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Clinical Efficacy of Platelet-Rich Plasma Injection and Its Association with Growth Factors in the Treatment of Mild to Moderate Knee Osteoarthritis: a Randomized Double-Blind Controlled Clinical Trial as Compared with Hyaluronic Acid

·Am J Sports Med·2021·110 citations·Hip & Knee
DOI·PubMed
SummaryAbstract on PubMed →

Single-center double-blind RCT (n=110, KL grade 1-3 knee OA) comparing one intra-articular injection of leukocyte-rich PRP versus hyaluronic acid. The primary endpoint was IKDC subjective score improvement at 6 months. Uniquely, 11 growth factors and cytokines were quantified in each patient's injected PRP to test whether biological composition predicts clinical response.

Study Snapshot

Design
Single-center double-blind RCT
Blinding: Double-blind
Setting: Single center, Samsung Medical Center, Seoul, Korea
Funding: Korean government (Ministry of Health and Welfare)
Objective
Whether intra-articular PRP injection is clinically superior to HA in KL grade 1-3 knee OA at 6 months
Outcome(s)
IKDC subjective score improvement from baseline at 6 months
Subjects
110 patients
  • 55PRP
  • 55HA
Inclusion
  • Age 40 years or older
  • Kellgren-Lawrence grade 1-3 knee OA
  • VAS pain greater than 40 mm at baseline
Exclusion
  • Hemoglobin less than 10 g/dL or platelets less than 100,000/mL
  • Autoimmune disease, active infection, or recent corticosteroid use
  • Pregnancy, immunosuppressant use, or enrollment in other trials
Follow-up
6 months (3 time points: 6 weeks, 3 months, 6 months)
Statistics
Student t testMann-Whitney U testPearson chi-square testKolmogorov-Smirnov normality test

Key Findings

  • PRP produced significantly greater IKDC improvement at 6 months (11.5 vs 6.3 points, P = .029). The PRP group exceeded the published MCID of 6.3 points. The HA group landed exactly at the MCID threshold — both treatments work, but PRP works more.
  • More PRP patients exceeded the VAS pain MCID at 6 months (P = .044). Mean PRP VAS improvement was 20.9 points, clearing the MCID of 19.9 points. HA improvement averaged only 13.6 points, falling below the threshold for clinically meaningful pain relief.
  • Patient Global Assessment favored PRP at 6 months (P = .035), but not at 6 weeks or 3 months. The benefit accrues over time. Early assessments will not capture the full advantage of PRP over HA.
  • Within the PRP group, PDGF-BB (P = .019) and PDGF-AB (P = .041) were the only factors significantly higher in patients who achieved the VAS pain MCID. Platelet count, leukocyte count, age, sex, BMI, and KL grade did not differ between responders and non-responders. The number on the platelet count label does not tell you who will respond.
  • WOMAC scores did not achieve MCID in either group at 6 months. Total WOMAC improvements were nearly identical (PRP 6.4 vs HA 6.5, P = .967). Only at 6 weeks did total WOMAC favor PRP (P = .013). WOMAC appears less sensitive than IKDC and VAS for detecting PRP benefit at this timeframe.
  • The GPS III system concentrated platelets approximately 3-fold (976,000 vs 234,000/mL) and leukocytes approximately 4.6-fold (29,400 vs 6,350/mL) over whole blood. These numbers define what leukocyte-rich PRP means quantitatively for this specific preparation system.
  • Adverse event rates were equivalent at 10.9% per group (P > .05), with no serious adverse events in either group. The safety profile of a single PRP injection is indistinguishable from HA.
Board PearlIn knee OA, PRP responders have higher PDGF-BB and PDGF-AB concentrations — platelet count alone does not predict who benefits.

Clinical Relevance

Most PRP trials report platelet counts and stop there — this trial directly addresses that gap by measuring 11 growth factors and cytokines in every patient's injected sample and correlating them with clinical response.

The clinical takeaway is two-part. First, PRP provides a real but modest advantage over HA at 6 months. The IKDC and VAS benefits are statistically significant and cross the MCID, but most secondary outcomes do not separate. Set patient expectations accordingly.

Second, when you counsel patients or evaluate commercial PRP systems, platelet count is the wrong metric. PDGF-BB and PDGF-AB concentrations distinguished responders from non-responders; platelet count, leukocyte count, and all other measured factors did not. Preparation method and kit selection matter because they determine growth factor yield, not just cell concentration.

This is a 6-month trial with a single injection and no placebo arm, so durability of benefit and the true placebo effect remain open questions.

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|

Clinical Efficacy of Platelet-Rich Plasma Injection and Its Association with Growth Factors in the Treatment of Mild to Moderate Knee Osteoarthritis: a Randomized Double-Blind Controlled Clinical Trial as Compared with Hyaluronic Acid

·Am J Sports Med·2021·110 citations·Hip & Knee
DOI·PubMed
SummaryAbstract on PubMed →

Single-center double-blind RCT (n=110, KL grade 1-3 knee OA) comparing one intra-articular injection of leukocyte-rich PRP versus hyaluronic acid. The primary endpoint was IKDC subjective score improvement at 6 months. Uniquely, 11 growth factors and cytokines were quantified in each patient's injected PRP to test whether biological composition predicts clinical response.

Study Snapshot

Design
Single-center double-blind RCT
Blinding: Double-blind
Setting: Single center, Samsung Medical Center, Seoul, Korea
Funding: Korean government (Ministry of Health and Welfare)
Objective
Whether intra-articular PRP injection is clinically superior to HA in KL grade 1-3 knee OA at 6 months
Outcome(s)
IKDC subjective score improvement from baseline at 6 months
Subjects
110 patients
  • 55PRP
  • 55HA
Inclusion
  • Age 40 years or older
  • Kellgren-Lawrence grade 1-3 knee OA
  • VAS pain greater than 40 mm at baseline
Exclusion
  • Hemoglobin less than 10 g/dL or platelets less than 100,000/mL
  • Autoimmune disease, active infection, or recent corticosteroid use
  • Pregnancy, immunosuppressant use, or enrollment in other trials
Follow-up
6 months (3 time points: 6 weeks, 3 months, 6 months)
Statistics
Student t testMann-Whitney U testPearson chi-square testKolmogorov-Smirnov normality test

Key Findings

  • PRP produced significantly greater IKDC improvement at 6 months (11.5 vs 6.3 points, P = .029). The PRP group exceeded the published MCID of 6.3 points. The HA group landed exactly at the MCID threshold — both treatments work, but PRP works more.
  • More PRP patients exceeded the VAS pain MCID at 6 months (P = .044). Mean PRP VAS improvement was 20.9 points, clearing the MCID of 19.9 points. HA improvement averaged only 13.6 points, falling below the threshold for clinically meaningful pain relief.
  • Patient Global Assessment favored PRP at 6 months (P = .035), but not at 6 weeks or 3 months. The benefit accrues over time. Early assessments will not capture the full advantage of PRP over HA.
  • Within the PRP group, PDGF-BB (P = .019) and PDGF-AB (P = .041) were the only factors significantly higher in patients who achieved the VAS pain MCID. Platelet count, leukocyte count, age, sex, BMI, and KL grade did not differ between responders and non-responders. The number on the platelet count label does not tell you who will respond.
  • WOMAC scores did not achieve MCID in either group at 6 months. Total WOMAC improvements were nearly identical (PRP 6.4 vs HA 6.5, P = .967). Only at 6 weeks did total WOMAC favor PRP (P = .013). WOMAC appears less sensitive than IKDC and VAS for detecting PRP benefit at this timeframe.
  • The GPS III system concentrated platelets approximately 3-fold (976,000 vs 234,000/mL) and leukocytes approximately 4.6-fold (29,400 vs 6,350/mL) over whole blood. These numbers define what leukocyte-rich PRP means quantitatively for this specific preparation system.
  • Adverse event rates were equivalent at 10.9% per group (P > .05), with no serious adverse events in either group. The safety profile of a single PRP injection is indistinguishable from HA.
Board PearlIn knee OA, PRP responders have higher PDGF-BB and PDGF-AB concentrations — platelet count alone does not predict who benefits.

Clinical Relevance

Most PRP trials report platelet counts and stop there — this trial directly addresses that gap by measuring 11 growth factors and cytokines in every patient's injected sample and correlating them with clinical response.

The clinical takeaway is two-part. First, PRP provides a real but modest advantage over HA at 6 months. The IKDC and VAS benefits are statistically significant and cross the MCID, but most secondary outcomes do not separate. Set patient expectations accordingly.

Second, when you counsel patients or evaluate commercial PRP systems, platelet count is the wrong metric. PDGF-BB and PDGF-AB concentrations distinguished responders from non-responders; platelet count, leukocyte count, and all other measured factors did not. Preparation method and kit selection matter because they determine growth factor yield, not just cell concentration.

This is a 6-month trial with a single injection and no placebo arm, so durability of benefit and the true placebo effect remain open questions.

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