Review by: Robert Wu, 2020

Introduction

Osteoarthritis of the knee is the most common cause of disability in the lower limb in adults over 50 years old, impacting the lives of more than 30 million Americans alone. In more severe cases, patients may experience persistent pain that disrupts sleep or experience knee instability that lead to further disability from falls. Treatment for advanced stage knee osteoarthritis is generally treated with arthroplasty or knee replacement surgery, while mild to moderate osteoarthritis is treated symptomatically with exercise, pain medications, steroid injections. These treatments are not without side effects, however, as chronic medication use may lead to organ dysfunction, opiate addiction and GI ulcers while steroid injections generally require multiple administrations and have mixed efficacy.  

The pathogenesis of osteoarthritis was previously thought to be due to wear and tear of the joint. We now know that pathogenesis also involves chondrocytes and inflammatory cells in surrounding tissues which degrade and remodel bone.  New research suggests that angiogenesis also occurs in osteoarthritis. Angiogenesis helps to create a proinflammatory environment that enables chondrocytes to break down cartilage.  In addition, research has linked angiogenesis in the synovium and periarticular bone to the growth of new sensory nerves.  When stimulated by chemical or mechanical means, these nerves are thought to contribute to osteoarthritis pain.    

Prior case reports have demonstrated that transcatheter arterial embolization has been successful in treating refractory tendinopathy and adhesive capsulitis based on the mechanism aforementioned. This prospective, single institution, non-randomized clinical study assesses the efficacy and adverse effects of transcatheter arterial embolization on chronic knee pain due osteoarthritis.

Study Population and Treatment Protocol

From June 2012 to December 2013, this study enrolled 14 subjects (8 female and 6 male) with a mean age of 65.2 years (range 49-76 years) and was conducted at Edogawa Hospital at Tokyo, Japan. Patients included had moderate to severe knee pain resistant to 3 months of conservative treatment, while those with severe enough OA to be candidates for total knee arthroplasty, local infection, malignancy, advanced atherosclerosis, rheumatoid arthritis, and prior knee surgery were excluded.  

For the embolization technique, a 3F introducer sheath helped establish ipsilateral femoral access after which a 3F angiographic catheter was introduced into the popliteal artery so that 3 – 5 ml iodinated contrast could opacify the genicular arteries and neovascular vessels. Once the abnormal vessels were located, they were selected for using a 2.4F microcatheter that was inserted through the 3F catheter and embolized with imipenem/cilastatin sodium (IPM/CS) in 11 cases and 75 Embozene microspheres in 3 cases.

Data Collection and Statistics

Dunnett’s post hoc test was used to determine changes in the WOMAC score from prior to the procedure to 1, 4, and 12 months post procedure. The Western Ontario and McMaster University Osteoarthritis Index (WOMAC) questionnaire uses 24 questions on daily activities to produce three subscores for pain, stiffness, and physical function that when totaled is the total WOMAC score. Additionally, pain symptoms and use of other therapies were also evaluated at baseline, 1, 4, and 12 months post procedure.   

Results and Outcomes

Technical success rate was 100%. No adverse events, tissue necrosis, dermal ulcers, ligament rupture, or peripheral paresthesia occurred.  One patient, however, experienced moderate subcutaneous hemorrhage at the puncture site that resolved in one week. The average WOMAC pain score decreased from 12.2 ± 1.9 to 3.3 ± 2.1 1 month post procedure to 1.7 ± 2.2 4 months post procedure (p < 0.001). The mean WOMAC total score decreased from 47.3 ± 5.8 to 11.6 ± 5.4 at 1 month, and to 6.3 ± 6.0 at 4 months (p < 0.001). Continued improvement in WOMAC scores were seen in most patients at final follow up which averaged 12 ± 5 months (range 4-19 months). Changes in pain symptoms as well as use of NSAIDs and HA injections are summarized in Table 1.

Table 1: Progression of pain symptoms and additional pain treatment utilization

 

Pre-Procedure

1 Month Post Op

4 Month Post Op

12 Month Post Op

Pain during walking

11

2

4

12

Pain with stairs

14

5

2

Patients receiving NSAIDs

10

4

1

1

Patients receiving HA injection

6

0

1

Conclusion

The pain from osteoarthritis is currently not well understood as cartilage, the primary site of pathology in OA, lacks pain receptors.  This present study suggests that abnormal neovessels supplying the synovium, periosteum, infrapatellar fat pad, and medial meniscus base play a significant role in the pathogenesis of pain in OA since embolization of the neovessels supplying these structural elements provided pain relief. Two mechanisms for pain relief from neovascular embolization have been proposed because pain symptoms were significantly relieved at two time points: immediately after embolization and then again several weeks or months later. It has been proposed that the immediate pain relief is due to reduced sensory nerve stimulation that occurs with decreasing abnormal blood flow.  On the other hand, later pain improvement was attributed to a reduction in the influx of inflammatory cells into synovial tissues. 

The present study possesses some limitations.  Given the small cohort size and relatively short follow up period, the incidence of complications could not be adequately determined. Sources of potential bias include the lack of blinding patients to treatment, lack of a control group, and ability for patients to continue pain relief therapies used before embolization.  Future research is needed to validate this experiment and to better explore possible complications over a longer followup period.

References

  1. Power SP, Cairns B, Prabhudesai V, et al. Genicular Artery Embolization for Recurrent Hemarthrosis of the Knee Following Total Knee Arthroplasty: A Single Centre Experience: Canadian Association of Radiologists Journal. Published online March 23, 2020. doi:10.1177/0846537119899550
  2. Bagla S, Piechowiak R, Hartman T, Orlando J, Del Gaizo D, Isaacson A. Genicular Artery Embolization for the Treatment of Knee Pain Secondary to Osteoarthritis. Journal of Vascular and Interventional Radiology. 2020;31(7):1096-1102. doi:10.1016/j.jvir.2019.09.018
  3. Landers S, Hely R, Page R, et al. Genicular Artery Embolization to Improve Pain and Function in Early-Stage Knee Osteoarthritis—24-Month Pilot Study Results. Journal of Vascular and Interventional Radiology. 2020;31(9):1453-1458. doi:10.1016/j.jvir.2020.05.007
  4. Landers S, Hely A, Harrison B, et al. Protocol for a single-centre, parallel-arm, randomised controlled superiority trial evaluating the effects of transcatheter arterial embolisation of abnormal knee neovasculature on pain, function and quality of life in people with knee osteoarthritis. BMJ Open. 2017;7(5):e014266. doi:10.1136/bmjopen-2016-014266
  5. Okuno Y, Korchi AM, Shinjo T, Kato S. Transcatheter Arterial Embolization as a Treatment for Medial Knee Pain in Patients with Mild to Moderate Osteoarthritis. Cardiovasc Intervent Radiol. 2015;38(2):336-343. doi:10.1007/s00270-014-0944-8