Understanding Platelet Rich Plasma injections for knee osteoarthritis
- PRP treatments involve collecting a small amount of your blood and spinning it in a centrifuge to separate the platelets from the red cells. The collected platelets are then injected back into the injured area to stimulate healing and regeneration.
- The platelets contain healing agents, or “growth factors.” including Platelet-derived growth factor (PDGF), Transforming growth factor beta (or TGF-β, Insulin-like growth factors, Vascular endothelial growth factor (VEGF) and Epidermal growth factors.
- The number of treatments needed can vary from patient to patient depending on the level of knee degeneration and the level of activity the patient wishes to return to.
Many of the people that have contacted us about their knee pain face the reality that they will need a knee replacement. As most, they have been managing their knee pain with ice packs and heating pads, NSAIDS, such as ibuprofen (Advil, Motrin) or acetaminophen (Tylenol) in increasing doses until they needed a prescription strength dose. Over the years a steady assortment of knee braces and other sleeves and devices found on the internet provided some physical support but not enough to prevent the eventual need for corticosteroid injections and ultimately surgery. Once surgery become the center point of treatment, many people began exploring alternatives.
An introduction to PRP injections
A May 2021 (1) review article, a paper that reviews previously published research, in the International journal of molecular sciences offers an introduction and understanding to the workings of Platelet Rich Plasma in helping people with knee pain and function.
“Knee osteoarthritis represents a clinical challenge due to poor potential for spontaneous healing of cartilage lesions. Several treatment options are available for knee osteoarthritis, including oral nonsteroidal anti-inflammatory drugs, physical therapy, braces, activity modification, and finally operative treatment.
Intra-articular injections are usually used when the non-operative treatment is not effective, and when the surgery is not yet indicated. More and more studies suggesting that Intra-articular injections are as or even more efficient and safe than NSAIDs. Recently, research to improve intra-articular homeostasis has focused on biologic adjuncts, such as platelet-rich plasma (PRP).
The catabolic and inflammatory intra-articular processes that exists in knee osteoarthritis may be influenced by the administration of PRP. PRP can induce a regenerative response and lead to the improvement of metabolic functions of damaged structures. However, the positive effect on chondrogenesis (cartilage growth) and proliferation of mesenchymal stem cells (MSC) is still highly controversial.”
An understanding of how PRP injections can help knee osteoarthritis – as an anti-inflammatory
A September 2022 paper (39) offers a brief explanation of the anti-inflammatory properties of PRP and how these properties can help knee osteoarthritis. Here is the summary: “Two interrelated biological processes fuel early osteoarthritis progression: inflammation and structural tissues catabolism (tissue breakdown). . . In particular, platelet-rich plasma can interfere with inflammation and inflammatory pain. The therapeutic approach is to alter the vicious inflammatory loop by modifying the molecular composition of the synovial fluid, thereby paracrine cellular cross talk (stopping inflammation). Intra-articular injections of platelet-rich plasma can provide key factors balancing proinflammatory and anti-inflammatory factors, targeting macrophage dysfunction and modulating immune mechanisms within the knee. (leaving the good inflammation to do its work of repair).
An understanding of how PRP injections can help knee osteoarthritis – can improve cartilage thickness
A December 2022 paper (43) examine the effectiveness of PRP in creating new knee cartilage thickness and clinical and functional outcomes.
In this paper:
- Thirty patients diagnosed with Kellgren-Lawrence grade II and grade III knees osteoarthritis received three doses of platelet-rich plasma, one dose every seven days.
- Using patient questionnaires and evaluation scales, the researchers found pain and function improved and there was a statistically significant difference in cartilage thickness (femoral and trochlear cartilage) following PRP treatment. The researchers concluded: “This study supports the effectiveness of PRP in the management of osteoarthritis knee by improvement in pain, joint stiffness, and activities of daily living, as well as aids in the repair and regeneration of articular cartilage.”
An Editorial in the journal Arthroscopy April 2021 on Platelet Rich Plasma Injections for knee osteoarthritis
Here is a simple statement from an editorial commentary in the April 2021 issue of the journal Arthroscopy.(2)
“Injections for the pain caused by knee osteoarthritis have been the focus of significant research for the last few decades. Systematic reviews and meta-analyses suggest that platelet-rich plasma (PRP) can provide up to 12 months of pain relief in these patients, superior to both cortisone and hyaluronic acid.”
PRP injections significantly improved pain, stiffness, function, and disability levels compared with the other injection treatments
A study published in January 2021 (3) examined the combined research of 24 previously published studies on the possible benefits of PRP therapy in knee and hip osteoarthritis patients. The findings of this study suggest that PRP injections significantly improved pain, stiffness, function, and disability levels compared with the other injection treatments it was compared against. Intra-articular PRP injection provided better effects than other injections for osteoarthritis patients, especially in knee osteoarthritis patients, in terms of pain reduction and function improvement at short-term follow-up at 1 month, 2 months, 3 months, 6 months, and 12 months.
Research 2022: PRP injections in the knee can alleviate pain symptoms at 3 days after injection.
In our own clinical experience we have seen similar results but these types of results are not seen typically, they are more rare. We find that a multi-treatment PRP plan is usually best for knee osteoarthritis problems. But, pain relief as that described in the 2022 research below can be seen in some.
A January 2022 paper (30) aimed to evaluate the effect of intraarticular injection with platelet-rich plasma on knee osteoarthritis. A total of 250 patients with stages I-III osteoarthritis from December 2018 to June 2020 were included in this study. All the patients had received autologous PRP injection (3 ml) into the affected knee joint every week for totally 3 injections.
The VAS (pain 0-10) score and WOMAC (disability) index were used to evaluate knee function before and at 3 days, 1 month, and 3 months after injection. A total of 250 patients were enrolled in this study, including 130 patients in the PRP group and 120 patients in the control group.
Findings: ” The VAS score and WOMAC index of patients in the PRP group before treatment were not significantly different from those in the control group. At 3 days, 1 month, and 3 months after PRP treatment, the VAS score and WOMAC index of the PRP group were significantly lower than those of the control group. PRP is effective in treatment of knee osteoarthritis. The pain symptoms can be alleviated at 3 days after injection.”
Research 2022: PRP injections in the knee can alleviate pain symptoms at least six months
A May 2022 study (37) evaluated the efficacy and safety of Platelet Rich Plasma (PRP) injections in patients affected by knee osteoarthritis.
- One hundred and fifty-three patients received three consecutive PRP injections and completed follow ups.
- Results: Statistically significant function increase and pain reduction emerged suggesting PRP injection represents a valid conservative treatment to reduce pain, improve quality of life and functional scores even at midterm of 6 months follow-up.
Research: PRP, Intra-articular hyaluronic acid injections and Intra-articular cortisone
A February 2021 (4) study also assed the effectiveness of PRP injections and compared them to cortisone and hyaluronic acid
In addition to providing the growth factors necessary for healing mentioned above, the researchers also noted: “PRP was proven to halt chondrocytes catabolic activity (breakdown and death of cartilage cells), which is important for the reduction of the chondrocyte apoptosis (death) rate, also resulting in a decrease in the loss of the cartilage matrix secreted by cartilage cells and an increase in cartilage height.
The duration of the beneficial effects of PRP injections are unclear, and current evidence indicates that for at least 12 months PRP can improve pain relief and functional improvement in patients with symptomatic knee osteoarthritis, but some (researchers) have described good score values up until 24 months from the beginning of the treatment. Compared to other injective therapies (hyaluronic acid, cortisone, and saline), treatment with PRP was found to be clinically superior in reducing osteoarthritis-related pain symptomatology and increasing the functional outcomes with similar or less risks of adverse events. ”
A September 2022 study (40) assessed and compared the efficacy of different injections used for the treatment of knee osteoarthritis, including hyaluronic acid, corticosteroids, platelet-rich plasma (PRP), and plasma rich in growth factors (PRGF), with a minimum 6-month patient follow-up.
- All injection treatments except corticosteroids were found to result in a statistically significant improvement in outcomes when compared with placebo.
- PRP demonstrated a clinically meaningful difference in function-related improvement when compared with corticosteroids and placebo due to large effect sizes.
- Studies evaluating outcomes of plasma rich in growth factors reported significant improvement when compared with placebo due to large effect sizes, whereas a potential clinically significant difference was detected in the same comparison parameters in pain evaluation.
- With regard to improvements in pain, function, and both combined, PRP was found to possess the highest probability of efficacy, followed by plasma rich in growth factors, hyaluronic acid, corticosteroids and placebo.
Research: PRP, Intra-articular hyaluronic acid injections and Intra-articular cortisone
In a 2019 study in the medical journal Orthopade (5) found that: “Intra-articular PRP injections into the knee for symptomatic early stages of knee osteoarthritis are a valid treatment option. The clinical efficacy of Intra-articular PRP is comparable to that of the Intra-articular hyaluronic acid and Intra-articular cortisone forms after 3 months and the long-term efficacy of Intra-articular PRP is superior to intra-articular hyaluronic acid and Intra-articular cortisone.”
In a September 2019 study in the journal Current reviews in musculoskeletal medicine,(6) doctors wrote:
“Recent clinical studies mainly indicate there may be benefit of PRP usage for the treatment of knee lesions. As an autologous source of bioactive components, PRP has been shown to be typically safe, free of major adverse outcomes. The use of PRP has been continuously increasing, and some well-designed, double-blinded, placebo-controlled clinical trials have been published. Clinical outcomes relating to PRP usage are multifactorial and depend on the severity of the lesion and patient characteristics. Although PRP is safe to use and it can be easily applied in the clinics, case-specific considerations are needed to determine whether PRP could be beneficial or not.”Note: PRP should not be mixed with an anesthetic or intra-articular corticosteroid.”
I sometimes hear from patients that their doctor wanted to mix corticosteroid with their Platelet Rich Plasma injections.
I sometimes hear from patients that their doctor wanted to mix corticosteroid with their Platelet Rich Plasma injections. This is something that we would not do and in fact was a guideline published in June 2020 research in the journal Knee surgery, sports traumatology, arthroscopy.(7) The guideline reached by consensus suggested PRP should not be mixed with an anesthetic or intra-articular corticosteroid. This recommendation was considered appropriate with relative agreement from physicians surveyed.
In this Rush University Medical Center study from August 2021 study (33) younger patients who received injections of PRP, hyaluronic acid and corticosteroid injections were compared for outcomes. The results of this study was “All intra-articular injections treatments except corticosteroid were found to result in a statistically significant improvement in outcomes when compared with placebo. PRP demonstrated a clinically meaningful difference in function-related improvement when compared with corticosteroid and placebo due to large effect sizes.” Finally “With regard to improvements in pain, function, and both combined, PRP was found to possess the highest probability of efficacy.”
Direct comparison between PRP injections and cortisone for knee pain
An October 2020 study (8) compared the effectiveness of platelet-rich plasma in pain complaints reduction and functional improvement of knee osteoarthritis compared with the standard treatment with injectable corticosteroid, such as triamcinolone.
The study was performed on 50 patients with knee osteoarthritis randomly divided into equivalent samples for each therapy (25 patients each).
- At 180 days after treatment the research team was able to verify, through standardized scoring systems that the patients receiving the PRP had reduced pain and better function in their knees.
- In direct comparison between the two treatments the study concludes: “Although both platelet-rich plasma and corticosteroid therapies have been shown to be effective in the reduction pain complaints and functional recovery, there was a statistically significant difference between them at 180 days. According to the results obtained, platelet-rich plasma presented longer-lasting effects within 180 days in the treatment of knee osteoarthritis.”
A June 2021 paper from Queens University Belfast (9) compared intra-articular corticosteroid injections and PRP injections. In this paper while the doctors called corticosteroid injection “the mainstay of treatment for symptomatic management in knee osteoarthritis” the doctors also suggested that platelet-rich plasma injections could be a promising treatment alternative to cortisone.
Doctors examined the case histories of 648 patients and compared the effects of corticosteroid injections and PRP
To demonstrate this the doctors examined the case histories of 648 patients and compared the effects of corticosteroid injections and PRP. The PRP injections showed significantly better in reducing osteoarthritis symptoms at three, six and nine months post-intervention. The greatest effect was observed at six and nine months. At six months PRP allowed greater return to sporting activities than corticosteroid.
The paper concluded: “Intra-articular-PRP injections produce superior outcomes when compared with corticosteroid injections for symptomatic management of knee osteoarthritis, including improved pain management, less joint stiffness and better participation in exercise/sporting activity at 12 months follow-up. ”
Concerns about accelerated knee damage cortisone injections may cause
In December 2020 (10) doctors expressed the concerns of the suggested side-effects that could lead to negative structural outcomes including accelerated osteoarthritis progression, subchondral insufficiency fracture, complications of pre-existing osteonecrosis, and rapid joint destruction (including bone loss) which may be observed in patients who received Intra-articular corticosteroid injections.
In this article we will discuss research on grade 1 to 3 knee osteoarthritis and PRP treatments. When a new patient comes into our office for a consultation for their knee osteoarthritis, we do a careful assessment of the patient and then make recommendations. Sometimes, the lack of range of motion in this patient’s knee and other factors lead us to a recommendation of stem cell injections. This recommendation is based on a realistic expectation of what both treatments may offer. For some, having the PRP only may not offer the healing that they hope to achieve. For others, a surgical option may be a more realistic option.
Use of Platelet Rich Plasma therapy (PRP) for knee osteoarthritis.
A study in the journal Cartilage in June 2020 (11) lays out the benefit of Platelet Rich Plasma therapy with a caution. The variation in how the treatment is offered can be the main factor in the failure or success of treatment. This is a quote from the research:
“PRP injections provide better results than other injectable options. This benefit increases over time, being not significant at earlier follow-ups but becoming clinically significant after 6 to 12 months. However, although substantial, the improvement remains partial and supported by low level of evidence. This finding urges further research to confirm benefits and identify the best formulation and indications for PRP injections in knee osteoarthritis.”
In our office a single PRP treatment may move the injection around the knee to address all the structures in the knee joint capsule. In other offices a single injection is put into the knee at a somewhat arbitrary point. See the video below for how I treated a patient with PRP.
Doctors at the world’s leading medical universities and hospitals are showing that PRP can regenerate damaged knee cartilage and meniscus in patients suffering from knee osteoarthritis and PRP can also enhance healing after knee ligament reconstruction.
An October 2018 study in the journal Current reviews in musculoskeletal medicine (12) says this:
“Recent research into the applications of PRP for knee osteoarthritis has further indicated both the efficacy and safety of PRP treatment. Although research has shown a tendency toward better efficacy at earlier stages of osteoarthritis, evidence exists to indicate positive effects at all stages of osteoarthritis. In summary, since knee osteoarthritis is an extremely prevalent condition that can be a challenge to treat, it is imperative that safe and effective nonoperative treatment methods be available to individuals that are suffering from this condition.”
The researchers here suggested that “Moving forward, it is imperative that future clinical research be conducted in a more standardized manner, ensuring that reproducible methodology is available and minimizing study-to-study variability.”
This study also compared PRP to other conservative care treatments
PRP vs. Exercise
- “Exercise remains one of the first treatments recommended for the treatment of osteoarthritis and has been shown to be a safe, effective method of reducing pain, and improving function in osteoarthritis patients. However, exercise has limitations as a treatment. . . One primary limitation is exercise is associated with poor compliance. Another limitation is exercise can be painful for individuals with osteoarthritis, and it has been shown that is can be challenging for individuals with knee osteoarthritis to regularly exercise.”
- At this current time, the authors are not aware of any research comparing exercise to intra-articular PRP injections however, based on other research, a possible synergistic relationship may exists between exercise therapy and injection therapy.
- Continued NSAID can potentially lead to severe systemic side effects that limit their usefulness of as a long-term treatment method for knee osteoarthritis, such as renal insufficiency, gastritis, peptic ulcer formation, and rare effects with the cardiovascular and cerebrovascular systems. The authors of this study are only aware of one study directly comparing an oral anti-inflammatory and PRP injections. In that study acetaminophen was chosen because it has a lower rate of adverse effects than NSAIDs. PRP injections resulted in significantly better outcomes than did treatment with acetaminophen.
In July 2018, (13) medical university researchers in Ireland lead a multi-national European research team to conclude in their research:
“Platelet-rich plasma therapy is a simple, low-cost and minimally invasive intervention which is feasible to deliver in primary care to treat degenerative lesions of articular cartilage of the knee. This therapy appears to have minimal associated adverse events and may have beneficial effects in terms of pain, health utility, patient satisfaction and goal-orientated outcomes. Further studies, particularly well-designed randomised controlled trials are needed to understand the mechanism of action, establish best practice, and measure outcomes and durability of effect.”
A highlight of these research was the benefit it showed PRP could offer to obese patients:
- The 12 participants in the study had an average age of 72.6 years and average Body Mass Index (SD) of 31.8 meaning that the average person in this study was obese and seven (58%) were male.
- The most common goal of this group was was to be pain free,
- followed by walking normally without aid
- Reduction of knee stiffness
- prevention of knee replacement
- and being able to dance and garden again.
Even a single injection of PRP provided benefit.
In the video below (there is no sound), I demonstrate how why administer PRP. In this case the patient has problems of meniscus degeneration. We apply multiply injections to support regeneration of the whole knee. Below the video is research that suggesting positive results of even a single PRP injection against a single placebo injection.
In November 2017, researchers reported on the benefits of PRP compared to placebo injection in patients who had osteoarthritis in both knees. Published in the American journal of physical medicine & rehabilitation, the study showed PRP treatment significantly improves pain, stiffness, and disability in patients with knee osteoarthritis compared to normal saline (placebo) treatment. Additional strength training is recommended to enhance muscle strength recovery.(14)
PRP is an effective intervention in treating knee osteoarthritis without increased risk of adverse events
Also in November 2017, in the International journal of rheumatic diseases, (15) researchers reported a summary of the most recent findings on the benefits of PRP for knee osteoarthritis. They also wrote about bias in the research:
“Numerous systematic reviews investigating the efficacy of platelet-rich plasma (PRP) in treating knee osteoarthritis have been recently published. The purpose of the present study was (1) to perform an overview of overlapping systematic reviews investigating PRP for knee osteoarthritis via evaluating methodological quality and risk of bias of systematic reviews and (2) to provide recommendations through the best evidence.”
In reviewing the research, the investigators stated that they used a best evidence choice procedure according to the Jadad decision algorithm. (A scales to assess the quality of randomized controlled trials). They wrote: “The systematic reviews with high quality of methodology and low risk of bias were selected ultimately.”
This enabled them to conclude: “The present overview demonstrates that PRP is an effective intervention in treating knee osteoarthritis without increased risk of adverse events. Therefore, the present conclusions may help decision makers interpret and choose PRP with more confidence.”
Platelet Rich Plasma injections (PRP), offers better symptomatic relief to patients with early knee degenerative changes (than hyaluronic acid or placebo)
In the medical journal Arthroscopy, (16) a journal devoted to obviously arthroscopy, surgeons are told that Platelet Rich Plasma injections (PRP), offers better symptomatic relief to patients with early knee degenerative changes (than hyaluronic acid or placebo), and its use should be considered in patients with knee osteoarthritis.
The researchers wrote: “Intra-articular-PRP is a viable treatment for knee OA and has the potential to lead to symptomatic relief for up to 12 months. There appears to be an increased risk of local adverse reactions after multiple PRP injections. Intra-articular-PRP offers better symptomatic relief to patients with early knee degenerative changes, and its use should be considered in patients with knee osteoarthritis.”
This is a verification of early research from the Mayo Clinic which came to the same conclusion – PRP showed better improvement than hyaluronic acid injection and placebo in reducing symptoms and improving function and quality of life. Especially in in younger, active patients with low-grade osteoarthritis.(17)
This is from the Mayo Clinic research:
“Intraarticular platelet-rich plasma (PRP) injection has emerged as a promising treatment for knee osteoarthritis. Studies to date, including multiple randomized controlled trials, have shown that PRP is a safe and effective treatment option for knee osteoarthritis. Intraarticular PRP is similar in efficacy to hyaluronic acid, and seems to be more effective than hyaluronic acid in younger, active patients with low-grade osteoarthritis. Treatment benefits seem to wane after 6-9 mos. There are numerous PRP treatment variables that may be of importance, and the optimal PRP protocol remains unclear.”
One shot of PRP against one shot of Hyaluronic Acid
A September 2021 (18) comparative study looked at 10 patients who underwent intra-articular PRP injection and 10 others received Hyaluronic Acid injection.
- At baseline (pre-injection) visit and one, three, six, and 12 months post-injection, clinical assessments were performed using visual analogue scale (VAS) and Knee injury and Osteoarthritis Outcome Score (KOOS) questionnaire. Physical examinations of the knee, including crepitation and range of motion (ROM) were performed at each visit. The follow-up responses were compared with the baseline visit.
Results: The PRP treatment was ascertained to be safe and caused no adverse effects. Significant improvements in the majority of KOOS subscales and VAS were found throughout the entire 12-month follow-up, following the PRP injections.
Hyaluronic Acid injection, however, caused only one month significant improvement in the majority of patient-reported outcomes. In the majority of visits, the extent of improvements in the scores of KOOS subscales, as well as the extent of reduction in VAS were significantly greater in PRP recipients, compared to Hyaluronic Acid injection recipients. The ROM in both groups slightly increased after interventions.
Conclusion: Intra-articular injection of PRP or Hyaluronic Acid alleviates symptoms and pain and improves functionality and physical examinations in patients with knee osteoarthritis. However, PRP therapy produces greater and longer-lasting improvements in most of the outcome parameters compared to Hyaluronic Acid.
More research on PRP and hyaluronic acid injections
An August 2022 paper (29) looked at the combined research of thirty-three different studies which included data on 7003 patients knee osteoarthritis patients. Five therapeutic treatments were analyzed.
- Meta-analysis showed that the efficacy of platelet-rich plasma injection was superior to both ozone and hyaluronic acid therapies.
- Hyaluronic acid + ozone and platelet-rich plasma + hyaluronic acid were both superior to ozone and hyaluronic acid monotherapy.
- Platelet-rich plasma + hyaluronic acid, hyaluronic acid + ozone compared with 3 monotherapies (platelet-rich plasma, ozone, hyaluronic acid) were statistically significant, except for the difference in efficacy with platelet-rich plasma, which was not statistically significant.
- Also, the efficacy of platelet-rich plasma was better than hyaluronic acid and ozone and the difference was statistically significant, indicating that platelet-rich plasma was more effective than ozone and sodium glass in the treatment of osteoarthritis of the knee in monotherapy.
Is PRP a “one and done” treatment? For some yes, for many NO
When we see a new patient with degenerative knee disease who had “failed” PRP treatments at other clinics, we ask them how many treatments did they have? More often than not they say “one injection.” For some with minor osteoarthritis, as pointed out by the medical studies highlighted in this article, one injection provides benefit. But one injection may not be sufficient for someone who has a more active lifestyle than others.
A June 2021 paper (19) investigated the effectiveness of a single intraarticular PRP injection for patients with early knee osteoarthritis. In this study forty-one patients with knee osteoarthritis (Kellgren-Lawrence grade 1-2) received a single PRP injection into the target knee and were assessed at baseline and one, three, and six months post-injection.
- The prime measurement of treatment success was pain reduction
- Secondary was function, reduction of pain medications and if the patient was happy with the treatment.
- The average pain scores decreased significantly at one, three, and six months post-injection. Patients’ satisfaction was high. No serious adverse events occurred.
“One injection of PRP improved pain and function for six months for patients with early knee osteoarthritis. This study supports putting the one-injection regimen into clinical practice.”
Research on two PRP injections
Here is a recent study where the patients received two PRP injections as the complete PRP treatment program. This treatment group was considered to be “active.” This research was published in the journal Sports Health.(20)
- Fifty patients with knee osteoarthritis were followed for a minimum of 12 months.
- All were treated with 2 intra-articular injections of autologous PRP.
- Twenty-five patients had undergone a previous operative intervention for cartilage lesions, whereas 25 had not.
- Note – 25 of the 50 patients had some type of surgical procedure on their knee before their first PRP treatment. Operated patients had undergone either cartilage shaving or microfracture.
- All patients (even the ones with past knee arthroscopic procedure) showed significant improvement in all testing and measurement scores for pain and function at 6 and 12 months and returned to previous activities.
This research concludes: “PRP represents a user-friendly therapeutic application that is well tolerated and shows encouraging preliminary clinical results in active patients with knee osteoarthritis. Patients who underwent previous cartilage shaving and/or microfractures also showed favorable results, indicating that PRP could be an additional therapy for these patients. Standardization of PRP protocols, long-term follow-up, and prospective blinded randomized studies should clarify questions regarding PRP effectiveness and durability of clinical improvement.”
Research on three PRP injections
A paper published in the Journal of physical therapy science.(21) It comes from doctors working in medical university hospitals in Turkey.
- One of the major results of this study was the effectiveness of PRP treatment for pain and physical function in grade 3 knee osteoarthritis.
- The effectiveness of a single injection was found to be significantly lower than that of two or three injections.
- 3 PRP injections separated by 2-week intervals were found to be more effective for the improvement of pain and mobility than 2 injections in Grade 3 osteoarthritis patients
- A significant effect was observed in the early period after a single injection of PRP, but the effect decreased in a short time. Based on the present results, we recommend 2 or 3 injections of PRP for patients with moderate knee osteoarthritis, and physicians’ decisions should be based on various factors such as the level of pain, level of activity, cost-effectiveness, and Body Mass Index
- We further speculate that repeating the application after 6 months may further relieve symptoms for a longer period and delay osteoarthritis progression.
The researchers concluded their research by saying:
“The strength of this study was the prospective randomized design. The absence of a control group and the relatively small patient numbers were the limitations of the study. Considering the evidence, this minimally invasive injection procedure appears to be safe and effective, and since PRP injections biologically change the articular cartilage, they may be a worthwhile treatment option even in moderate knee osteoarthritis. Further studies are required with larger sample sizes with longer follow-ups and objective outcome measures. In conclusion, PRP is an effective and reliable treatment for functional status and pain for Grade 3 osteoarthritis, and a minimum of two injections appears to be appropriate.”
An October 2022 paper (41) sought “to prove the efficacy of PRP injection therapy on knee pain and functions by comparing patients with mild to moderate osteoarthritis with a placebo control group, and also to understand the effectiveness of multiple doses compared to a single dose. It was hypothesized that PRP would lead to more favorable results than the placebo at one, three, six, 12 and 24 months after treatment.”
In this study, 237 osteoarthritis patients were broken up into four groups.
- Single dose of PRP
- single dose of sodium saline
- three doses of PRP
- and three doses of sodium saline.
In comparison to the placebo, leukocyte-rich PRP treatment was determined to be effective in the treatment of osteoarthritis. Multiple doses of PRP increase the treatment efficacy and duration. Of all the patients treated with PRP, the best results were obtained by patients aged 51-65 years
In comparison to the placebo, PRP treatment was determined to be effective in the treatment of osteoarthritis. Multiple doses of PRP increase the treatment efficacy and duration.
Most recently an October 2021 study (22) compared single and multiple doses of PRP against each other and against placebo. The researchers of this study set out to demonstrate the effectiveness of PRP injection therapy on knee pain and functions by comparing patients with mild to moderate osteoarthritis with a placebo control group, and also to understand the effectiveness of multiple doses compared to a single dose. They also hypothesized that PRP would lead to more favorable results than the placebo at 1, 3, 6, 12 and 24 months after treatment.
- 237 patients diagnosed with osteoarthritis were randomly separated into 4 groups, who were administered the following:
- single dose of PRP
- single dose of sodium saline (placebo)
- three doses of PRP
- and three doses of sodium saline (placebo).
- Clinical evaluations were made pre-treatment and at 1, 3, 6, 12 and 24 months post-treatment, using the Knee Injury and Osteoarthritis Result Score (KOOS), Kujala Patellofemoral Score, knee joint range of motion (ROM), measurements of knee circumference (KC), and mechanical axis angle (to measure bow-knee or knock-knee angles) and a Visual Analog Scale (VAS) for the evaluation of pain.
- Patients treated with PRP maintained better scores at 3, 6 and 12 months compared to the the placebo groups
- Multiple doses of PRP were seen to be more effective than single-dose PRP at 6 and 12 months.
- At the end of 24 months, there was no significant score difference across all the groups. The most positive change in scores was found in stage 2 osteoarthritis, and the most positive change in ROM was in stage 3 osteoarthritis patients.
Conclusion: In comparison to the placebo, PRP treatment was determined to be effective in the treatment of osteoarthritis. Multiple doses of PRP increase the treatment efficacy and duration. Of all the patients treated with PRP, the best results were obtained by patients aged 51-65 years, with lower mechanical axis angle, and by stage 2 osteoarthritis patients.
Research: One PRP treatment effective for pain, multiple PRP treatment effective for function
In the December 2019 issue of Orthopaedic journal of sports medicine (23), researchers examined previously performed studies on the effectiveness of PRP as to compare the effectiveness of a single PRP treatment vs. multiple PRP treatments in patients with knee osteoarthritis. Five studies that included 301 patients suggested that:
- At 6 months after the PRP treatment, single and multiple (double or triple) injections had similar pain improvement, with no significant differences
- A significant improvement in knee functionality was observed in favor of multiple injections
- According to these results, a single injection was as effective as multiple PRP injections in pain improvement; however, multiple injections seemed more effective in joint functionality than a single injection at 6 months.
Benefit can be had in Stage I to Stage IV knee osteoarthritis
A January 2022 study (31) examined the effectiveness in Stage I, II, III, IV knee osteoarthritis. “Reports have concluded that platelet-rich plasma (PRP) is an effective and safe biological approach to treating knee osteoarthritis. However, the effectiveness of PRP in advanced stages of the disease is not entirely clear. The purpose of this study was to evaluate whether the use of PRP would be as effective in studies with early-moderate knee osteoarthritis patients compared to studies including patients with end-stage osteoarthritis.” Included in this study was 31 clinical trials that reported data of 2705 subjects. Meta-analysis revealed an overall significant improvement of both pain and function favoring PRP. Subanalysis for pain and functional improvement showed a significant pain relief in studies with stage I to stage III and stage 1 to IV osteoarthritis and a significant functional improvement in studies with stage I, II, III, and IV osteoarthritis.
Stem cell therapy versus PRP Injections
A May 2022 paper (36) compared research outcomes for the following treatments: platelet-rich plasma (PRP); bone marrow-derived mesenchymal stem cells; adipose-derived mesenchymal stem cells and amniotic-derived mesenchymal stem cells. In all eighty-two research studies were included. The researchers had difficulty making comparisons because of inconsistencies in preparation of the injection solutions. In general the studies on all treatments pointed to more fair to good outcomes in most patients.
One injection of bone marrow stem cells versus one injection of PRP
Let’s summarize this article with a new study comparing bone marrow derived stem cell therapy and PRP therapy. As noted above in the research, one injection of PRP typically does not meet the patient goal of treatment, whether it is less pain or greater function. A January 2022 study (24) in comparing bone marrow derived stem cell therapy vs. PRP, one shot vs one shot found bone marrow aspirate concentrate significantly outperformed the PRP injection. This is something we would expect to see. The researchers of this study concluded: “Intra-articular autologous BMAC injections are safe, effective in treating pain, and ameliorate functionality in patients with symptomatic knee osteoarthritis to a greater extent than PRP injections. Intra-articular autologous BMAC therapy is safe and provides more relief to patients with symptomatic knee osteoarthritis compared to PRP therapy.”
When PRP treatment may fail? The knee is too far gone or patient is overweight.
Above I discussed why PRP may fail citing typically the patient did not get enough treatments, PRP is usually not effective as a one injection, one treatment remedy. But there are more reasons. An August 2021 review study (25) reported on the 5-year clinical effectiveness of PRP intra articular injections in knee osteoarthritis and investigated the risk factors for predictive treatment failure and poor clinical outcome. In this case review 118 patients treated for low to moderate knee osteoarthritis demonstrated by X-Ray and magnetic resonance imaging (MRI) with autologous PRP injection from 2014 to 2018 with an average plus four year follow up. Results: There was a significant improvement of all outcome measures at final follow-up and high satisfaction rate (79.7%) with the PRP treatments for knee pain. The overall failure rate was of 15.3% after an average 57 month follow up. Being overweight and advanced osteoarthritis were identified as significant independent risk factor related to failure of autologous PRP injection.
Conclusion: Intra articular PRP injections led to a significant clinical improvement in middle-aged adults with a low to moderate knee osteoarthritis. Body Mass Index and advanced degenerative knee disease have been identified as significant risk factors predictive for failure at mid-term follow-up.
Research for athletes
Below is what doctors are saying to each other about athletes who want to stay active. It was published in the medical journal Cartilage: “As a result of the complexity of the arthritic knee, athletes, particularly those with a history of knee injury, have an earlier onset and higher prevalence of osteoarthritis. This can present a clinical dilemma to the physician managing the patient who, despite the presence of radiologically confirmed disease, has few symptoms and wishes to maintain an active lifestyle.”(26)
The difficulty or “challenge” is in the prevention of advancing of knee osteoarthritis. Here the typical recommendations of anti-inflammatory medications, knee braces, and ice, those that the athlete can impose upon themselves, will lead to further knee deterioration. It is a challenge to convince an athlete of this when it may get them on the course, track of field this weekend.
In a recent study, researchers at Hospital for Special Surgery gave patients with early osteoarthritis an injection of PRP (6-mL), and then monitored them for one year. At baseline and then one year after the PRP injection, physicians evaluated the knee cartilage with magnetic resonance imaging (MRI). While previous studies have shown that patients with osteoarthritis can lose roughly five percent of knee cartilage per year, the Hospital for Special Surgery investigators found that a large majority of patients in their study had no further cartilage loss. At minimum PRP prevented further knee deterioration.
Research for overweight or obese patients
Weight loss can protect you from the need for a knee replacement. This should not be news to you. People who are overweight understand that their arthritis related knee problems can be made worse because of their weight. The news you are probably looking for is a way to lose that weight. In the end we can recommend a low carb / hi lean protein diet for you, but while that may be a great diet plan for you, it is still your ability to motivate yourself to lose the weight that will make it happen. I know that what many of you do not need is another doctor or article that lectures you about being overweight. What you may need is some motivation by way of knowledge. Understanding what weight does to your knee and understanding what weight loss does in helping your knee may be the path to your motivation.
A March 2020 study (27) compared the effectiveness in pain relief and increased function of PRP injections and hyaluronic acid injections for overweight or obese patients who suffered from knee osteoarthritis. The researchers noted that during the first two months of follow-up, there was no significant difference between PRP injections and hyaluronic acid injections in terms of effectiveness in the two groups. At the third, sixth, and 12th months of follow-up, the pooled analysis of the data they were examining showed that PRP injections was more effective than hyaluronic acid for the treatment of knee osteoarthritis in overweight or obese patients.
Before and After MRI following PRP knee injections
Often people will email us asking if we have documented MRI evidence that cartilage or meniscus had regrown during PRP treatment. Success of PRP treatment is empirical. In other words, how does the patient feel after treatment. For someone who had success, they usually do not need an after MRI image to tell them that they have less pain and more function in their knee. Further, few people will get an AFTER MRI because of the expense of the test.
Let’s look at a January 2020 study in the Journal of pain research.(28) Here the point of the study was AFTER MRI.
“In this double blind randomized clinical trial, patients with bilateral knees osteoarthritis-grade 1, 2, and 3 were included in the study. Each patient’s knees were randomly allocated to either control or treatment groups. PRP was injected in two sessions with 4 week intervals in PRP group. The VAS (visual analog scale) and WOMAC (Western Ontario and McMaster Universities Arthritis Index) were utilized and MRI was performed for all patients, before, and 8 months after treatment.”
“46 knees (from 23 patients) were included in this study. 23 knees in the case group and 23 knees in control group were studied. All patients were female with mean age of 57.5 (range about 54 to 60.5) years.
“In PRP group, all of the radiologic variables (patellofemoral cartilage volume, synovitis and medial and lateral meniscal disintegrity), with the exception of subarticular bone marrow abnormality, had significant improvement. In a comparison between the two groups, patellofemoral cartilage volume and synovitis had significantly changed in the PRP group.”
Conclusion: “In this study, in addition to the effect of PRP on VAS and WOMAC, there was a significant effect on radiologic characteristics (patellofemoral cartilage volume and synovitis). For further evaluation, a longer study with a larger sample size is recommended.”
What are PRP or Platelet-Rich Plasma Injections and how can they help issues of chronic knee pain?
- PRP treatments involve collecting a small amount of your blood and spinning it in a centrifuge to separate the platelets from the red cells. The collected platelets are then injected into the knee to stimulate healing and regeneration.
- PRP Injection Therapy is designed to rebuild cartilage, repair torn meniscus and ligaments, and reduce swelling and pain. In the hands of an experienced clinician, it can help delay joint replacement, help certain patients avoid a surgery. It works by stimulating the natural immune repair mechanisms and supplying the growth factors necessary to build tissue.
- PRP injection are designed to deliver high concentration of endogenous (your own “home-grown”) platelets to the knee where osteoarthritis is present.
- Because platelets play a significant role in the healing of tissue, reintroducing a high concentration of platelets directly into the injured area may enhance the healing process.
How effective is it? “Predicting the effectiveness of platelet-rich plasma therapy remains uncertain.”
In our office we seek to offer realistic assessments of how effective PRP may be for a patient. A main reason that PRP may not work is that the person is very active or has a physically demanding line of work and the treatment is not allowed to take hold. Screening is important as we try to determine before treatment the likelihood that the person seeking treatment will have a degree of success.
A September 2021 study (29) including 517 consecutive patients who underwent three injections of platelet-rich plasma therapy found “patient-oriented outcomes were significantly improved 6 and 12 months after platelet-rich plasma therapy. The overall responder rate in patients who met the Outcome Measures in Rheumatology (OMERACT)-Osteoarthritis Research Society International (OARSI) responder criteria was 62.1%. (This is a patient response survey).
- The responder rate was significantly lower in patients with severe knee osteoarthritis (stage 4, 50.9%) than in those with mild (stage 2 , 75.2%) and moderate (stage 3, 66.5%) knee osteoarthritis.
- The deterioration of the knee osteoarthritis grade (worsening grade) was a significant predictor of a worse clinical outcome.
- The efficacy of platelet-rich plasma therapy was not affected by age, sex, body weight, or platelet count.
- This study revealed that the effectiveness of platelet-rich plasma therapy for the treatment of knee osteoarthritis is approximately 60% and that the effectiveness depends on the severity of knee osteoarthritis.
Research on PRP and the progression of knee osteoarthritis
In a July 2020 study, doctors in the journal International orthopaedics (34) suggested that PRP treatment could slow down osteoarthritis progression, resulting in a delay of knee replacement. 74.1% of the patients in the retrospective study achieved a delay in the total knee replacement of 5.3 years. The study showed that 85.7% of the patients did not undergo total knee replacement during the five year follow-up.
The latest research findings
A March 2022 study (32) reviewed the current medical literature in comparing PRP with the most used and studied injections including hyaluronic acid, corticosteroid, and saline.
- What the researchers found was that “PRP was as effective as and in some studies more effective than other therapies regarding pain, function, and stiffness. However, current evidence is of low or very low quality and is based on trials with high risk of bias and great heterogeneity among them. No significant difference among treatments was found concerning major adverse events and treatment failure.
- Conclusion: “Although studies suggest that PRP may be more effective than or at least as effective as other modalities of nonsurgical treatment for knee osteoarthritis in terms of pain, function, and adverse events, serious limitations and methodological flaws are considerable in the current literature. Therefore, the authors are not able to make recommendations for clinical practice regarding PRP for knee osteoarthritis.”
An April 2022 study (35) compared platelet-rich plasma and triamcinolone hexacetonide or saline solution injection in knee osteoarthritis as a double blinded randomized controlled trial with one year follow-up. Each patient received one injection.
- Patients were assessed at baseline and after four, eight, twelve and 52 weeks with: visual analogue scale (VAS) for pain at rest and movement, WOMAC (pain and function) questionnaire, Timed to Up and Go test, 6-min walk test, percentage of improvement, goniometry (range of motion), and quality of life questionnaire, among others.
Results: 100 patients were studied, with an average age of 67. The triamcinolone hexacetonide group was superior for: percentage of improvement (versus saline solution group from 4 to 52 weeks); WOMAC total and pain (versus PRP group at 4 weeks); and WOMAC stiffness (versus saline solution group at 12 weeks).
Conclusion: The Triamcinolone Hexacetonide group was superior for percentage of improvement and WOMAC, pain and stiffness. For the WOMAC function, the Platelet-Rich Plasma group and Triamcinolone Hexacetonide group were superior to the Saline group. The Platelet-Rich Plasma group showed the lowest radiographic progression at 52 weeks of follow-up. (The PRP group slowed the progression of the knee joint disease better than the other injections). This was a single injection of PRP.
Is this treatment right for you?
No treatment works for everyone all of the time. When considering PRP injections for your knee pain a doctor knowledgeable in physical examinations of your knee function would be more beneficial in most cases than those doctors treating what they see on an MRI. Also, look for doctors experienced in offering this treatment. In the end, PRP injections are considered controversial by some, mostly because of the lack of standardization in the preparation and administering of this treatment. A January 2023 paper (42) also addressed these issues by writing: “While many controversies remain on the best PRP formulation, the overall available clinical studies support the benefits of PRP, with functional improvement and reduction of pain-related symptoms up to 12 months, especially in young patients and early osteoarthritis stages.”
Again, what all this research shows is that for the best chance for PRP to work for your knee pain, you need a doctor experienced in offering the treatment. PRP injection is not cortisone, it is a growth and repair mechanism and as such requires observation after treatment, adjustments after treatment, supportive treatments to treat the whole. A single injection of PRP will offer lead to non-conclusive results – people in pain need a “conclusion.” The results of PRP injections can vary greatly. Research studies suggest that PRP injections can be effective at relieving knee pain and quickly returning patients to their normal routine. Research has also demonstrated both through ultrasound and MRI images tissue repair after PRP treatments.
How long does PRP take to work?
In the research above, doctors suggest that PRP benefit could be seen in as little as three days. That is possible however a more realistic view would suggest an initial improvement seen within a few weeks. This improvement would also have to be gauged against the severity of the injury.
I hope this article will give you a good understanding of how PRP works and how it may compare against other treatments. PRP does not work for everyone. Will it work for you? That answer comes best when explored on an individual basis, following a physical examination, and, when we have the opportunity to sit down together and discuss what are your goals of treatment. If you have questions about your candidacy for treatment. Email me.
1 Szwedowski D, Szczepanek J, Paczesny Ł, Zabrzyński J, Gagat M, Mobasheri A, Jeka S. The Effect of Platelet-Rich Plasma on the Intra-Articular Microenvironment in Knee Osteoarthritis. International Journal of Molecular Sciences. 2021 Jan;22(11):5492.
2 Karasavvidis T, Totlis T, Gilat R, Cole BJ. Platelet-rich plasma combined with hyaluronic acid improves pain and function compared with hyaluronic acid alone in knee osteoarthritis: A systematic review and meta-analysis. Arthroscopy: The Journal of Arthroscopic & Related Surgery. 2020 Dec 3.
3 Dong Y, Zhang B, Yang Q, Zhu J, Sun X. The effects of platelet-rich plasma injection in knee and hip osteoarthritis: a meta-analysis of randomized controlled trials. Clinical Rheumatology. 2020 Jun 12:1-5.
4 Testa G, Giardina SM, Culmone A, Vescio A, Turchetta M, Cannavò S, Pavone V. Intra-Articular Injections in Knee Osteoarthritis: A Review of Literature. Journal of Functional Morphology and Kinesiology. 2021 Mar;6(1):15.
5 Huang Y, Liu X, Xu X, Liu J. Intra-articular injections of platelet-rich plasma, hyaluronic acid or corticosteroids for knee osteoarthritis. Der Orthopäde. 2019 Jan 8:1-8.
6 Cengiz IF, Pereira H, Espregueira-Mendes J, Reis RL, Oliveira JM. The Clinical Use of Biologics in the Knee Lesions: Does the Patient Benefit? Curr Rev Musculoskelet Med. 2019 Jun 28;12(3):406-414. doi: 10.1007/s12178-019-09573-3. [Epub ahead of print]. PMID: 31254255; PMCID: PMC6684695.
7 Eymard F, Ornetti P, Maillet J, et al. Intra-articular injections of platelet-rich plasma in symptomatic knee osteoarthritis: a consensus statement from French-speaking experts [published online ahead of print, 2020 Jun 24]. Knee Surg Sports Traumatol Arthrosc. 2020;10.1007/s00167-020-06102-5. doi:10.1007/s00167-020-06102-5
8 Freire MR, da Silva PM, Azevedo AR, Silva DS, da Silva RB, Cardoso JC. Comparative effect between infiltration of platelet-rich plasma and the use of corticosteroids in the treatment of knee osteoarthritis: a prospective and randomized clinical trial. Revista Brasileira de Ortopedia. 2020 Oct;55(5):551-6.
9 McLarnon M, Heron N. Intra-articular platelet-rich plasma injections versus intra-articular corticosteroid injections for symptomatic management of knee osteoarthritis: systematic review and meta-analysis. BMC Musculoskelet Disord. 2021 Jun 16;22(1):550. doi: 10.1186/s12891-021-04308-3. PMID: 34134679.
10 Guermazi A, Neogi T, Katz JN, Kwoh CK, Conaghan PG, Felson DT, Roemer FW. Intra-articular Corticosteroid Injections for the Treatment of Hip and Knee Osteoarthritis-related Pain: Considerations and Controversies with a Focus on Imaging—Radiology Scientific Expert Panel. Radiology. 2020 Dec;297(3):503-12.
11 Filardo G, Previtali D, Napoli F, Candrian C, Zaffagnini S, Grassi A. PRP Injections for the Treatment of Knee Osteoarthritis: A Meta-Analysis of Randomized Controlled Trials [published online ahead of print, 2020 Jun 19]. Cartilage. 2020;1947603520931170. doi:10.1177/1947603520931170
12 Cook CS, Smith PA. Clinical Update: Why PRP Should Be Your First Choice for Injection Therapy in Treating Osteoarthritis of the Knee. Curr Rev Musculoskelet Med. 2018 Oct 22. doi: 10.1007/s12178-018-9524-x.
13 Glynn LG, Mustafa A, Casey M, et al. Platelet-rich plasma (PRP) therapy for knee arthritis: a feasibility study in primary care. Pilot Feasibility Stud. 2018;4:93. Published 2018 Jul 4. doi:10.1186/s40814-018-0288-2
14 Wu YT, Hsu KC, Li TY, Chang CK, Chen LC. Effects of platelet-rich plasma on pain and muscle strength in patients with knee osteoarthritis. American journal of physical medicine & rehabilitation. 2017 Nov.
15 Xing D, Wang B, Zhang W, Yang Z, Hou Y, Chen Y, Lin J. Intra‐articular platelet‐rich plasma injections for knee osteoarthritis: An overview of systematic reviews and risk of bias considerations. International journal of rheumatic diseases. 2017 Dec 5.
16 Campbell KA, Saltzman BM, Mascarenhas R, Khair MM, Verma NN, Bach BR Jr, Cole BJ. A Systematic Review of Overlapping Meta-analyses. Arthroscopy. 2015 Nov;31(11):2213-21. doi: 10.1016/j.arthro.2015.03.041. Epub 2015 May 29.
17 Pourcho AM, Smith J, Wisniewski SJ, Sellon JL.Intraarticular platelet-rich plasma injection in the treatment of knee osteoarthritis: review and recommendations. Am J Phys Med Rehabil. 2014 Nov;93(11 Suppl 3):S108-21. doi: 10.1097/PHM.0000000000000115.
18 Jivan SJ, Monzavi SM, Zargaran B, Alamdari DH, Afshari JT, Etemad-Rezaie A, Sakhmaresi TA, Shariati-Sarabi Z. Comparative analysis of the effectiveness of intra-articular injection of platelet-rich plasma versus hyaluronic acid for knee osteoarthritis: results of an open-label trial. Archives of Bone and Joint Surgery. 2021 Sep;9(5):487.
19 Sun SF, Hsu CW, Lin HS, Liou I, Chou YC, Wu SY, Huang HY. A single intraarticular platelet-rich plasma improves pain and function for patients with early knee osteoarthritis: Analyses by radiographic severity and age. Journal of Back and Musculoskeletal Rehabilitation. 2021 Jun 4(Preprint):1-0.
20 Gobbi A, Karnatzikos G, Mahajan V, Malchira S. Platelet-rich plasma treatment in symptomatic patients with knee osteoarthritis: preliminary results in a group of active patients. Sports Health. 2012;4(2):162-72.
21 Kavadar G, Demircioglu DT, Celik MY, Emre TY. Effectiveness of platelet-rich plasma in the treatment of moderate knee osteoarthritis: a randomized prospective study. J Phys Ther Sci. 2015 Dec;27(12):3863-7. doi: 10.1589/jpts.27.3863. Epub 2015 Dec 28.
22 Yurtbay A, Say F, Çinka H, Ersoy A. Multiple platelet-rich plasma injections are superior to single PRP injections or saline in osteoarthritis of the knee: the 2-year results of a randomized, double-blind, placebo-controlled clinical trial. Archives of Orthopaedic and Trauma Surgery. 2021 Oct 27:1-4.
23 Vilchez-Cavazos F, Millán-Alanís JM, Blázquez-Saldaña J, Álvarez-Villalobos N, Peña-Martínez VM, Acosta-Olivo CA, Simental-Mendía M. Comparison of the Clinical Effectiveness of Single Versus Multiple Injections of Platelet-Rich Plasma in the Treatment of Knee Osteoarthritis: A Systematic Review and Meta-analysis. Orthop J Sports Med. 2019 Dec 16;7(12):2325967119887116. doi: 10.1177/2325967119887116. PMID: 31897409; PMCID: PMC6918503.
24 El-Kadiry AE, Lumbao C, Salame N, Rafei M, Shammaa R. Bone marrow aspirate concentrate versus platelet-rich plasma for treating knee osteoarthritis: a one-year non-randomized retrospective comparative study. BMC Musculoskeletal Disorders. 2022 Dec;23(1):1-4.
25 Alessio-Mazzola M, Lovisolo S, Sonzogni B, Capello AG, Repetto I, Formica M, Felli L. Clinical outcome and risk factor predictive for failure of autologous PRP injections for low-to-moderate knee osteoarthritis. J Orthop Surg (Hong Kong). 2021 May-Aug;29(2):23094990211021922. doi: 10.1177/23094990211021922. PMID: 34180298.
26 Kirkendall DT. Management of the Retired Athlete with Osteoarthritis of the Knee. Cartilage January 2012 vol. 3 no. 1 suppl 69S-76S
27 Luo P, Xiong Z, Sun W, Shi L, Gao F, Li Z. How to Choose Platelet-Rich Plasma or Hyaluronic Acid for the Treatment of Knee Osteoarthritis in Overweight or Obese Patients: A Meta-Analysis. Pain Res Manag. 2020 Mar 10;2020:7587936.
28 Raeissadat SA, Ghorbani E, Sanei Taheri M, Soleimani R, Rayegani SM, Babaee M, Payami S. MRI Changes After Platelet Rich Plasma Injection in Knee Osteoarthritis (Randomized Clinical Trial). J Pain Res. 2020 Jan 10;13:65-73. doi: 10.2147/JPR.S204788. PMID: 32021396; PMCID: PMC6959502.
29 Saita Y, Kobayashi Y, Nishio H, Wakayama T, Fukusato S, Uchino S, Momoi Y, Ikeda H, Kaneko K. Predictors of Effectiveness of Platelet-Rich Plasma Therapy for Knee Osteoarthritis: A Retrospective Cohort Study. Journal of Clinical Medicine. 2021 Jan;10(19):4514.
30. Zhang B, Yu J, Fan D, Bao L, Feng D. Effect of Intraarticular Injection of Platelet-Rich Plasma on Knee Osteoarthritis: A Multicenter Retrospective Clinical Study. Journal of Healthcare Engineering. 2022 Jan 7;2022.
31. Vilchez-Cavazos F, Blázquez-Saldaña J, Gamboa-Alonso A, Peña-Martínez V, Acosta-Olivo C, Sánchez-García A, Simental-Mendía M. The use of platelet-rich plasma in studies with early knee osteoarthritis versus advanced stages of the disease: a systematic review and meta-analysis of 31 randomized clinical trials.
32 Costa LA, Lenza M, Irrgang JJ, Fu FH, Ferretti M. How Does Platelet-Rich Plasma Compare Clinically to Other Therapies in the Treatment of Knee Osteoarthritis? A Systematic Review and Meta-analysis. The American Journal of Sports Medicine. 2022 Mar 22:03635465211062243. [Google Scholar]
33 Singh H, Knapik DM, Polce EM, Eikani CK, Bjornstad AH, Gursoy S, Perry AK, Westrick JC, Yanke AB, Verma NN, Cole BJ. Relative Efficacy of intra-articular injections in the treatment of knee osteoarthritis: a systematic review and network meta-analysis. The American journal of sports medicine. 2021 Aug 17:03635465211029659.
34 Sánchez M, Jorquera C, Sánchez P, Beitia M, García-Cano B, Guadilla J, Delgado D. Platelet-rich plasma injections delay the need for knee arthroplasty: a retrospective study and survival analysis. Int Orthop. 2020 Jul 3. doi: 10.1007/s00264-020-04669-9.
35 Nunes-Tamashiro JC, Natour J, Ramuth FM, Toffolo SR, Mendes JG, Rosenfeld A, Furtado RN. Intra-articular injection with platelet-rich plasma compared to triamcinolone hexacetonide or saline solution in knee osteoarthritis: A double blinded randomized controlled trial with one year follow-up. Clinical Rehabilitation. 2022 Apr 4:02692155221090407.
36 Delanois RE, Sax OC, Chen Z, Cohen JM, Callahan DM, Mont MA. Biologic Therapies for the Treatment of Knee Osteoarthritis: An Updated Systematic Review. The Journal of Arthroplasty. 2022 May 21.
37 Moretti L, Maccagnano G, Coviello M, Cassano GD, Franchini A, Laneve A, Moretti B. Platelet Rich Plasma Injections for Knee Osteoarthritis Treatment: A Prospective Clinical Study. Journal of Clinical Medicine. 2022 May 8;11(9):2640.
38 Lin X, Zhi F, Lan Q, Deng W, Hou X, Wan Q. Comparing the efficacy of different intra-articular injections for knee osteoarthritis: A network analysis. Medicine. 2022 Aug 8;101(31).
39 Andia I, Atilano L, Maffulli N. Biological Targets of Multimolecular Therapies in Middle-Age Osteoarthritis. Sports Medicine and Arthroscopy Review. 2022 Sep 3;30(3):141-6.
40 Singh H, Knapik DM, Polce EM, Eikani CK, Bjornstad AH, Gursoy S, Perry AK, Westrick JC, Yanke AB, Verma NN, Cole BJ. Relative efficacy of intra-articular injections in the treatment of knee osteoarthritis: a systematic review and network meta-analysis. The American journal of sports medicine. 2021 Aug 17:03635465211029659.
41 Yurtbay A, Say F, Çinka H, Ersoy A. Multiple platelet-rich plasma injections are superior to single PRP injections or saline in osteoarthritis of the knee: the 2-year results of a randomized, double-blind, placebo-controlled clinical trial. Archives of Orthopaedic and Trauma Surgery. 2021 Oct 27:1-4.
42 Boffa A, Filardo G. Platelet-Rich Plasma for Intra-articular Injections: Preclinical and Clinical Evidence. InCartilage Tissue Engineering 2023 (pp. 381-390). Humana, New York, NY.
43 Johnson D, Dhiman N, Badhal S, Wadhwa R. Effects of Intra-articular Platelet Rich Plasma on Cartilage Thickness, Clinical and Functional Outcomes in Knee Osteoarthritis. Cureus. 2023 Jan 9;14(12).