Knee osteoarthritis is in epidemic proportions world-wide. The current population in the world is almost 8 billion. (7,965,903,063) The current estimate of the population with OA of the knee is 10% or 800,000,000. The lifetime risk of OA is 45%. Therefore, at current numbers 358,465,638 could possibly have OA of the knee. With the average life expectancy and the prevalence of obesity both increasing, the economic burden of this disease is alarming currently.
Treatment Guidelines for Knee OA
- Non -drug therapy- weight loss and exercise are primary
- Drug therapy- NSAIDS are the primary group. However, many severe side effects such as GI Bleed, Renal Disease, Liver Disease, and Heart Related Disorders
The use of drugs is restricted in people with comorbidities due to the high risk of complications.
- Intra-articular corticosteroids which provide short-term alleviation of pain and inflammation because their benefits only last a few weeks. Repeated injections have been shown to cause tissue damage and cartilage loss. Also, multiple systemic side effects such as increase of blood sugar, blood pressure and others limit the use in certain populations
- Hyaluronic Acid Injections- Pain reduction and improvement in range of motion lasting months and in some studies up to a year
- Surgery Both TKR and Arthroscopic- Arthroscopic has been proven in large studies to augment the OA in the joint over time and therefore not superior to medical therapy for certain conditions. TKR is costly and can involve operative and postoperative adverse effects.
- Biologic Therapies (Platelet Rich Plasma) PRP is autologous blood concentrate with high concentrations of platelets. These platelets liberate growth factors, cytokines and bioactive proteins that can repair cellular damage and modify an inflammatory environment leading to decreased pain and increased functionality.
Studies Demonstrating PRP Molecular Mechanism of Action
2014- Sundman reported PRP treatment in OA joint tissues resulted in diminished catabolism. PRP caused a significant decrease in matrix metalloproteinase-13. MMP-13 is the key enzyme in the cleavage of type 2 collagen and plays a pivotal role in the breakdown of cartilage in osteoarthritic joints.
This study also showed an elevation in hyaluronan synthase-2 expression in synoviocytes and an increase in cartilage synthetic activity.
This study showed that PRP stimulated Hyaluronic acid production and diminished cartilage catabolism while suppressing inflammatory mediators.
2018- Khatab- In a laboratory model, multiple PRP injections alleviated pain and synovial thickness through the modulations of macrophage subtypes. M1 activity inhibits cell proliferation and causes tissue damage while M2 activity promotes cell proliferation and tissue repair.
Consequently, PRP appears to alleviate pain and synovial inflammation by this mechanism.
2019- Liu investigated the molecular mechanism of exosomes derived from PRP involved in alleviating OA. Exosomes play critical roles in intracellular communication. This study looked at the Wnt/B-catenin pathway.
The Wnt pathway is a evolutionary pathway that regulates crucial aspects of cell fate determination, cell migration, cell polarity, neural patterning and organogenesis. This is the key effector responsible for transduction of the signal to the nucleus and it triggers transcription of specific genes responsible for the control of the cell fate decisions in cells and tissues.
Liu stated that PRP derived exosomes acting as carriers containing growth factors derived from PRP activated the Wnt/B-catenin pathway and are a novel therapy for OA treatment.
2021- Yang indicated PRP abates IL-1B induced chondrocyte apoptosis and inflammation
Sheean stated biologic activity of PRP is manifold: platelet alpha granules promote the release of various growth factors including VEGF and TGF-B and inflammation is modulated through the inhibition of the nuclear factor pathway
Uchiyama studied the concentrations of humoral factors in PRP and the impact on macrophage phenotypes. The autologous protein solution LR-PRP had a greater concentration of M1 and M2 macrophage related factors. The addition of PRP supernatants to the culture media of monocyte derived macrophages and M1 polarized macrophages showed PRP suppressed M1 macrophage polarization and promoted M2 macrophage polarization.
Tucker assessed molecular biomarkers and mesenchymal stem cells in the synovial fluid during treatment of osteoarthritic knee joints in 17 patients. Levels of growth factors were measured 10 days after treatment. Altered gene expression profiles in mesenchymal stem cells were found for metalloproteinases and inflammatory markers. Tucker postulated that PRP modulates the local knee synovial environment by modifying the inflammatory milieu, matrix degradation, and angiogenic growth factors.
Yurtbay showed multiple doses of PRP augmented the treatment efficacy and duration. Patients who received multiple injections had better and maintained higher scores at 3,6, and 12 months.
Morton clinically evaluated the effectiveness of PRP for improving functional movement in patients with OA of the knee. The outcomes of this study showed that the use of PRP injections for treating OA were shown to be successful in terms of improving functional results and diminishing pain intensity.
Hegaze studied the impact of PRP on knee OA in a prospective cohort study involving 252 patients with various grades of knee OA. The K/L system scale was used. PRP injection was administered to all patients with a maximum of 4 injections. Intra-articular injections were found to provide significant pain relief and flexion improvement in patients with Kellgren -Lawrence grades 2,3 and 4. Hegaze recommended repeated injections up to four because they appeared efficient in providing long-term alleviation of knee OA.
In another study, one, two or three PRP injections were compared. All scores were comparable at 6 weeks, 3 months and 6 months. However, at 1 year, the three injection group showed superiority is all outcomes measured and the author stated that the three dose regime is probably required to sustain the benefits seen at one year.
Baki looked at PRP for increased cartilage thickness in a 2021 study. He found a significant increase in cartilage thickness was encountered at the intercondylar area at 6 months relate to the baseline ultrasound. Treatment not only increased the thickness but relieved pain and improved knee function in the studied group.
Sanchez studied whether PRP could postpone or even avoid knee surgery in patients with knee OA. This study included 667 of whom met the inclusion criteria. Some 74.1% of the patients achieved a delay in the TKA of more than 1.5 years with a median delay of 5.3 years. The survival analysis showed 85.7% did not undergo a TKA during the 5 year follow up. The findings of this study suggested that PRP can delay TKA.
These studies and many others have demonstrated the positive effect of Platelet Rich Plasma on the structural modulation and anti-inflammatory effects on knee OA. There is definite superiority over other forms of therapy for osteoarthritis of the knee. At the very least, knee surgery can be delayed and possibly avoided altogether.
(Bibliography for the above studies can be found in the referenced articles below as they are too voluminous to mention):
Arch Orthop Trauma Surg 2021 Sept: 141(9): 1473-1490 PMID 32725315
Int J Mol Sci 2022 Feb; 23(3): 1301 PMID 35163225
Cartilage 2021 Dec; 13(1) ; 364-375S PMID 32551947
Juventix Regenerative Medical is an industry leader in the regenerative medical field. Our Platelet Rich Plasma Kits are FDA approved and designed for safety and effectiveness. They are cost effective and very easy to use. Our kits provide consistency of concentrated product when obtained from the same source.
Juventix Regenerative Medical offers a patent pending LED Photo- Activator to activate the platelets and begin the regenerative process. The activation, a critical step in the release of cytokines and growth factors, is accomplished with light and not with the addition of other chemicals such as Calcium Chloride or Thrombin.
Juventix Regenerative Medical supplies a Bio-Incubator that transforms the Platelet Rich Plasma into an Injectable Platelet Rich Fibrin. The PRF, commonly called the “second generation of platelet products, has a broader range of clinical applications while providing outstanding outcomes.
Regenerative Regards,
Dr. Robert McGrath
