Orthobiologics in Knee Osteoarthritis: A Review of Evidence

Osteoarthritis (OA) of the knee is a progressive degenerative joint disease that leads to pain, disability, and decreased quality of life. Traditional treatments such as pharmacological interventions, physical therapy, and surgical procedures (e.g., joint replacement) are commonly employed to manage symptoms. However, there has been increasing interest in the use of orthobiologics, a category of biologic therapies that aim to enhance the body's healing response, in treating knee OA. These treatments often include platelet-rich plasma (PRP), mesenchymal stem cells (MSCs), hyaluronic acid (HA), and other biologic agents.

Traditional methods for managing knee OA, such as physical therapy, medications, and knee replacement surgery, offer varying levels of relief. Knee replacement, in particular, is highly effective for severe OA but requires invasive surgery, a long recovery period, and carries risks like infection or prosthesis failure. In contrast, orthobiologic treatments, including platelet-rich plasma (PRP) and cell therapy, are minimally invasive options that aim to promote healing and cartilage regeneration. While they may provide relief and delay the need for surgery, their effectiveness is still debated, particularly in advanced cases, and results can vary. Overall, traditional methods, especially surgery, offer more definitive solutions but come with higher risks and longer recovery times, whereas orthobiologics are promising but better suited for early to moderate OA.

This review will summarise the evidence supporting the use of orthobiologics in the management of knee osteoarthritis, evaluating their mechanisms of action, efficacy, safety, and potential roles in clinical practice.

1. Platelet-Rich Plasma (PRP)

Mechanism of Action:

PRP is derived from the patient's own blood and contains a higher concentration of platelets, which release growth factors and cytokines that promote tissue healing, reduce inflammation, and modulate pain.

Efficacy:

Numerous studies have demonstrated that PRP can provide significant improvement in pain and function in knee OA patients. A systematic review and meta-analysis published in The American Journal of Sports Medicine (2017) found that PRP injections were superior to placebo and hyaluronic acid in improving pain and function, particularly in the short-to-medium term.

- Pros: PRP has been shown to reduce inflammation, promote cartilage regeneration, and improve joint function.

- Cons: The variability in PRP preparation protocols and lack of standardised clinical application limit its universal recommendation.

Safety:

PRP is generally considered safe due to its autologous nature, which reduces the risk of immune rejection or disease transmission. However, there can be mild adverse events such as pain at the injection site.

2. Mesenchymal Stem Cells (MSCs)

Mechanism of Action:

MSCs are pluripotent cells that have the potential to differentiate into chondrocytes (cartilage cells) and secrete bioactive molecules that promote tissue regeneration and reduce inflammation. They can be sourced from bone marrow, adipose tissue, or synovium.

Efficacy:

The evidence on MSCs for knee OA is promising but still inconclusive. Several clinical trials have reported improvements in pain, function, and cartilage regeneration. A randomised controlled trial? published in The Lancet (2020) showed that MSC injections could lead to improved outcomes compared to placebo, with some evidence of cartilage repair.

- Pros: MSCs have the potential for long-term benefits by promoting cartilage repair and reducing inflammation.

- Cons: The clinical application is limited by the availability of standardized protocols and variability in cell sources.

Safety:

MSCs are considered safe with low incidence of serious adverse events.

?3. Hyaluronic Acid (HA)

Mechanism of Action:

HA is a naturally occurring substance in the joint synovial fluid, providing lubrication and reducing friction. In OA, the concentration of HA decreases, leading to joint stiffness and pain. Exogenous HA injections are used to restore joint viscosity and improve mobility.

Efficacy:

HA injections have been widely studied for knee OA. Numerous studies have shown moderate improvements in pain and function, especially in mild to moderate OA. A meta-analysis published in Osteoarthritis and Cartilage (2016) concluded that HA is effective in reducing pain and improving function for up to 6 months after treatment, though results can be variable depending on the type of HA used.

- Pros: HA is well-studied, widely available, and has a relatively favorable safety profile.

- Cons: The effect of HA injections tends to be temporary, and the response can vary between patients. Some studies show limited benefits in advanced OA.

Safety:

HA is generally considered safe, with minor side effects like transient swelling or pain at the injection site. There is no significant risk of serious adverse effects, making it a low-risk treatment option.

4. Other Orthobiologic Treatments

Other orthobiologic therapies, such as autologous conditioned serum (ACS) and growth factors like transforming growth factor-beta (TGF-β) and insulin-like growth factor (IGF-1), have been explored as potential treatments for knee OA.

-Autologous Conditioned Serum (ACS): Derived from blood, ACS contains anti-inflammatory cytokines and growth factors. Preliminary studies suggest it can improve pain and function, but more high-quality trials are needed.

- Growth Factor Injections: Various growth factors have been explored for cartilage regeneration and pain relief, with early-phase studies showing mixed results.

Challenges and Future Directions

- Lack of Standardization: One of the major limitations of orthobiologic therapies is the lack of standardization in preparation techniques, dosing, and protocols. This variability makes it difficult to compare results across studies and could impact clinical outcomes.

-Long-term Efficacy: While short- to medium-term results are promising, the long-term benefits of these therapies, particularly MSCs and PRP, are not fully understood. Long-term, well-designed trials are needed.

- Personalised Medicine: The variability in patient response suggests that orthobiologic treatments may benefit from personalized approaches, considering factors such as disease stage, cellular composition, and genetic predispositions.

?Conclusion

Orthobiologics represent a promising frontier in the management of knee osteoarthritis. While evidence supports the use of PRP, MSCs, and HA in improving pain and function, the clinical effectiveness varies, and long-term benefits remain uncertain. Further research is needed to optimise treatment protocols, understand long-term outcomes, and establish clear guidelines for clinical practice. However, as part of a comprehensive treatment approach, orthobiologics may offer valuable alternatives or adjuncts to traditional therapies for patients with knee OA.

?References?

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