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Background <p>Platelet-rich plasma (PRP) is widely used as an intra-articular treatment for knee osteoarthritis (KOA), but whether combining PRP with hyaluronic acid (HA), mesenchymal stem cells (MSCs), or ozone (O<sub>3</sub>) provides additional clinical benefit remains unclear. We conducted a systematic review and network meta-analysis (NMA) to compare the efficacy of PRP monotherapy with these three PRP-based combination strategies.</p> Methods <p>Twelve electronic databases were searched from inception to April 2026 for randomized controlled trials (RCTs) that compared intra-articular PRP alone with PRP combined with HA, MSCs, or O<sub>3</sub> in adults with KOA. Two reviewers independently performed study selection, data extraction, and risk of bias assessment using the Cochrane RoB 2 tool. The primary outcomes were changes in WOMAC total score and VAS pain score. A random-effects NMA was conducted within a frequentist framework in Stata 17.0. Treatment rankings were calculated using surface under the cumulative ranking curve (SUCRA) values.</p> Results <p>Eighteen RCTs involving 1,376 participants met the inclusion criteria. The evidence network was star-shaped, with PRP alone serving as the sole common comparator. For WOMAC function, PRP + HA was the only combination that demonstrated a statistically significant improvement over PRP alone (MD =  − 6.16, 95% CI − 9.71 to − 2.61, <i>P</i> &lt; 0.001). Differences were not significant for PRP + O<sub>3</sub> (MD =  − 9.65, 95% CI − 20.33 to 1.03) or PRP + MSC (MD =  − 0.80, 95% CI − 12.85 to 11.25). For VAS pain, PRP + HA again showed superior pain relief (MD =  − 1.01, 95% CI − 1.57 to − 0.44, <i>P</i> &lt; 0.001). PRP + MSC (MD =  − 0.77, 95% CI − 1.92 to 0.38) and PRP + O<sub>3</sub> (MD =  − 0.15, 95% CI − 1.87 to 1.57) did not differ significantly from PRP alone. SUCRA values ranked PRP + HA highest for VAS pain and second for WOMAC function. No significant publication bias was detected.</p> Conclusions <p>Among PRP-based combination therapies for KOA, the addition of HA to PRP is supported by the most consistent evidence for improving pain and function. Current data are insufficient to conclude that adding MSCs or O<sub>3</sub> provides any additional benefit. Standardized, large-scale RCTs with longer follow-up are needed to clarify the role of these emerging combinations.</p>

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Comparative efficacy of platelet-rich plasma monotherapy versus combination therapies for knee osteoarthritis: a systematic review and network meta-analysis

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年6月24日

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  • Dehao Luan,
  • Xiaonan Zhang,
  • Ziyi Zhang,
  • Xi Man,
  • Hai Bo

摘要

Background

Platelet-rich plasma (PRP) is widely used as an intra-articular treatment for knee osteoarthritis (KOA), but whether combining PRP with hyaluronic acid (HA), mesenchymal stem cells (MSCs), or ozone (O3) provides additional clinical benefit remains unclear. We conducted a systematic review and network meta-analysis (NMA) to compare the efficacy of PRP monotherapy with these three PRP-based combination strategies.

Methods

Twelve electronic databases were searched from inception to April 2026 for randomized controlled trials (RCTs) that compared intra-articular PRP alone with PRP combined with HA, MSCs, or O3 in adults with KOA. Two reviewers independently performed study selection, data extraction, and risk of bias assessment using the Cochrane RoB 2 tool. The primary outcomes were changes in WOMAC total score and VAS pain score. A random-effects NMA was conducted within a frequentist framework in Stata 17.0. Treatment rankings were calculated using surface under the cumulative ranking curve (SUCRA) values.

Results

Eighteen RCTs involving 1,376 participants met the inclusion criteria. The evidence network was star-shaped, with PRP alone serving as the sole common comparator. For WOMAC function, PRP + HA was the only combination that demonstrated a statistically significant improvement over PRP alone (MD =  − 6.16, 95% CI − 9.71 to − 2.61, P < 0.001). Differences were not significant for PRP + O3 (MD =  − 9.65, 95% CI − 20.33 to 1.03) or PRP + MSC (MD =  − 0.80, 95% CI − 12.85 to 11.25). For VAS pain, PRP + HA again showed superior pain relief (MD =  − 1.01, 95% CI − 1.57 to − 0.44, P < 0.001). PRP + MSC (MD =  − 0.77, 95% CI − 1.92 to 0.38) and PRP + O3 (MD =  − 0.15, 95% CI − 1.87 to 1.57) did not differ significantly from PRP alone. SUCRA values ranked PRP + HA highest for VAS pain and second for WOMAC function. No significant publication bias was detected.

Conclusions

Among PRP-based combination therapies for KOA, the addition of HA to PRP is supported by the most consistent evidence for improving pain and function. Current data are insufficient to conclude that adding MSCs or O3 provides any additional benefit. Standardized, large-scale RCTs with longer follow-up are needed to clarify the role of these emerging combinations.