Objectives: Prolotherapy (PrT) involves the injection of a proliferant in order to irritate a microenvironment and promote healing via the inflammatory cascade. PrT has become an increasingly popular nonoperative treatment in orthopedics. However, numerous prolotherapy solutions exist and varying applications and results have been described. The purpose of this study is to review high-quality randomized controlled trials (RCTs) that analyzed efficacy and safety profiles of prolotherapy (PrT) treatments for the most common sports-related tendinopathies. Methods: All RCTs published in English between January 1st 1980 and July 30th 2021, reported in Embase, Medline, and Web of Science databases, were queried with search terms including sclerotherapy, prolotherapy, sports medicine, sports injuries, tendinopathies, and musculoskeletal pain/injuries. PRISMA guidelines were used. Studies analyzing tendinopathies using a RCT design were included, while case controls, reviews, and observational studies were excluded. Duplicates were eliminated through Endnote. The remaining articles were screened by titles, followed by abstract and then by full text analysis. The Cochrane collaboration tool was used to assess for risk of bias. Two researchers independently performed the screening and conflicts were resolved using Rayyan © software (Rayyan Systems Inc., Cambridge, MA, USA). Graphical representations were created using SPSS version 28.00. Results: Application of the inclusion and exclusion criteria yielded 20 RCTs (fig. 1): 6 studies on lateral epicondylitis (LE); 6 on rotator cuff tendinopathy (RC); 5 on plantar fasciitis (PF); 2 on Osgood-Schlatter disease (OSD); 1 on Achilles tendinosis. Most of the trials used dextrose injections over P2G or hypertonic glucose (fig. 2), and the most common studied conditions were LE and RC (fig.3). The average follow-up period was 12 weeks. No significant adverse effects were reported, and the most common outcome measures were visual analog scale (VAS), patient rated tennis elbow evaluation (PRTEE), quick- disabilities of the arm, shoulder, and hand (Q-DASH), and symptoms relief. For the treatment of LE, dextrose PrT was associated with significant improvement in VAS pain score at rest and PRTEE compared to normal saline (p<0.041, p<0.013 respectively). Additionally, compared to hyaluronic acid and lifestyle modifications, PrT showed significant improvement in VAS pain score with activity, Q-DASH, and PRTEE scores (p<0.04, p<0.04, p<0.05 respectively). For the treatment of RC, dextrose PrT was found superior to physiotherapy in the shoulder disability index (p<0.001). Finally, dextrose PrT demonstrated significant improvements in foot function index (p<0.001) for the treatment of PF, and reduction of symptoms in OSD (p<0.024) compared to physical therapy and lidocaine controls. Patients with AT had a more rapid improvement in symptoms in the combined PrT/eccentric loading exercises protocols compared to dextrose PrT alone (p<0.007). A graphical representation of the results is reported in figure 4. Conclusions: This systematic review summarized high quality RCTs and found PrT injections to be overall safe and effective in the treatment of sports-related tendinopathies. Further RCTs with larger sample sizes and comparisons to orthobiologics would add to the literature. Based on the current findings, sports medicine professionals may safely pursue PrT as an additional component of conservative treatment before surgery.
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