001; P<0.01) (Table 3).

VAS1 and VAS2 values did not show a statistically significant difference between sexes (P>0.05) (Table 4). For all cases, a statistically significant decrease of 7.20±2.37 units was observed in VAS 2 values compared with VAS 1 values (P=0.001; P<0.01) (Figure 4).

For female patients, a statistically significant decrease of 7.54±2.20 units was observed in VAS 2 values compared with VAS 1 values (P=0.001; P<0.01). For male patients, a statistically significant decrease of 7.86±1.77 units was observed in VAS 2 values compared with VAS 1 values (P=0.001; P<0.01) (Figure 5).

Discussion

LIMITATIONS:

The absence of a control group represents the main limitation of our study; however, its originality lies in the statistical comparison of pre- and post-treatment measurements within the same patient cohort.

Conclusions

Prolotherapy, a treatment for lateral epicondylitis, resulted in significant clinical improvement in CET stiffness and marked pain reduction. SWE proved to be a reliable, objective, and non-invasive method for quantitatively assessing these changes before and after treatment. When examining the Thickness 1 and 2 measurements, male patients had significantly higher Thickness 1 and Thickness 2 values than female patients (P<0.01). Prolotherapy can be considered an effective therapeutic option for improving tendon structure and function in lateral epicondylitis. SWE, platelet-rich plasma, and dry needling can also be used to evaluate treatment methods other than prolotherapy for lateral epicondylitis. SWE may serve as a valuable tool for treatment monitoring and clinical decision-making.