Corticosteroids are the most frequently prescribed injection for treating arthrofibrosis (see below). Injections into a joint (intraarticular) are associated with some risks, including infection and bleeding, and although the risk is small, it does exist. Also, the needle itself causes a small amount of cell death and trauma. Some injections are subcutaneous (into the skin) and are not placed into the affected joint.
Morris et. al.  present an exciting possibility for reducing arthrofibrosis risk after TKR surgery, using a rat model of knee replacement. A mix of adenosine, lidocaine and Mg2+ (ALM) injected into the joint immediately after closure of the capsule significantly reduced fibrosis, increased range of motion and reduced fibrotic and inflammatory markers.
There are pros and cons to having a cortisone (corticosteroid) injection
There are pros and cons to having a cortisone (corticosteroid) injection and it’s not clear if the positives outweigh the negatives for treating arthrofibrosis . Injected corticosteroids are placed into a joint and are associated with a higher risk of infection, especially where there is a prosthesis. Repeated injections are known to damage cartilage  and tendons .
Pros: corticosteroids help to reduce inflammation in the short term. Most types last about 6 days, and this might help to settle arthrofibrosis.
Cons: Recent research suggests that anti-inflammatories should not be given immediately after surgery . In addition, it’s known that corticosteroids are toxic to cartilage, at least at higher doses and when repeated, and have negative impacts on bone .
Questions to ask are:
What dose will be used? This is really important because the evidence suggests that low doses of injected corticosteroids may be beneficial, at least if they are not repeated often. Studies suggest that higher doses – often the recommended dose – are toxic to cartilage cells and are more likely to cause cartilage damage.
What type of corticosteroid will be used? There are a number of types that have slightly differing actions. All can be toxic to cartilage at higher doses.
Different inflammatory cytokines are targeted by specific biologics
For some people with arthrofibrosis monoclonal antibodies or receptor antagonists targeted at specific pro-inflammatory cytokines help to reduce pain and increase mobility. Different inflammatory cytokines are targeted by specific biologics, and a cytokine blood test can determine which treatment may be effective. Biologics are usually injected. Biologics do not typically have off-target side-effects like other medications do, but because they downregulate the immune system there is an increased risk of infection.
Simponi / Humira
Simponi and Humira require regular subcutaneous injections that can be done at home with a pre-loaded “auto-inject” pen. These medications and others like them target a key pro-inflammatory cytokine called TNF-α. The different brands are slightly different in their specific binding and one brand may work better than another for any particular individual.
Anakinra is beginning to be prescribed off-label by some surgeons post operatively. This biologic is an IL-1 antagonist – that is, it blocks the ability of the inflammatory cytokine IL-1 to signal to cells, and therefore prevents tissue damage caused by excessive inflammation . Anakinra has shown some efficacy for treating arthrofibrosis in small trials, however typically only one or two injections are given. Due to the short duration of action, daily subcutaneous injections of Anakinra might be more helpful  in cases where IL-1 is elevated in blood tests.
A mix of adenosine, lidocaine and Mg2+
Morris et. al.  present an exciting possibility for reducing arthrofibrosis risk after TKR surgery, using a rat model of knee replacement. A mix of adenosine, lidocaine and Mg2+ (ALM) injected into the joint immediately after closure of the capsule significantly reduced fibrosis, increased range of motion and reduced fibrotic and inflammatory markers. ALM appears to be an effective preventative, at least in heathy joints. 24 healthy male rats had one knee replaced with a custom titanium prosthesis, under anaesthesia. The rats were given an injection into the joint at the end of surgery. Half received ALM, and half had saline injected (the control group) after closure of the capsule. At 4 weeks post-surgery the knees of ALM treated rats had twice the range of motion compared to the control group knees. ALM knees had significantly decreased synovitis and fibrotic pathology in the joint capsule and Infrapatellar fat pad compared to saline controls. In addition the protein and RNA levels of the major pro-fibrotic and inflammatory mediators were significantly lower in the ALM treated animals.
Please note that this experiment was conducted in healthy animals. Humans with osteoarthritis, fibrosis or other inflammatory conditions may react differently. However, further research indicates that the mix of adenosine, lidocaine and Mg2+ may significantly reduce the major stressors that an operation induces, and therefore reduce the risk of fibrosis.
This study used “blinded” investigators – that is, the surgeons and those that evaluated the outcomes (for example, fibrotic changes) didn’t know which individuals received the treatment, and which were controls. This method is used in good quality research to eliminate or reduce the possibility of bias in the results.
Pentosan Polysulphate Sodium (PPS) Injection
Phase 3 clinical trials for treating knee osteoarthritis (OA) will use twice weekly subcutaneous injections of pentosan polysulphate sodium (PPS) for 6 weeks (ClinicalTrials.gov Identifier: NCT04814719). PPS has shown anti-inflammatory and anti-fibrotic effects in animal models of OA and has been used for many years in veterinary practice . PPS inhibits the expression of TGF-β1, IL-6, TNF-α and fibronectin . Both OA and rheumatoid arthritis typically have some degree of fibrosis associated with them, and the beneficial effects observed are likely a combination of anti-inflammatory and anti-fibrotic effects. It isn’t known if PPS is useful for treating arthrofibrosis.
HA and PRP
Hyaluronic acid (HA) and platelet rich plasma (PRP) injections
There is a lack of quality research supporting the use of hyaluronic acid (HA) and platelet rich plasma (PRP) injections, particularly for treating arthrofibrosis. In fact, both of these treatments carry a theoretical risk of increasing fibrosis. HA is known to have pro-inflammatory  and pro-fibrotic effects  and high levels are associated with fibrosis and inflammation . PRP consists of concentrated cytokines and other factors from the blood, including the major pro-fibrotic cytokine TGF-β. Recent research suggests that PRP induces the activation of myofibroblasts . In addition, the methods used to make PRP vary widely, as do the safety and sterility of the preparations.
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