Iliotibial band syndrome (ITBS) is a frequent cause of lateral knee pain among physically active individuals and is typically managed with activity modification, non-steroidal anti-inflammatory drugs, and structured physiotherapy. Although most patients respond to conservative treatment, a subset remains symptomatic and may require alternative therapeutic strategies. Platelet-rich plasma (PRP) has gained attention as a biologic therapy for various tendinopathies; however, evidence regarding its efficacy in ITBS is limited.
PurposeTo evaluate the effectiveness of ultrasound-guided PRP injection compared with placebo in patients with refractory ITBS.
Study designProspective, randomized, double-blind, placebo-controlled clinical trial; Level I evidence.
MethodsSixty patients aged 18–50 years with clinically and radiologically confirmed ITBS refractory to at least 12 weeks of conservative treatment were randomly assigned in a 1:1 ratio to receive either leukocyte-poor PRP (n = 30) or placebo saline injection (n = 30). Injections were performed under ultrasound guidance at the distal iliotibial band near the lateral femoral epicondyle. Randomization was conducted using a computer-generated block sequence with concealed allocation. Patients and outcome assessors were blinded to treatment allocation. The primary outcome was change in Visual Analog Scale (VAS) pain score at 6 months. Secondary outcomes included the Lower Extremity Functional Scale (LEFS), return-to-sport rate, and patient satisfaction. Sample size was calculated based on a clinically meaningful difference of 2 points in VAS, with a power of 80% and α = 0.05, accounting for an estimated 20% dropout.
ResultsAt 6 months, the PRP group demonstrated a significantly greater reduction in VAS pain scores compared with the placebo group (mean difference 2.2 points; p < 0.001). Functional outcomes also improved significantly in the PRP group, with higher LEFS scores and a greater proportion of patients returning to sport. Patient satisfaction rates were higher in the PRP group. No serious adverse events were reported.
ConclusionUltrasound-guided leukocyte-poor PRP injection resulted in significantly greater pain reduction and functional improvement compared with placebo in patients with refractory ITBS. PRP may represent a promising minimally invasive treatment option for patients who fail conservative management.
Iliotibial band syndrome (ITBS) is one of the most common causes of lateral knee pain in physically active individuals, particularly runners and cyclists, accounting for approximately 5–12% of all running-related injuries.1 The condition typically arises from repetitive compression of the distal iliotibial band (ITB) over the lateral femoral epicondyle during knee flexion and extension, leading to localized inflammation, irritation of underlying tissues, and activity-related pain.2 More recent evidence suggests that ITBS may primarily represent a compressive syndrome involving the highly innervated fat and connective tissues located between the ITB and the lateral femoral epicondyle, rather than simple friction alone.3,4
The ITB is a thick longitudinal fibrous structure extending from the tensor fascia lata and gluteus maximus proximally to its distal insertion at the Gerdy tubercle on the anterolateral tibia. During knee motion, the distal ITB passes over the lateral femoral epicondyle, particularly around 30° of flexion, which has been traditionally implicated in symptom development.3,5 Clinically, patients with ITBS present with lateral knee pain exacerbated by running, cycling, or repetitive knee flexion activities. Examination often reveals localized tenderness over the lateral femoral epicondyle, a positive Noble compression test, and tightness of the ITB demonstrated by the Ober test.6 Ultrasound findings include soft-tissue edematous swelling or discrete fluid collection, suggestive of bursitis, between the iliotibial band and the lateral femoral epicondyle.7 Magnetic resonance imaging (MRI) may reveal thickening of the distal ITB, increased signal intensity in surrounding soft tissues, or fluid accumulation deep to the band, supporting the diagnosis and excluding other causes of lateral knee pain.8–10
Conservative management—including activity modification, nonsteroidal anti-inflammatory drugs (NSAIDs), stretching, and structured physiotherapy focusing on hip abductor strengthening and biomechanical correction—remains the first-line treatment and is effective in most patients.8,11 Nevertheless, approximately 10–15% of patients continue to experience persistent symptoms despite appropriate nonoperative management.12 In refractory cases, interventions such as corticosteroid injections, extracorporeal shockwave therapy, or surgical release of the distal ITB may be considered, though outcomes are variable and not without potential complications.13,14
Platelet-rich plasma (PRP) has emerged as a biologic treatment for various musculoskeletal disorders, particularly tendinopathies. PRP is an autologous blood product containing a concentrated number of platelets and growth factors—including platelet-derived growth factor (PDGF), transforming growth factor-β (TGF-β), vascular endothelial growth factor (VEGF), and insulin-like growth factor-1 (IGF-1)—which may enhance tissue healing, stimulate collagen synthesis, and modulate inflammation. Several randomized controlled trials have reported encouraging, though mixed, results with PRP in lateral epicondylitis, patellar tendinopathy, long head of biceps tendinopathy, planter fasciitis and Achilles tendinopathy.14–20
Despite growing interest in PRP therapy, no clinical trial has specifically investigated its role in ITBS. Existing reviews and case-based reports discuss corticosteroid injections and theoretically mention PRP, but empirical evidence is lacking.21,22 Therefore, the present study represents the first prospective, randomized, placebo-controlled trial evaluating ultrasound-guided PRP injection in patients with refractory ITBS. The aim was to determine whether PRP provides greater pain relief and functional improvement compared with placebo, addressing an important gap in the literature.
MethodsStudy design and ethical considerationsThis study was designed as a prospective, randomized, double-blind, placebo-controlled clinical trial to evaluate the efficacy of PRP injection in patients with refractory ITBS. The study protocol was reviewed and approved by the institutional ethics committee prior to patient recruitment (IRB No. MIH‑2023‑PRP‑ITBS), and all procedures were conducted in accordance with the ethical principles outlined in the Declaration of Helsinki and subsequent amendments.23 All participants provided written informed consent after receiving a detailed explanation of the study procedures, potential benefits, and possible risks.
Patient selectionPatients presenting with persistent lateral knee pain suggestive of ITBS were screened between January 2023 and March 2024 at a tertiary sports medicine center. The diagnosis of ITBS was established based on clinical examination and imaging findings consistent with previous diagnostic criteria.22,24,25
Inclusion criteria were:
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Age between 18 and 50 years.
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Clinical diagnosis of ITBS characterized by lateral knee pain aggravated by repetitive knee flexion activities.
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Positive Noble compression test or Ober test.
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Symptoms persisting for at least 3 months.
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Failure of structured conservative treatment including NSAIDs, activity modification, and supervised physiotherapy.
Exclusion criteria included:
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Previous surgery involving the affected knee.
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Systemic inflammatory or rheumatologic disease.
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Coagulopathy or platelet disorders.
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Corticosteroid injection within the previous 3 months.
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Active infection around the knee.
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Pregnancy.
Magnetic resonance imaging (MRI) was performed when necessary to confirm distal ITB inflammation and exclude alternative causes of lateral knee pain such as lateral meniscus pathology or osteochondral lesions.10,25
Randomization and blindingParticipants meeting the eligibility criteria were randomly assigned in a 1:1 ratio to either the PRP group or the placebo group. Randomization was performed using a computer-generated block randomization sequence with variable block sizes to ensure balanced allocation. The sequence was generated by an independent statistician not involved in patient recruitment or outcome assessment.
Allocation concealment was maintained using sequentially numbered sealed opaque envelopes opened at the time of injection. The study employed a double-blind design, in which both patients and outcome assessors were unaware of treatment allocation. The injecting physician was not involved in postoperative follow-up or data analysis to preserve blinding integrity.
Preparation of platelet-rich plasmaAutologous PRP was prepared using a standardized double-spin centrifugation protocol. Approximately 30 mL of peripheral venous blood was collected from each participant assigned to the PRP group using the RegenKit-BCT® system (Regen Lab SA, Le Mont-sur-Lausanne, Switzerland) according to the manufacturer’s instructions.The first centrifugation step separated plasma from erythrocytes, followed by a second centrifugation to concentrate platelets. This process yielded leukocyte-poor PRP with an approximate platelet concentration of 4–5 times the baseline levels, consistent with previously described preparation techniques used in musculoskeletal applications.26–29 Although exact baseline platelet counts and absolute platelet doses were not routinely measured, the same preparation kit and standardized processing protocol were used across all patients to ensure consistency of the injected PRP product and reproducibility of the intervention.
The final PRP volume obtained for injection was 3 mL. For the placebo group, 3 mL of sterile normal saline was prepared in an identical syringe to maintain blinding.
Injection techniqueAll injections were performed under ultrasound guidance by a single orthopedic surgeon experienced in musculoskeletal interventions to ensure procedural consistency. The patient was positioned in the supine position with the knee slightly flexed. After sterile skin preparation and local anesthesia of the skin with lidocaine, a high-frequency linear ultrasound probe (7–12 MHz, Mindray Medical International Limited, Shenzhen, China) was used to identify the distal iliotibial band at the level of the lateral femoral epicondyle, which represents the most common site of symptomatic irritation in ITBS.7
A 22-gauge needle was introduced using an in-plane technique, and either 3 mL of PRP or 3 mL of saline was injected into the area deep to the distal iliotibial band adjacent to the lateral femoral epicondyle. Care was taken to distribute the injectate along the inflamed region of the band and surrounding soft tissues (Fig. 1).
Post-injection rehabilitation protocol
Following the injection, patients were advised to limit strenuous physical activity for 48 h. Thereafter, all participants followed a standardized rehabilitation protocol supervised by a single experienced sports physiotherapist at the same rehabilitation center to ensure consistency and protocol adherence across all participants. The rehabilitation programs consisting of progressive stretching of the iliotibial band and strengthening of the hip abductor musculature, which are considered key components in the treatment of ITBS.30,31
Gradual return to running or sports activity was permitted after 4–6 weeks depending on symptom improvement. Return to the previous level of sport was defined as the ability to resume pre-injury sports activity at the same intensity and frequency without pain or functional limitation, as confirmed by both patient self-report and clinical evaluations.
Medical clearance for return to sport was determined by the treating orthopedic surgeon based on the absence of lateral knee pain, full range of motion, no tenderness over the iliotibial band, and the ability to perform sport-specific functional activities without symptoms.
Outcome measuresThe primary outcome measure was the change in Visual Analog Scale (VAS) pain score from baseline to 6 months. The VAS is a validated and widely used tool for assessing pain intensity in musculoskeletal conditions.32
Secondary outcome measures included:
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Lower Extremity Functional Scale (LEFS) score.
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Rate of return to pre-injury sports activity.
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Patient satisfaction, measured using a 5-point Likert scale.
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Occurrence of treatment-related complications.
Clinical assessments were performed at baseline, 6 weeks, 3 months, and 6 months after the injection.
Sample size calculationSample size calculation was performed using G Power software (version 3.1, Heinrich Heine University, Düsseldorf, Germany). The calculation was based on detecting a minimum clinically important difference of 2 points in the Visual Analog Scale (VAS) score between the two groups, assuming a standard deviation of 2 points, a two-sided alpha level of 0.05, and a statistical power of 80%. The minimum required sample size was estimated to be 16 patients per group. To account for potential dropouts and to enhance the statistical robustness of the analysis, 30 patients were ultimately included in each group, resulting in a total sample size of 60 participants.
Data analysis was performed using SPSS statistical software. Continuous variables were expressed as mean ± standard deviation, whereas categorical variables were reported as frequencies and percentages. Between-group comparisons were performed using the independent samples t-test for continuous variables and the chi-square test for categorical variables. Repeated measures analysis of variance was used to evaluate changes in outcome scores over time.
A p-value < 0.05 was considered statistically significant.
Statistical analysis was performed according to the intention-to-treat principle.
ResultsPatient enrollment and follow-upA total of 84 patients presenting with lateral knee pain suggestive of iliotibial band syndrome were screened for eligibility. After applying the inclusion and exclusion criteria, 60 patients with refractory ITBS were enrolled and randomized into two groups: PRP group (n = 30) and placebo group (n = 30). During follow-up, three patients in the placebo group and two patients in the PRP group were lost to follow-up, one patient in each group discontinued resulting in 53 patients completing the 6-month evaluation (Fig. 2).
The overall follow-up rate was 91.7%, which was considered acceptable for the final analysis. All analyses were performed according to the intention-to-treat principle, with missing data managed using last observation carried forward where appropriate.
Baseline characteristicsThe two groups were comparable with respect to demographic and clinical variables at baseline. There were no statistically significant differences between the groups in terms of age, sex distribution, body mass index (BMI), duration of symptoms, baseline VAS pain scores, or baseline LEFS scores (p > 0.05).
The mean age of the participants was 32.6 ± 7.8 years in the PRP group and 33.1 ± 8.1 years in the placebo group. The mean duration of symptoms prior to enrollment was 6.8 ± 2.4 months in the PRP group and 6.5 ± 2.7 months in the placebo group (Table 1).
Baseline demographic and clinical characteristics of the study population.
Values presented as mean ± SD or frequency (%).
Both groups demonstrated improvement in pain scores over the course of follow-up; however, the magnitude of improvement was significantly greater in the PRP group (Fig. 3).
At baseline, the mean VAS pain score was 7.3 ± 1.1 in the PRP group and 7.1 ± 1.2 in the placebo group (p = 0.47). At the 6-month follow-up, the mean VAS score decreased to 1.8 ± 1.2 in the PRP group compared with 4.8 ± 1.6 in the placebo group (Table 2).
Clinical outcomes of PRP versus placebo injection in refractory ITBS over time.
ITBS = Iliotibial band syndrome.
VAS = Visual Analog Scale.
LEFS = Lower Extremity Functional Scale.
The mean reduction in VAS score from baseline to 6 months was 4.7 points in the PRP group versus 2.5 points in the placebo group, representing a statistically significant difference between groups (p < 0.001).
Secondary outcome: functional improvementFunctional outcomes measured using the Lower Extremity Functional Scale (LEFS) also showed greater improvement in the PRP group (Fig. 4).
The baseline LEFS score was 48.6 ± 7.9 in the PRP group and 49.2 ± 8.1 in the placebo group (p = 0.72). At the 6-month follow-up, the mean LEFS score improved to 73.2 ± 6.9 in the PRP group compared with 59.8 ± 9.0 in the placebo group. The difference between the groups was statistically significant (p = 0.002) (Table 2).
Return to sports activityReturn to the previous level of sports or running activity was observed in 25 patients (83.3%) in the PRP group compared with 17 patients (56.7%) in the placebo group at the 6-month follow-up. This difference was statistically significant (p = 0.03) (Fig. 5).
Patient satisfaction
Patient satisfaction scores favored the PRP group. At the final follow-up, 80% of patients in the PRP group reported being satisfied or very satisfied with the treatment, compared with 53% in the placebo group (Table 3).
Final clinical outcomes, return to pre injury sports, and patient satisfaction at 6 months post PRP versus placebo injection in refractory ITBS.
ITBS = Iliotibial band syndrome.
LEFS:lower extremity function scale.
No major complications such as infection, neurovascular injury, or thrombotic events were observed in either group. Mild post-injection discomfort at the injection site was reported by five patients in the PRP group and three patients in the placebo group, which resolved spontaneously within several days (Table 4).
Adverse events of PRP versus placebo injection in refractory ITBS over time.
ITBS = Iliotibial band syndrome.
To the best of our knowledge, this study represents the first prospective, randomized, double-blind, placebo-controlled trial evaluating the efficacy of ultrasound-guided platelet-rich plasma (PRP) injection in patients with refractory iliotibial band syndrome (ITBS). The findings of the present study suggest that PRP may provide clinically meaningful benefits in the management of refractory ITBS.
The principal finding of the present study is that a single ultrasound-guided leukocyte-poor PRP injection resulted in significantly greater pain reduction, improved functional outcomes, and higher return-to-sport rates compared with placebo at 6 months of follow-up (Fig. 6).
Responder rate defined as the proportion of patients achieving at least 50% reduction in Visual Analog Scale (VAS) pain score at 6 months. Data are presented as mean percentages with standard error bars. The PRP group demonstrated a significantly higher responder rate compared with the placebo group (p < 0.001).
ITBS remains one of the most common overuse injuries among athletes particularly runners and cyclists, and although conservative management is effective in the majority of patients, a subset continues to experience persistent symptoms despite adequate rehabilitation programs.33–35 For these patients, treatment options remain limited and include corticosteroid injections, extracorporeal shockwave therapy, or surgical intervention, different options for management of ITBS were summarized in (Table 5). However, these treatments may be associated with variable outcomes or potential adverse effects.36–40
Representative examples of conservative, injection-based, and surgical treatment strategies reported for iliotibial band syndrome in the literatures.
Corticosteroid injections have traditionally been used in the management of refractory ITBS due to their potent anti-inflammatory properties and ability to provide rapid symptom relief. However, their effects are frequently transient, and concerns have been raised regarding potential adverse effects, including tendon weakening, recurrence of symptoms, and possible tissue degeneration with repeated use. In contrast, biologic therapies such as PRP have gained increasing attention in sports medicine because of their potential to enhance tissue healing and modulate inflammation. PRP contains a high concentration of platelets and growth factors, including platelet-derived growth factor, transforming growth factor-β, and vascular endothelial growth factor, which may stimulate fibroblast proliferation, collagen synthesis, and angiogenesis in injured soft tissues.19,20,40
The findings of this trial are consistent with previously reported results of PRP in other chronic tendinopathies, including lateral epicondylitis, patellar tendinopathy, long head of biceps tendinitis, and Achilles tendinopathy, where PRP has demonstrated variable but generally favorable outcomes in terms of pain reduction and functional recovery14,16,18–20 Nevertheless, the heterogeneity in PRP preparation methods, platelet concentrations, injection techniques, and patient selection across studies has contributed to inconsistent results in the literature. These factors underscore the importance of standardized protocols when evaluating biologic therapies.41–44
An important observation in the current study is that the placebo group also demonstrated a clinically meaningful improvement in pain and functional outcomes over time. This finding is not unexpected and may be attributed to several factors, including the natural history of ITBS, the effect of a structured and supervised rehabilitation program, and the well-recognized placebo effect associated with injection-based interventions. These results highlight the necessity of placebo-controlled designs in accurately determining the true efficacy of emerging biologic treatments.
The superior outcomes observed in the PRP group suggest that PRP may provide an additive benefit beyond rehabilitation alone. The biologic rationale for PRP use is supported by its high concentration of growth factors, such as platelet-derived growth factor, transforming growth factor-β, and vascular endothelial growth factor, which are known to stimulate fibroblast proliferation, collagen synthesis, and angiogenesis. In the context of ITBS, which is increasingly understood as a compressive and inflammatory condition involving highly innervated peritendinous tissues, these effects may contribute to improved tissue remodeling and symptom resolution.
The use of a single PRP injection in this study was intentional to ensure standardization of the intervention and reduce variability in treatment exposure. While some authors advocate for multiple PRP injections, current evidence remains inconclusive regarding the optimal number and frequency of injections. Therefore, the present study provides valuable insight into the efficacy of a single-injection protocol, which may have practical advantages in terms of cost, patient compliance, and clinical feasibility. Another important strength of the current study is the use of ultrasound guidance during the injection procedure, which allowed precise localization of the distal iliotibial band and accurate delivery of the injectate to the affected region. Previous studies have demonstrated that ultrasound guidance improves the accuracy of musculoskeletal injections and may enhance clinical outcomes.7,14
Despite these promising findings, several limitations should be acknowledged. First, although the sample size was adequate to detect statistically significant differences in the primary outcome, larger multicenter trials would enhance the generalizability of the results. Second, the follow-up duration was limited to 6 months, and therefore, the long-term durability of PRP treatment remains uncertain. Third, structural changes within the iliotibial band were not evaluated using follow-up imaging modalities such as ultrasound or MRI.
Additionally, detailed characterization of PRP composition, including baseline platelet counts and absolute platelet dose, was not available, which may limit comparability with other studies and represents an area for improvement in future research. Furthermore, although the study was prospectively designed and randomized, it was not registered in a public clinical trials registry, which constitutes a methodological limitation.
Future studies should aim to establish standardized PRP preparation protocols, determine the optimal injection regimen, and evaluate long-term outcomes. Comparative studies between PRP and other commonly used interventions, such as corticosteroid injections or shockwave therapy, would also be valuable in defining the role of PRP within the treatment algorithm of ITBS.
In conclusion, ultrasound-guided leukocyte-poor PRP injection appears to be a safe and effective treatment option for patients with refractory iliotibial band syndrome. It provides significant pain reduction, functional improvement, and higher return-to-sport rates compared with placebo. These findings support the growing role of biologic therapies in the management of chronic overuse musculoskeletal condition.
DeclarationsConsent for publicationWritten informed consent was obtained from all participants.
FundingThere is no funding source.
Availability of data and materialThe datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
CRediT authorship contribution statementAshraf Mohamed Attiah Elazab: Conceptualization, Methodology, Investigation, Data curation, Formal analysis, Supervision, Writing – original draft, Writing – review & editing. Asmaa Salama Nasser: Investigation, Data curation, Validation, Writing – review & editing. Ahmed Sabry Mahmoud: Data curation, Formal analysis, Resources, Writing – review & editing.
The authors declare that he have no competing interests.
Not applicable.
