To evaluate the combined effect of two different regenerative therapies, extracorporeal shock wave therapy (ESWT) and platelet-rich plasma (PRP), along with therapeutic exercise, in patients with lateral epicondylitis (LE). Prospective, Randomized, Sham-Controlled Trial. Outpatient clinic. Ninety one patients with LE for >3 months were randomly allocated into 3 groups. Participants were assigned to PRP+ESWT, Sham PRP +ESWT, or ESWT only treatment group. All groups received exercise therapy. The primary outcome was the VAS pain score. Secondary outcomes included handgrip strength, Patient-rated Tennis Elbow Evaluation (PRTEE), Quick Disabilities of the Arm, Shoulder, and Hand (Quick DASH), Short Form 36 (SF-36), ultrasonographic assessments (common extensor tendon [CET] measurement and total ultrasonography scale score [TUSS]), and isokinetic evaluation. Participants were evaluated three times: pre-treatment (T0), after 4 weeks (T1), and after 12 weeks (T2). The PRP group showed superiority over other groups in terms of VAS (activity and night) scores at follow-ups. With regard to the secondary outcomes, in the short term, the PRP group demonstrated a statistically significant difference in the PRTEE-function. In the 12th week, PRP outperformed only against ESWT in all PRTEE parameters, and also showed superior Quick DASH scores to the other groups. In handgrip strength, the PRP group demonstrated superiority over the Sham PRP group at T1 and over both groups at T2. In the isokinetic evaluation, PRP group showed superiority over the Sham PRP group in both wrist flexion/extension peak torque scores during follow-ups. No significant differences were found in any of the ultrasonographic parameters, including CET thickness and TUSS scores, between the groups at the 4th and 12th week. The combined application of ESWT and PRP in the management of LE has demonstrated superior efficacy, as evidenced by significant improvements in clinical parameters.
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