Table 3. Platelet-rich-plasma (PRP): Key studies showing limited or inconclusive evidence of PRP’s effectiveness in knee osteoarthritis (KOA).

This table presents an overview of studies that have investigated PRP’s efficacy in treating KOA and have reported limited or inconclusive evidence. The studies highlighted in the table have either found PRP to be effective in reducing symptoms compared to baseline (for a shorter duration) or have found no statistically significant superiority of PRP over other non-surgical treatments currently in use, emerging non-surgical treatments, or a placebo. However, some of these conclusions have lost their significance, or the trials have lost their ability to be adequately compared to the rest due to the lack of a placebo, statistical analysis, or occasional improper statistical analysis. In some instances, PRP has only been effective in improving pain or function for a single time frame. Furthermore, some clinical trials, such as the one conducted by Tucker et al. (2021) [28], may not be able to attribute the effect, or lack thereof, of PRP on patients' VAS and WOMAC scores due to a relatively smaller sample size, despite being interesting for their deep dive into the changes of the synovial environment. 

Note: All studies included are clinical trials that met the inclusion criteria for this review and carry a clinical evidence level of II or higher. 

ACS, Autologous Conditioned Serum; AS, Visual Analogue Scale; EQ-5D-5L, EuroQol Five-Dimension Five-Level Index; HA, Hyaluronic Acid; KOOS, Knee Injury and Osteoarthritis Outcome Score; mL, Milliliters; MRI, Magnetic Resonance Imaging; p, Probability; PRL, Prolotherapy; SF, Synovial Fluid; vs., Versus; WOMAC, Western Ontario and McMaster Universities Osteoarthritis Index.

Authors	Sample Size	Age (Year)	Dose/Platelet Concentration	PRP Type	Treatment Groups	Assessment Time	Assessment Tools	Findings
Bennell et al. (2021) [24]	288 patients	50 or older	5 mL dose weekly for 3 weeks at 1.6-5x the whole blood	Non-activated and leukocyte-poor	Placebo vs. PRP (144 each)	Baseline and 12 months	Pain scale 1-11 and the MRI for imaging of medial tibial cartilage volume	Intergroup analysis showed no significant difference in pain (p = 0.17) and cartilage volume (p = 0.81) between the two groups. The patients in the PRP group reported lower pain scores than baseline (no statistical comparison was available). The placebo group had a more minor loss of cartilage.
Dório et al. (2021) [25]	62 patients	45-80	1.4-5 mL dose biweekly for 2 weeks at ~3x the whole blood (standardized to 1 million platelets/cubic millimeters)	Non-activated and leukocyte-poor	PRP (20) vs. Plasma (21) vs. Saline (21)	Baseline, 6 weeks, and 12 weeks	VAS, WOMAC, and KOOS	A significant decrease was observed from baseline on VAS in all three groups. Intergroup analysis revealed that only one section of the KOOS scale, sport/recreation 0-100, demonstrated a significant decrease in the PRP group compared to the plasma and saline groups (p = 0.005).
Küçükakkaş et al. (2022) [26]	40 patients	18-80	Single injection at 7.66x the whole blood	Non-activated and leukocyte-poor	PRP (20) vs. HA (20)	Baseline, 1 month, and 6 months	VAS-rest, VAS-movement, WOMAC, Femoral Cartilage (medial and lateral) thickness	The patients in both the PRP and HA groups experienced a significant improvement in pain reduction (p < 0.05) and functional improvement (p < 0.05) compared to baseline. However, there was no significant difference between PRP and HA group. HA group showed increase in femoral cartilage thickness in the medial, lateral, and mean cartilage (p = 0.003, p < 0.001, p < 0.001, respectively). In contrast, the PRP group had no significant increase in cartilage thickness.
Pishgahi et al. (2020) [27]	92 patients	No age restriction	Dose weekly for 2 weeks at 4x the whole blood	Non-activated and leukocyte-poor	PRP (30) vs. PRL (30) vs. ACS (34)	Baseline, 1 month, and 6 months	VAS and WOMAC	The PRP group had a significant reduction in VAS scores only at the 1-month time frame (p = 0.019) when compared to the baseline. The ACS group had a significant decrease in VAS scores for both time frames, with p = 0.011 at one-month follow-up and p < 0.001 at six-month follow-up. The PRL group did not experience pain reduction throughout the study. The PRP and ACS groups showed no significant changes in WOMAC scores at the 1-month time frame.   However, there was significant reduction in WOMAC scores in both PRP and ACS group at six-month follow-up (p = 0.037 and p < 0.001, respectively).
Tucker et al. (2021) [28]	16 patients	40 or older	Single 5mL injection at 2.59x the whole blood	Non-activated and leukocyte-poor	PRP (10) vs. Saline (6)	Baseline, 3 months, 6 months, and 12 months (radiographic assessment at 6 months)	VAS, WOMAC, SF analysis, and radiograph	The PRP group showed a significant reduction in stiffness after three (p < 0.05), six (p < 0.05), and 12 months (p < 0.05), and also experienced a reduction in physical function impediments after three (p < 0.05) and six months (p < 0.05). The VAS scores consistently showed a decrease in pain for the PRP group; however, the reduction was not statistically significant. A significant rise in the alpha-2-macroglobulin protein (p < 0.005) was noted in the SF of the group treated with PRP. Due to the limited sample size, the radiographic assessment did not provide adequate information to draw significant conclusions.
Lewis et al. (2022) [29]	102 patients	18 or older	Saline + PRP: single injection at 2x the whole blood PRP only: Dose weekly for 3 weeks at 2x the whole blood	Non-activated and leukocyte-poor	Saline (28) vs. Saline + PRP (47) vs. PRP (27)	Baseline, 6 weeks, 12 weeks, 26 weeks, and 52 weeks	KOOS and EQ-5D-5L	Both the saline and single-dose PRP groups showed decreased scores at all the follow-up time points (p < 0.0041). The full-dose PRP group only achieved statistical significance in the final measurement at 52 weeks (p = 0.007). The intergroup analysis only revealed a substantial decrease in scores at a single time frame, 12 weeks, and only within the full-dose PRP group.   For the intragroup analysis of the EQ-5D-5L test, the saline group showed a significant decrease in scores at the 12-week measurement (p = 0.036). The single-dose PRP group recorded a significant decline in scores at the 6, 12, and 26-week measurements (p = 0.036), while the full-dose PRP group had no significant effect on scores throughout the study.   Intergroup analysis of the EQ-5D-5L showed insignificant differences between both PRP groups and the saline control group throughout the study.