Osteoarthritis (OA) is a degenerative joint disorder characterized by the progressive erosion of articular cartilage, accompanied by subchondral bone remodeling, osteophyte formation, and synovial inflammation. In the context of the knee, OA presents a particular challenge given the knee’s pivotal role in ambulation and weight-bearing activities. The pathogenesis of knee OA encompasses biomechanical forces, genetic predispositions, systemic inflammatory mediators, and local biochemical changes. Over time, this leads to joint space narrowing, pain, stiffness, and often culminates in functional disability.

Platelet-Rich Plasma (PRP) is an autologous blood product with a platelet concentration above the baseline of whole blood. PRP is obtained through centrifugation, which segregates the platelet-poor plasma, red blood cells, and PRP based on their respective densities. PRP’s therapeutic potential stems from its rich reservoir of growth factors and cytokines, such as platelet-derived growth factor (PDGF), transforming growth factor-beta (TGF-β), and vascular endothelial growth factor (VEGF), among others.

In the realm of orthopedics, PRP is posited to modulate the inflammatory response, enhance tissue repair mechanisms, and stimulate chondrocyte differentiation and proliferation. For knee OA, the intra-articular injection of PRP aims to reduce pain, improve joint function, and possibly decelerate the degenerative process by harnessing these bioactive molecules.

Given the increasing prevalence of knee OA and its substantial impact on healthcare systems and patient quality of life, the exploration of innovative treatment modalities like PRP is imperative. As an autologous treatment, PRP presents a favorable safety profile, mitigating concerns of immunogenicity or transmission of blood-borne pathogens. However, potential risks, such as infection, pain at the injection site, or disease exacerbation, should not be overlooked.

Evaluating PRP’s efficacy is equally crucial. While initial studies and clinical trials have showcased promising results, the lack of standardized PRP preparation protocols, heterogeneity in study designs, and variability in outcome measures underscore the need for rigorous, large-scale randomized controlled trials. A comprehensive understanding of PRP’s safety and efficacy is paramount for integrating it into evidence-based practice, guiding patient-centered care, and optimizing therapeutic outcomes for knee OA.

Background on PRP

What is PRP?

What is PRP?

Extraction and preparation process

Platelet-Rich Plasma (PRP) is an autologous concentration of platelets in a small volume of plasma. The extraction process begins with venipuncture, where a sample of the patient’s blood is drawn. This blood is then subjected to centrifugation, typically in a two-step process:

  • The “first spin”, or “soft spin,” separates the blood into three layers: platelet-poor plasma (PPP) at the top, PRP in the middle, and red blood cells (RBCs) at the bottom.
  • A “second spin”, or “hard spin,” is then performed on the PRP layer to concentrate the platelets further. Post this spin, the supernatant is discarded, leaving behind the highly concentrated platelets in a small volume of plasma.

The final PRP product can vary based on the centrifugation protocols, kits used, and specific requirements of the procedure, leading to classifications like leukocyte-rich PRP (LR-PRP) and leukocyte-poor PRP (LP-PRP) based on leukocyte concentration.

Constituents of PRP and their purported healing properties

The therapeutic efficacy of PRP is largely attributed to its rich milieu of bioactive substances:

Growth Factors”: These are proteins that play pivotal roles in cell proliferation, differentiation, and angiogenesis. Vascular endothelial growth factor (VEGF), transforming growth factor-beta (TGF-β), platelet-derived growth factor (PDGF), and epidermal growth factor (EGF) are among the many growth factors that are abundant in PRP. These factors can accelerate tissue healing, modulate inflammation, and promote cellular migration.

Cytokines”: These are small proteins that mediate and regulate immunity, inflammation, and hematopoiesis. Some of the key cytokines in PRP include interleukins (like IL-4, IL-13), which have roles in modulating immune responses and can impact tissue repair processes.

Fibrin Matrix”: This is a protein structure crucial for clot formation, and in the context of PRP, it serves as a scaffold that can support cellular migration and tissue regeneration.

Historical and current uses of PRP in medical treatments

Historically, PRP’s introduction into the medical domain was marked by its use in the 1970s for the treatment of large bone defects in maxillofacial surgery. It later gained traction in the 1980s within the field of cardiac surgery to minimize transfusions. By the 1990s and early 2000s, its application expanded to orthopedic and sports medicine due to its potential in promoting wound healing and tissue regeneration.

Today, PRP has a myriad of applications:

  • Orthopedics: Used in conditions such as tendinopathies, ligament injuries, and osteoarthritis, particularly in the knee.
  • Sports Medicine: Athletes with acute injuries or chronic wear-and-tear conditions have turned to PRP to potentially expedite the healing process and reduce downtime.
  • Dermatology and Aesthetic Medicine: Known as the “vampire facial,” PRP is used for skin rejuvenation, reducing wrinkles, and treating alopecia.
  • Oral and Maxillofacial Surgery: Utilized for bone grafting procedures, dental implants, and in the treatment of certain oral ulcers.
  • Ophthalmology: Explored in the treatment of ocular surface disorders and corneal epithelial defects.

In essence, the appeal of PRP stems from its potential to harness the body’s own healing mechanisms, reduce recovery times, and possibly provide an alternative to more invasive interventions or surgeries.

Mechanism of PRP in Treating Knee OA

Mechanism of PRP in Treating Knee OA

The theory behind PRP’s regenerative capabilities

The foundational premise of PRP’s regenerative prowess centers around the concept of harnessing the body’s intrinsic healing mechanisms. Platelets are primarily recognized for their hemostatic functions but are also reservoirs of a multitude of bioactive substances, including growth factors, cytokines, and chemokines. When introduced into damaged or degenerative tissues, these substances can potentially modulate cellular activities, promote tissue regeneration, and dampen inflammation, all of which are pivotal in counteracting the pathological processes underlying knee OA.

Interaction between platelets and damaged joint tissues

Upon intra-articular injection of PRP, platelets come into contact with the damaged joint environment, characterized by exposed collagen and other matrix components. This contact, in conjunction with the physiological processes of platelet activation (e.g., by thrombin or collagen), leads to degranulation of the alpha and dense granules within the platelets. As a result, a cascade of bioactive molecules is released directly into the synovial milieu.

Moreover, PRP’s interaction with the damaged joint milieu also impacts synoviocytes, chondrocytes, and other resident cells. These cells, when exposed to PRP, may exhibit altered phenotypes, enhanced proliferation rates, and augmented matrix synthesis. Additionally, the presence of certain cytokines in PRP can influence macrophage polarization, potentially skewing them towards a pro-resolving, anti-inflammatory M2 phenotype, which is beneficial in the context of OA’s chronic inflammatory state.

Role of growth factors released from platelets

Growth factors, a cornerstone of PRP’s therapeutic potential, have multifaceted roles in joint health and disease modulation:

Platelet-Derived Growth Factor (PDGF): Recognized for its mitogenic properties, PDGF promotes the proliferation of synovial fibroblasts and chondrocytes. It also plays a role in angiogenesis, which, though contentious in OA, might be essential during the early phases of tissue repair.

Transforming Growth Factor-beta (TGF-β): Crucial in cartilage homeostasis, TGF-β stimulates matrix synthesis and inhibits matrix degradation by downregulating proteolytic enzymes such as matrix metalloproteinases (MMPs). Additionally, it has chondrogenic properties, promoting differentiation of mesenchymal stem cells into chondrocytes.

Vascular Endothelial Growth Factor (VEGF): While primarily associated with angiogenesis, in the joint environment, VEGF might also influence synovial proliferation and joint inflammation.

Insulin-like Growth Factor-1 (IGF-1): This growth factor supports chondrocyte metabolism, promoting matrix synthesis and potentially attenuating chondrocyte apoptosis.

The orchestration of these growth factors, in synergy with other bioactive molecules, is believed to create an environment conducive to tissue repair, inflammation resolution, and potentially, some degree of joint regeneration.

Clinical Evidence on the Efficacy of PRP

Overview of major clinical trials and studies

The use of PRP in osteoarthritis (OA) management has been the subject of multiple clinical trials and observational studies. Many have aimed to ascertain its safety and efficacy profile, particularly regarding pain management and functional improvement. A notable meta-analysis conducted by [Laudy et al., 2015] reviewed 10 randomized controlled trials and demonstrated that PRP injections reduced pain more effectively than hyaluronic acid injections and placebo in OA patients (1).

Positive outcomes and success stories

Several studies reported positive outcomes post-PRP treatment. For instance, a randomized controlled trial by [Patel et al., 2013] found that PRP therapy resulted in significant reductions in pain and stiffness while improving the physical function of the knee compared to placebo controls (2). Another study by [Cerza et al., 2012] showed that PRP treatment led to better and more lasting improvements in symptoms than hyaluronic acid injections (3).

Cases with minimal or no improvement

While many patients have benefitted from PRP treatments, not all experienced positive results. Some trials have documented a subset of patients who showed minimal or no improvement post-treatment, underscoring the variability in individual responses and PRP preparation methods might contribute to these variable outcomes (4).

Comparison with other treatment modalities (e.g., hyaluronic acid injections, corticosteroids)

When comparing PRP with other intra-articular injections, particularly hyaluronic acid and corticosteroids:

  • PRP was found to provide better and longer-lasting pain relief and functional improvement than hyaluronic acid (5).
  • Corticosteroids provide quicker pain relief, but their effects are often short-lived and can have detrimental effects on cartilage with repeated use. In contrast, PRP aims to harness regenerative properties to provide more sustained benefits (6).

Duration of pain relief and need for repeated injections

The relief from pain post-PRP treatment varies among individuals. However, studies like that by [Görmeli et al., 2017] indicated that its benefits could last up to 12 months or longer. Some patients might require repeated injections, depending on their response and the progression of OA (7). The optimal frequency and number of injections remain topics of ongoing research.

Safety Profile of PRP

Potential side effects and complications

The use of autologous PRP, by virtue of being derived from a patient’s own blood, inherently minimizes the risks associated with foreign substance reactions. However, like all therapeutic interventions, PRP is not entirely devoid of potential side effects:

Injection site reactions: These can range from mild pain, swelling, redness, or warmth at the injection site, which typically resolve within a few days (8). Rarely, more severe reactions, like excessive inflammation or joint effusion, might be encountered.

Infection: As with any invasive procedure, there’s always a risk of introducing pathogens. Proper aseptic technique is paramount to minimize this risk.

Tissue damage or injury: Caution is required to avoid damage to the surrounding tissues, tendons, ligaments, or nerves during the injection.

Calcification at the injection site: There have been sporadic reports of soft tissue calcification following PRP treatment, though the exact pathophysiology remains unclear.

Relative risk compared to other treatments

When juxtaposing PRP with other commonly employed intra-articular treatments, its safety profile is comparably favorable:

Hyaluronic Acid (HA): Both PRP and HA share a similar side effect profile, with post-injection pain and swelling being the most common. However, PRP lacks the avian-derived proteins found in some HA products, mitigating the risk of allergic reactions (Belk et al., 2018).

Corticosteroids: While steroids offer rapid relief, their repeated use can accelerate joint degeneration, potentially exacerbate cartilage loss, and elevate the risk of joint infection. Systemic effects like transient elevation of blood sugars in diabetics are also noted. In comparison, PRP does not have these deleterious effects on joint cartilage and lacks the systemic side effects inherent to steroids.

Patient variables that might influence side effects (e.g., age, severity of OA)

Individual patient characteristics can play a role in both the efficacy and safety of PRP:

Age: Older patients, especially those with co-morbid conditions, might have a heightened risk of post-injection complications. Additionally, the platelet function and concentration of growth factors might vary with age, potentially influencing the therapeutic outcome (10).

Severity of OA: Patients with advanced OA may experience less pronounced benefits and a slightly higher risk of post-injection pain or effusion. This might be attributable to the already compromised joint environment. Although it can still be effective in pain management and improving joint function (70)

Underlying Health Conditions: Conditions like diabetes, autoimmune diseases, or chronic inflammatory states can influence tissue healing and response to treatments, including PRP.

Medications and Supplements: Some drugs, especially non-steroidal anti-inflammatory drugs (NSAIDs), might affect platelet function. Prior use of these medications might modulate the efficacy and side effect profile of PRP.

Best Treatment Technique for Knee OA

Structural Diagnosis and Management (SDM) is a specialized manual technique in physiotherapy that stands out as one of the best for addressing knee osteoarthritis (OA). This advanced approach combines several key elements to promote healing and restore function. It incorporates manipulation to adjust the joint structures, ensuring they are aligned correctly. Techniques like muscle press pull are applied to rectify muscle imbalances. Simultaneously, muscle activation and stretching exercises help improve flexibility and range of motion, ensuring muscles support the joint adequately. Strengthening exercises are employed to fortify muscles around the knee, reducing strain on the joint. Furthermore, joint mobilization techniques ensure that the knee joint remains fluid and can move without pain or restriction. So why should a patient choose this treatment? Well, at Agrani Specialized Manipulation Therapy Centre, experts are trained in the SDM technique, ensuring that patients receive targeted, personalized care. By opting for this therapy, patients are choosing a comprehensive approach that aims to tackle the root causes of their discomfort, rather than just alleviating symptoms. This ensures a holistic healing process, promoting long-term joint health and overall well-being.

Conclusion

PRP is generally seen as a safe option for treating knee OA. Since it’s derived from a person’s own blood, the chances of having an allergic reaction or infection are relatively low. However, that doesn’t mean it’s entirely without side effects. Some people might experience temporary discomfort, like swelling or pain, where they received the injection. In terms of its effectiveness, the results are promising but mixed. While many have found relief and improved knee function, others haven’t noticed much of a change.

For those considering PRP as a treatment option, it’s crucial to do your homework. Find a reputable doctor to discuss if PRP is the right fit based on your health and specific situation. It’s also a good idea to set realistic expectations. While PRP can provide relief, it’s not a magic cure for everyone. Also, keep in mind the cost factor. PRP treatments can be pricey, and many insurance companies might not cover it, viewing it as more experimental.

Looking ahead, the interest in PRP is only expected to grow. As more people seek out less invasive alternatives to surgery, treatments like PRP will likely become more mainstream. Research is ongoing, with scientists and doctors continually exploring ways to enhance its effectiveness. This might include combining PRP with other therapies or fine-tuning the preparation process. And while our focus has been on knee OA, there’s a lot of curiosity about how PRP might benefit other joints or injuries.

FAQ’s

Q1: What exactly is PRP, and how is it used for knee osteoarthritis?

A: PRP stands for Platelet-Rich Plasma. It is a treatment where a patient’s blood is drawn, processed, and then injected into the affected joint. The idea is that the growth factors in PRP can promote healing and reduce inflammation in the knee, providing relief from osteoarthritis symptoms.

Q2: How long does it take to see results after a PRP injection?

A: It varies from patient to patient. Some may feel improvement within a few weeks, while others might require a couple of months. It’s essential to note that multiple treatments might be necessary for optimal results.

Q3: Are there any side effects associated with PRP injections for knee OA?

A: Some common side effects include pain or discomfort at the injection site, swelling, and temporary redness or warmth. However, because PRP is derived from a patient’s blood, the risk of allergic reactions or transmission of infections is minimized.

Q4: How does PRP compare to other treatments like hyaluronic acid injections or corticosteroids?

A: PRP offers a natural approach, utilizing the body’s healing mechanisms. Some studies suggest PRP may provide longer-lasting relief compared to corticosteroids. Hyaluronic acid injections provide lubrication to the joint, while PRP focuses on healing and reducing inflammation. The best treatment often depends on individual patient needs and the severity of the condition.

Q5: Is PRP treatment covered by insurance?

A: Coverage varies among providers. While PRP has gained popularity, not all insurance companies recognize it as a standard treatment. It’s crucial to consult with your insurance provider to determine coverage specifics.

Q6: How many PRP injections are typically required for knee osteoarthritis?

A: The number of injections varies based on the patient’s condition and response to treatment. Some may benefit from a single injection, while others might need a series of injections spaced several weeks apart.

Q7: Is there any post-treatment care required after receiving a PRP injection?

A: It’s typically advised to rest the treated area for a few days following the injection. Applying ice can help reduce any swelling or discomfort. It’s also essential to follow any specific recommendations or physical therapy exercises provided by the healthcare practitioner.

Q8: Can anyone with knee osteoarthritis get PRP treatment?

A: While many patients with knee OA can benefit from PRP, it’s crucial to consult with a healthcare professional to determine if it’s the right treatment option based on individual circumstances and the disease’s progression.

References

1. Laudy, A.B., Bakker, E.W., Rekers, M. and Moen, M.H., 2015. Efficacy of platelet-rich plasma injections in osteoarthritis of the knee: a systematic review and meta-analysis. British journal of sports medicine, 49(10), pp.657-672.https://bjsm.bmj.com/content/49/10/657.short

2. Patel, S., Dhillon, M.S., Aggarwal, S., Marwaha, N. and Jain, A., 2013. Treatment with platelet-rich plasma is more effective than placebo for knee osteoarthritis: a prospective, double-blind, randomized trial. The American journal of sports medicine, 41(2), pp.356-364.
https://journals.sagepub.com/doi/abs/10.1177/0363546512471299

3. Cerza, F., Carnì, S., Carcangiu, A., Di Vavo, I., Schiavilla, V., Pecora, A., De Biasi, G. and Ciuffreda, M., 2012. Comparison between hyaluronic acid and platelet-rich plasma, intra-articular infiltration in the treatment of gonarthrosis. The American journal of sports medicine, 40(12), pp.2822-2827.
https://journals.sagepub.com/doi/abs/10.1177/0363546512461902

4. Filardo, G., Kon, E., Di Martino, A., Di Matteo, B., Merli, M.L., Cenacchi, A., Fornasari, P.M. and Marcacci, M., 2012. Platelet-rich plasma vs hyaluronic acid to treat knee degenerative pathology: study design and preliminary results of a randomized controlled trial. BMC musculoskeletal disorders, 13(1), pp.1-8.
https://bmcmusculoskeletdisord.biomedcentral.com/articles/10.1186/1471-2474-13-229

5. Sánchez, M., Anitua, E., Azofra, J., Aguirre, J.J. and Andia, I., 2008. Intra-articular injection of an autologous preparation rich in growth factors for the treatment of knee OA: a retrospective cohort study. Clin Exp Rheumatol, 26(5), pp.910-913.
https://www.clinexprheumatol.org/article.asp?a=3505

6. Duymus, T.M., Mutlu, S., Dernek, B., Komur, B., Aydogmus, S. and Kesiktas, F.N., 2017. Choice of intra-articular injection in treatment of knee osteoarthritis: platelet-rich plasma, hyaluronic acid or ozone options. Knee surgery, sports traumatology, arthroscopy, 25, pp.485-492.
https://link.springer.com/article/10.1007/s00167-016-4110-5

7. Görmeli, G., Görmeli, C.A., Ataoglu, B., Çolak, C., Aslantürk, O. and Ertem, K., 2017. Multiple PRP injections are more effective than single injections and hyaluronic acid in knees with early osteoarthritis: a randomized, double-blind, placebo-controlled trial. Knee Surgery, Sports Traumatology, Arthroscopy, 25(3), pp.958-965.
https://link.springer.com/article/10.1007/s00167-015-3705-6?platform=hootsuite

8. Meheux, C.J., McCulloch, P.C., Lintner, D.M., Varner, K.E. and Harris, J.D., 2016. Efficacy of intra-articular platelet-rich plasma injections in knee osteoarthritis: a systematic review. Arthroscopy: The Journal of Arthroscopic & Related Surgery, 32(3), pp.495-505.
https://www.sciencedirect.com/science/article/pii/S0749806315006593

9. Belk, J.W., Kraeutler, M.J., Houck, D.A., Goodrich, J.A., Dragoo, J.L. and McCarty, E.C., 2021. Platelet-rich plasma versus hyaluronic acid for knee osteoarthritis: a systematic review and meta-analysis of randomized controlled trials. The American journal of sports medicine, 49(1), pp.249-260.
https://journals.sagepub.com/doi/abs/10.1177/0363546520909397

10. Eppley, B.L., Woodell, J.E. and Higgins, J., 2004. Platelet quantification and growth factor analysis from platelet-rich plasma: implications for wound healing. Plastic and reconstructive surgery, 114(6), pp.1502-1508.
https://journals.lww.com/plasreconsurg/Fulltext/2004/11000/Nevoid_Hyperkeratosis_of_the_Areola.19.aspx

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