In a recent publication, Hohmann (2024) suggested that a high platelet dose would be an effective treatment for osteoarthritis25. Hohmann proposed that a dose of fewer than 2.5 billion platelets is ineffective25, while a dose of more than 5 billion platelets yields good results both 6 and 12 months post-treatment. However, the publication also mentioned that questions remain about whether PRP needs activation, the optimal dose, injection frequency, platelet separation methods, etc., which are still unclear25. Hohmann's suggestion is consistent with the results of an earlier study conducted by Patel et al. (2024). In a triple-blind clinical study, Patel et al. (2024) compared the treatment efficacy of a 2.82 billion platelets dose against a 5.65 billion platelets dose for knee osteoarthritis. Although patients from both groups showed improvement in scores compared to before treatment, a better outcome was recorded in the group receiving a higher platelet dose (p < 0.001). Patient satisfaction with treatment results after 6 months also showed a significant difference, with 96% of patients treated with the higher dose satisfied compared to 68% of patients treated with the lower platelet dose26.

These results were confirmed by a recent study27. Berrigan et al. (2024) analyzed 29 studies and showed that the studies concluding beneficial effects of PRP injections used an average platelet dose of over 5 billion platelets (5.464 ± 511), whereas the studies reporting no statistical difference used a platelet dose of only 2 billion platelets (2.253 ± 753)27. Indeed, the study by Bennell et al. (2021) was among those who did not support the use of PRP in the treatment of knee osteoarthritis28. In this study, the research group was injected with LP-PRP three times consecutively over three weeks compared to the control group (saline injection). The results showed no differences in symptoms or joint structures after 12 months28. The reason for this non-responsiveness to treatment in this study might be the platelet dose. According to the data provided by the authors, the platelet dose used was relatively low, averaging 1.6 billion platelets in 5 mL PRP28.

In particular, in the study by Bansal et al. (2021) conducted on patients with Grade III knee osteoarthritis (over 80% of patients with Grade III knee osteoarthritis), the research group used a very high platelet dose (10 billion platelets in 8 mL injection)29. The results showed that in patients with Grade III knee osteoarthritis, PRP injections were also effective, with a significant reduction in WOMAC score, an increase in IKDC score, and an increase in 6-min pain-free walking distance after 1 year. This study also affirmed that the effectiveness of treatment does not depend on the number of platelet enrichment processes or platelet density but solely on the total number of platelets29.

The treatment efficacy of PRP depends not only on the number of platelets within the preparation but also on the type of PRP. Currently, based on the presence of leukocytes within PRP preparations, scientists classify PRP into three main types: Pure PRP, Leukocyte-Poor PRP (LP-PRP), and Leukocyte-Rich PRP (LR-PRP). According to Xiong et al. (2023), a meta-analysis of 24 Randomized Controlled Trials (RCTs) showed that the treatment efficacy of LP-PRP was better than that of LR-PRP in the treatment of osteoarthritis30. However, another analysis by Kim et al. (2023) showed that both LP-PRP and LR-PRP resulted in improved joint pain compared to Hyaluronic Acid (HA) injections31. However, in this analysis, Kim et al. reported no difference in pain and swelling between LP-PRP and HA injections, but LR-PRP injections caused pain and swelling related to the injection procedure (with an odds ratio of 3.3). This observation was analyzed by Kim et al. (2023) in 21 level 1 RCTs involving 1077 PRP joint injections and 1009 HA joint injections. A previous publication by Kim et al. (2021) also stated that LR-PRP injections cause more pain and swelling than LP-PRP injections32. Chen et al. (2023) also found LP-PRP to be better than LR-PRP in changing the IKDC scores in treating knee osteoarthritis33. However, another pooled analysis by Abbas et al. (2023) suggested no significant difference in the treatment of knee osteoarthritis between LP-PRP and LR-PRP34.

Figure 1

The activation of PRP before injection also affects treatment efficacy for knee osteoarthritis. To clarify this, Simental-Mendia et al. (2022) performed a meta-analysis of clinical studies divided into two groups: those using activated PRP and those using non-activated PRP. The authors summarized 14 RCTs with a total of 1292 patients in both groups: the group using activated PRP and the group using non-activated PRP. The results showed that exogenous (pre-activation) activated PRP is more effective in improving pain and functional scores in treating knee osteoarthritis35.

Tao et al. (2023) analyzed 7 studies with 575 patients to compare the efficacy of injecting 1 dose, 2 doses, and 3 doses of PRP. The results showed that injecting three doses of PRP significantly improved the VAS score after 12 months (p < 0.0001), whereas injecting two doses and one dose resulted in similar outcomes after 12 months of injection36. Recently, Zhuang et al. (2024) compared the response to 1, 3, and 5 doses of PRP in the treatment of knee osteoarthritis in 106 patients. The research group showed that injecting three or five doses of PRP is safe and more effective than a single injection in improving joint pain, joint function, and motor function in patients with Grade I-III knee osteoarthritis. However, the study showed no significant difference between three and five injections. Therefore, the research group suggested that three injections are necessary to achieve optimal efficacy in treating knee osteoarthritis37.

In 2023, Saraf et al. conducted a randomized controlled clinical trial to evaluate the effectiveness of three consecutive PRP injections (one injection each month) in treating Grade II and III knee osteoarthritis (Kellgren-Lawrence scale)38, 39. In this study, 31 patients received three PRP injections and 27 received saline injections. The results confirmed that at 3, 6, and 12 months, 3 consecutive PRP injections significantly improved VAS, WOMAC in patients with Grade II and III knee osteoarthritis compared to the saline injection group (p < 0.05)38. Li et al. (2023) compared the efficacy of multiple PRP injections versus multiple HA injections in the knee was evaluated by Li et al. (2023) in a recent pooled analysis. Li et al. (2023) analyzed 14 RCTs with 1512 patients. The efficacy of multiple PRP injections was compared with that of multiple HA injections based on VAS, WOMAC, IKDC, or EQ-VAS scores. At 1, 3, 6, and 12 months, multiple PRP injections significantly changed VAS, WOMAC, IKDC, and EQ-VAS scores39. At 3 and 12 months, the VAS score in the group with multiple PRP injections was significantly lower than that in the group with multiple HA injections (P < 0.00001). Furthermore, the WOMAC score in the group with multiple PRP injections was significantly lower than that in the HA multiple injection group at 1, 3, 6, and 12 months (p < 0.01). Meanwhile, the IKDC score significantly increased in the group with multiple PRP injections compared to that in the group with multiple HA injections (p < 0.01) at 3 and 6 months.

Most studies suggest that combining PRP with HA does not result in a higher efficacy than PRP alone. In 2022, a pooled analysis by Zhang et al. (2022) suggested that combining PRP with HA is not better than injecting PRP alone for treating knee osteoarthritis40. Similarly, the study by Nouri et al. (2022) compared the treatment efficacy of using PRP, HA, and combined PRP + HA for hip osteoarthritis and showed that although all three groups improved in pain and joint function, using PRP or PRP combined with HA resulted in higher efficacy than using HA alone; specifically, there was no enhanced efficacy when combining HA with PRP compared to using PRP alone41.

Osteoarthritis occurs at various locations in the body, but the response to osteoarthritis treatment at different locations varies. Indeed, a recent pooled analysis of 24 randomized controlled trials (RCT) with 1344 patients treated for osteoarthritis at different locations, including the knee (KOA), hip (HOA), ankle (AOA), and temporomandibular joint osteoarthritis (TMJOA)42, showed that PRP injections are safe and effective in improving the function of particular locations, especially the knee (KOA), temporomandibular joint (TMKOA), and ankle osteoarthritis (AOA). However, PRP did not effectively reduce pain in patients with hip osteoarthritis (HOA). This observation was similar to that of a previous study by Dong et al. (2020). This study also showed that PRP injections are effective in reducing pain from knee OA, but not from hip osteoarthritis43. This is why Belk et al. (2022) also reported that injecting LP-PRP into patients with hip osteoarthritis resulted in similar efficacy to HA injection44. However, many comprehensive reports on the treatment effect of PRP in hip arthritis contain biases in data collection based on published summaries45.

In treating knee osteoarthritis, injecting PRP into the joint (intra-articular) and the combination of injecting PRP into the joint along with injection into the bone (intraosseous) does not result in a difference in treatment efficacy. The combination of both joint and bone injections does not provide any benefit over joint injection alone for up to 6 months of follow-up in terms of functional improvement and pain reduction46.

Although many studies and analyses have shown that PRP is generally effective in treating osteoarthritis, there is still a group of patients who do not respond to treatment with PRP injections. The first study to explore prognostic factors in treatment response to PRP was recently reported by Ota et al. (2024). Although the study had a relatively small number of patients (36 knee joints), the research group showed a tendency for the impact of the Japanese Knee Injury and Osteoarthritis Outcome Score (J-KOOS) and hyperlipidemia syndrome. Surprisingly, those who responded to PRP treatment had lower J-KOOS scores and hyperlipidemia syndromes47.

Cao et al. (2023) used pharmacodynamic maximal effect models and meta-analysis to show that patients with osteoarthritis with higher symptom scores, older age (≥ 60 years), higher BMI (≥ 30), lower Kellgren-Lawrence degeneration degree (≤ 2), and shorter duration of osteoarthritis (< 6 months) had higher treatment efficacy with PRP48.

Table 1

PRP characteristics	Suggestions
Dose of platelets/joint	> 5.109
Volume of PRP/joint	4-8 mL
Type of PRP	Pure PRP or LP-PRP
Activation status	Activated PRP
Repeated injections	3 injections (monthly)
Knee osteoarthritis grade (Kellgren-Lawrence)	I-III