Abstract
Osteoarthritis (OA) is a prevalent joint disease, particularly affecting the knees. This condition is often managed through various treatments, including intra-articular injections such as corticosteroids (CS), hyaluronic acid (HA), and platelet-rich plasma (PRP). PRP has shown promising outcomes in recent studies although it does lack strong endorsement in some clinical guidelines due to inconsistent results and lack of standardized results. This study was conducted to assess patient awareness and the frequency of PRP offered for the treatment of knee OA, compared to CS and HA. In a cross-sectional study, 46 knee OA patients were surveyed regarding their knowledge and experiences of CS, HA, and PRP injections. The questionnaires were administered between September 2022 and February 2023. Additionally, the study evaluated the severity of patients knee OA, using the Western Ontario and McMaster Universities Arthritis Index, and gathered demographic information from the participants. CS injections were offered to 93.5%, and 100% of participants had previously heard of this type of injection. HA injections were offered to 37%, and 65.9% of participants had heard of them. PRP was offered to 2%, and 6.5% had ever heard of it. This study underscores the limited awareness and utilization of PRP among knee OA patients. Patients and physicians need to be more informed of all of the treatment options available for knee OA, especially orthobiologics such as PRP. Future research in larger, diverse populations is needed.
Keywords: corticosteroid, injections, intra-articular, knee, osteoarthritis, platelet-rich plasma, PRP
Key points.
PRP is an effective treatment for knee OA in the early stages.
Patients, in some areas of the United States, are not aware that PRP is an option for knee OA. Additionally, many doctors are not offering or making patients aware of PRP, despite recent research showing its efficacy.
1. Introduction
Osteoarthritis (OA) is a degenerative joint disease that causes pain and disability in more than 10% of people over the age of 60.[1] Knee OA is the most common type of arthritis, and its prevalence continues to increase as life expectancy and obesity rises.[2] Stepwise management of knee OA usually starts with lifestyle modifications such as weight reduction, physical therapy, bracing, and walking supports accompanied by pharmacological therapy such as NSAIDs, acetaminophen as well as other oral and topical medications and supplements. Intra-articular injections (corticosteroids [CS], hyaluronic acid [HA], and platelet-rich plasma [PRP]) are used as a buffer to postpone operative management as the last line. In end stage OA, the standard treatment is joint replacement.[2]
CS can provide short term relief from knee OA symptoms.[3] HA is effective and can provide symptomatic relief, particularly in mild OA.[4,5] Additionally, regenerative medicine options, including PRP and other orthobiologics, are promising alternatives for the treatment of OA.[6] CS and HA are the more common injections provided for patients with knee OA, despite recent studies showing favorable outcomes of PRP when compared with both CS and HA injections.[7,8] These outcomes include improved pain, less joint stiffness and better participation in exercise/physical activities, including sports.[9,10] While previous research has yielded promising results, the American Academy of Orthopaedic and the American College of Rheumatology do not strongly endorse PRP therapy in their clinical guidelines. This is likely due to the observed variability in outcomes and the absence of standardized protocols for PRP preparation.[11,12]
PRP is an autologous blood product containing high levels of growth factors and platelets obtained from a small amount of blood collected through a patient peripheral vein. The blood is then concentrated by centrifugation before readministering.[13] The exact mechanism of action of PRP in the treatment of OA remains unknown; however, it is postulated that PRP stimulates chondrocytes to promote the synthesis of the cartilage matrix.[14] Growth factors, chemokines, cytokines, and other proteins in PRP are thought to decrease cartilage catabolism, pain and inflammation in the joint. The benefits of PRP for knee OA are greatest in patients with mild or moderate disease.[15] While there have been studies and data collected on the epidemiology of PRP in the treatment of orthopedic injuries, no studies have evaluated how often patients are offered or informed of PRP for the treatment of orthopedic conditions, such as knee OA. This study aimed to asses both patient awareness of PRP as a treatment option for knee OA and the frequency with which participants were offered PRP for the management of their condition.
2. Methods
2.1. Study design
This was a cross sectional study approved by the Institutional Review Board. The participants completed the questionnaires found in Supplement 1, Supplemental Digital Content 1, http://links.lww.com/MD/L282 and Supplement 2, Supplemental Digital Content 2, http://links.lww.com/MD/L283 after providing written informed consent. They were made aware that the study aimed to learn more about the specific types of injections used to treat knee OA. The questionnaires were completed under the supervision of a physician to ensure that all the questions were answered and understood. Additionally, we wanted to verify that no data was missing. Patients were surveyed on random days from September (2022) to February (2023). Our research team aimed to get at least 40 participants. This sample size was limited due to time constraints of our research team.
A traditional 5-point scale was used for the Western Ontario and McMaster Universities Arthritis Index (WOMAC) questionnaire. One point was awarded for no symptoms, and the points increased according to the increased severity of the symptoms. Five points were assigned to the most severe symptoms. Password-protected iPads were used to collect the data. Google Forms was used for the questionnaires. The data was extrapolated from the Google Form into an excel spreadsheet to create the graphs.
2.2. Participants
Participants who indicated that they had been diagnosed with knee OA were considered eligible to participate in our study, provided they met predefined criteria for inclusion. In order to confirm participants comprehended their knee condition thoroughly, we asked patients to articulate their understanding. This was done to ensure their awareness and grasp of the assessment. We did not perform additional verification of the knee OA diagnosis through radiologic studies (such as X-rays or MRIs) or chart review. The participants did not receive any compensation for their participation in the study. The eligibility criteria for inclusion were as follows:
Age ≥ 50 years
Able to understand the study protocol and questions
The exclusion criteria were:
Diagnosis of bone tumor
Diagnosis of rheumatoid arthritis
Fresh knee trauma
Patients in the waiting rooms of Garnet Health Medical Center outpatient clinics were randomly asked if they had knee OA. Patients who were diagnosed with knee OA were asked to participate in the study. All patients present in the waiting room were approached to avoid any bias in participant selection.
3. Results
The surveyed population included 16 males (34.8%) and 30 females (65.2%) for a total of 46 respondents (Table 1). The median age was 67.3 ± 7.8 with median BMI of 30.9 kg/m2 ± 5.2. The median duration of knee OA was 10.7 years. Nearly half (45.7%) reported having had a knee replacement. Additionally, we found that 38/46 (82.6%) respondents reported having had a knee injection of any sort. When asked if the respondents had ever heard of the various types of knee injections, 46/46 (100%) had heard of CS, 29/46 (63%) had heard of HA, and 5/46 (10.9%) had heard of PRP. The rates for CS, HA, and PRP were 37/46 (80.4%), 13/46 (28.3%), and 0/46 (0%) respectively. Lastly, when asked if patients had ever been offered various types of knee injections, 43/46 (93.5%) had been offered CS, 17/46 (37%) had been offered HA, and 3/46 (6.5%) had been offered PRP. The WOMAC score, the final component of the data, was collected to determine the clinical severity of the participants knee OA. The median WOMAC score was 83.5, also shown in Table 1.
Table 1.
Characteristics of the study subjects.
| Variable | Males | Females | P value |
|---|---|---|---|
| Frequency (%) | 16 (34.8) | 30 (65.2) | |
| Age (yr) | 66.3 ± 9.2 | 67.9 ± 7.1 | .554 |
| Height (in) | 70.9 ± 3.3 | 63.4 ± 2.3 | <.001 |
| Weight (lb) | 221.9 ± 33 | 178 ± 36.2 | <.001 |
| BMI (kg/m2) | 31 ± 4.6 | 30.8 ± 5.6 | .883 |
| Knee OA duration (yr) | 10.7 ± 8.2 | 10.8 ± 7.6 | .973 |
| Knee replacement? | R(1), L(1), B/L(3) | R(3), L(6), B/L(7) | |
| Knee replacement, any (%) | 5 (31.3) | 16 (53.3) | |
| Knee injected, either (%) | 13 (81.3) | 25 (83.3) | |
| Corticosteroid injection (%) | 13 (100) | 24 (96) | |
| Corticosteroid injection (%) | 37 (80.4) | ||
| HA injection (%) | 5 (38.5) | 8 (32) | |
| HA injection (%) | 13 (28.3) | ||
| PRP injection (%) | 0 (0) | 0 (0) | |
| PRP injection (%) | 0 (0) | ||
| Heard of CS? (%) | 16 (100) | 30 (100) | |
| Heard of CS? (%) | 46 (100) | ||
| Heard of HA? (%) | 9 (56.3) | 20 (66.7) | |
| Heard of HA? (%) | 29 (63) | ||
| Heard of PRP? (%) | 2 (12.5) | 3 (10) | |
| Heard of PRP? (%) | 5 (10.9) | ||
| Offered CS? (%) | 15 (93.8) | 28 (93.3) | |
| Offered CS? (%) | 43 (93.5) | ||
| Offered HA? (%) | 5 (31.3) | 12 (40) | |
| Offered HA? (%) | 17 (37) | ||
| Offered PRP? (%) | 2 (12.5) | 1 (3.3) | |
| Offered PRP? (%) | 3 (6.5) | ||
| WOMAC score | 82.8 ± 27.8 | 83.9 ± 26.6 | .896 |
| WOMAC score | 83.5 ± 26.7 | ||
BMI =body mass index, CS = corticosteroids, HA = hyaluronic acid, OA = osteoarthritis, PRP = platelet-rich plasma, WOMAC = Western Ontario and McMaster Universities Arthritis Index.
4. Discussion
The current study analyzed the awareness of patients afflicted with knee OA regarding some of the different intra-articular injection options available. Patients were surveyed to quantify how often they were offered, received or heard of 3 of the most common intra-articular injections, CS, HA, and PRP. From the survey, CS were the most popular treatment modality with regards to patient knowledge and actual intra-articular injection received. Significantly fewer patients had heard of HA injections, and a smaller portion had received them for treatment. Patients were least informed about PRP, and none of the patients surveyed had received PRP for treatment.
Of the 3 intra-articular injections mentioned above, CS are the most researched, with considerable data supporting its efficacy in temporarily reducing pain, and improving function for approximately 3 months on average.[16] As shown from the results of this study, CS are the most well known injectable treatment for knee OA and are most frequently offered to patients with this condition. CS produce anti-inflammatory and immunosuppressive effects via multiple pathways. They act by binding to the intracellular glucocorticoid receptor, affecting gene transcription, and inhibiting expression of inflammatory leukocytes, proinflammatory cytokines, and chemokines.[17] Many studies have supported the therapeutic efficacy of CS, including the 2018 Cochrane review which found CS to be more beneficial than placebo with respect to pain reduction and functional improvement.[18] However, there is growing evidence suggesting that patients given CS have proportionately greater knee cartilage loss and accelerated disease progression compared to alternate intra-articular injections. A randomized, placebo-controlled, double-blind trial in 2017 found significantly greater cartilage volume loss and no significant difference in knee pain when comparing patients receiving intra-articular triamcinolone, a type of CS, and intra-articular saline.[19]
HA is another treatment option for knee OA that is offered to patients less often than CS but more often than PRP. While 63% of the participants in this study were offered HA for the treatment of their knee OA, only 28% received the injection. It is unclear why many patients ended up declining treatment with HA. After discussion with some patients, it seemed that some did not want to return to the office for multiple rounds of injections. Additionally, others mentioned issues with insurance coverage for this treatment modality.
HA is a naturally occurring substance in the body and a common component of the articular cartilage and synovial fluid. It is a non-protein glycosaminoglycan that is partially responsible for the viscoelasticity and lubrication of the synovial fluid. With disease progression of OA, the viscoelastic and lubricative properties of HA decrease as the concentration of HA and the average distribution of HA molecular weight decreases. Most studies suggest that HA can reduce chondrocyte apoptosis and increase chondrocyte proliferation.[20]
In a 2018 review that analyzed multiple RCTs and meta-analyses Maheu et al reported the efficacy and safety of HA injections.[21] While there are many other studies that share the same conclusion there are also studies that report no difference in efficacy such as an RCT that studied HA injections in 251 patients versus saline placebo showing no significant pain reduction.[22] A more recent RCT conducted in 2022 randomly assigned 75 patients to treatment groups of PRP, HA, and CS and found that PRP showed a significantly greater decrease of mean WOMAC score when compared with CS and HA. Comparison of mean pain score showed that although CS improved pain greatly in the first 1.5 months, PRP followed by HA had greater long-term benefits compared to CS in the pain WOMAC subscale at 3 and 6 months.[23]
Since joint arthroplasties have a limited lifespan and are not free of complications, there is a strong need for disease-modifying drugs or therapies in the early stages. PRP is an orthobiologic therapy that has emerged in recent years. PRP is an autologous blood product with a high platelet concentration. These platelets contain growth factors which recruit and activate other immune cells.[24] Initially used to accelerate wound healing in maxillofacial surgery, PRP utility has expanded to anti-aging treatments, vitiligo, and even post-surgical healing.[25] Many mechanisms have been proposed over the last 10 years, describing the biological action of PRP in the treatment of OA. Sundman et al found that PRP treatment resulted in a significant increase in cartilage synthetic activity. The findings of this study support the idea that PRP stimulates endogenous HA production and suppresses inflammatory mediator concentrations.[26]
Several randomized controlled trials have evaluated PRP in the treatment of knee OA. However, there have been no studies evaluating the frequency at which patients were made aware of or offered PRP as a treatment for knee OA. The results of this study indicate that many patients with knee OA are unaware that PRP is a treatment option for knee OA. This study did not determine why patients are less aware of PRP, which is likely to be multifactorial. PRP has emerged more recently than CS and HA for the treatment of OA. Therefore, there is a lack of consistent, multicenter, randomized control trials evaluating PRP in different levels of OA.
Current management guidelines from the American Academy of Orthopaedic Surgeons recently downgraded its recommendation from strong to limited, mainly due to heterogenous evidence.[11] There is also a wide variation in the application and administration of PRP among physicians.[27] Additionally, PRP is not covered by insurance plans, while CS and HA often do not require out-of-pocket expenses. The typical expenses associated with PRP treatment amount to approximately $1000, which could be attributed to the expenses related to commercially accessible PRP kits and the requirement for the participation of extra medical personnel.[27]
While CS injections remain the most common injection for knee OA, several studies have shown superior outcomes with PRP when compared with both CS and HA injections. Donovan et al evaluated 10 different randomized controlled trials in which they found that repeated intra-articular CS injections improved pain, function and stiffness from 3 months to 23 months, and the alternative injectables such as HA and PRP often demonstrated an equal or more beneficial effect.[28] In a more recent review conducted in 2023, Belk et al assessed 21 different studies with level 1 evidence and compared clinical efficacy of PRP with HA treatments in patients with knee OA.[29] This review utilized patient recorded outcomes, such as visual analog pain scale and WOMAC index. The results showed none of the HA clinical outcomes were superior to PRP, while 15 out of the 29 possible outcomes resulted in greater improvement with PRP. No significant adverse side effects of PRP were noted in any of these studies. It should be mentioned that the administration methodology and concentration of PRP was heterogenous across the studies used in the reviews.
While there have been many studies showing the efficacy of PRP in the treatment of knee OA, other, newer studies have evaluated PRP contents to determine the most effective platelet concentration. Additionally, studies have shown the benefits of intraosseous PRP injections in the treatment of knee OA. Interosseous PRP injections aim to have a therapeutic effect on subchondral bone, where the pathogenesis of OA is thought to begin. Although these injections are relatively novel, there is hope that interosseous injections could slow the progression of OA by targeting subchondral bone.[30] PRP has been proven to work in many different capacities and more studies are needed to determine the most optimal dose and location when treating knee OA.
5. Limitations
One limitation of this study was the failure of blinded subjects. We assisted patients in filling out the questionnaire to ensure that they answered all questions and responded appropriately. Therefore, patients may have altered their responses due to the Hawthorne effect.
Additionally, the results of this study are not generalizable given the study population. The participants in our study were only people from Orange County, New York and the surrounding areas. While doctors in this geographical location do not frequently offer PRP as a treatment option for knee OA, it is possible that PRP is more often offered in other cities and states. This study also featured a relatively small sample size, which restricts its potential for broad applicability.
6. Conclusion
As a result of this study, it appears there is a need for more effort among medical educators and physicians to inform the general population of all relevant treatment options available for knee OA. Many orthopedic surgeons, physiatrists, rheumatologists, primary care physicians, sports medicine physicians, and other OA treatment providers do not offer PRP as a treatment option. Therefore, both at the local and national levels, physicians need to be aware of the various treatment options for knee OA, especially PRP injections. Future studies are needed to evaluate the frequency of PRP injections offered and performed in a larger population from a more expansive geographical area.
Author contributions
Conceptualization: Joel Klein, Eleonora Feketeova.
Data curation: Joel Klein, Chirag Soni, Brian Ayotte, Eleonora Feketeova.
Formal analysis: Joel Klein, Eleonora Feketeova.
Project administration: Joel Klein.
Supervision: Joel Klein, Cristian Castro-Nunez, Eleonora Feketeova.
Writing – original draft: Joel Klein, Chirag Soni, Brian Ayotte.
Writing – review & editing: Joel Klein, Chirag Soni, Eleonora Feketeova.
Supplementary Material
Abbreviations:
- CS
- corticosteroids
- HA
- hyaluronic acid
- OA
- osteoarthritis
- PRP
- platelet-rich plasma
- WOMAC
- Western Ontario and McMaster Universities Arthritis Index
Data sharing not applicable to this article as no datasets were generated or analyzed during the current study.
Supplemental Digital Content is available for this article.
The authors have no funding and conflicts of interest to disclose.
This work was carried out under research program at Garnet Health Medical Center.
How to cite this article: Klein J, Soni C, Ayotte B, Castro-Nunez C, Feketeova E. Are patients with knee osteoarthritis aware that platelet-rich plasma is a treatment option?. Medicine 2023;103:3(e36712).
Contributor Information
Chirag Soni, Email: csoni@student.touro.edu.
Brian Ayotte, Email: ayotte61@gmail.com.
Cristian Castro-Nunez, Email: ccastro1@garnethealth.org.
Eleonora Feketeova, Email: efeketeova@garnethealth.org.
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