Data review presents geniculate artery embolization as an emerging minimally invasive technique for knee OA

Osteoarthritis (OA) is characterized by the breakdown of articular cartilage, subchondral bone remodeling, osteophyte formation, and synovial inflammation, which leads to chronic pain and reduced quality of life. Nonoperative treatment modalities include oral analgesics and physical therapy. Geniculate artery embolization (GAE) is an emerging minimally invasive technique designed to target aberrant vascular and inflammatory responses in knee OA. This review explores the pathophysiology of OA, the rationale for GAE, current evidence, and future directions for this novel therapeutic approach.

Technique overview
During GAE, a microcatheter technique is used to selectively embolize hypervascular synovial regions. Typically, the superior lateral, superior medial, inferior lateral, and inferior medial branches’ genicular arteries are targeted using fluoroscopic guidance. The technique begins with vascular access, most commonly the ipsilateral femoral artery. Angiography is performed from the distal superficial femoral artery above the origin of the descending genicular artery using digital subtraction angio-graphy and, when available, cone-beam CT to delineate the genicular arterial anatomy and identify hyperemic target vessels corresponding to the site of pain or pathology. A microcatheter (1.7-2.4 F) is advanced selectively into each target genicular artery. Radiopaque skin markers may be used to localize pain and guide vessel selection. Before embolization, intra-arterial nitroglycerin may be administered to increase flow and facilitate identification of target vessels, especially in cases of vasospasm. Embolic agents are diluted with contrast and saline and injected in small aliquots (0.1-0.4 mL) under fluoroscopic guidance until pruning of abnormal neovessels is achieved, while maintaining normal arterial inflow.

Use cases and efficacy data
The pathogenesis of knee OA involves inflammatory mediators such as cytokines and adipokines that exacerbate joint damage. Increased angiogenesis is observed in the synovium, osteophytes, and at the osteochondral junction, driven by pro-angiogenic factors such as vascular endothelial growth factor and β-nerve growth factor. The increased vascularization and subsequent inflammation can lead to endothelial dysfunction and altered vascular responsiveness, contributing to compromised blood flow and ischemia in the subchondral bone, thus perpetuating the cycle of joint damage in OA. The rationale for GAE lies in its ability to reduce the inflammatory and catabolic processes driven by aberrant angiogenesis within the osteoarthritic joint. By selectively embolizing the genicular arteries, GAE diminishes the blood supply to the hypervascular synovium and subchondral bone, thereby alleviating pain and inflammation. GAE is performed using non-permanent embolic agents like antibiotic imipenem/cilastatin beads or permanent embolic agents like proprietary microspheres.

It is possible that GAE could be a safe and effective intervention in providing short-term pain relief in patients with mild to moderate arthritis, but there is no definitive support in the literature. Furthermore, any evidence of efficacy in patients with severe OA is limited. Several uncontrolled prospective studies have shown 60-80% pain reduction on the visual analog scale at six and 24 months after GAE, suggesting a clinically meaningful and durable effect. However, significant protocol heterogeneity, small sample sizes, and study design flaws contribute to variable outcomes.

There are only a few randomized, controlled trials (RCTs) evaluating GAE. In one RCT, Bagla et al. reported significant pain improvement within one month. This study was limited by a smaller sample size, as there were only 14 patients in the sham and seven patients in the GAE groups. A second RCT from Landers et al. demonstrated a nonsignificant difference in Knee Injury and Osteoarthritis Outcome Scores for pain between treatment and control groups. Van Zadelhoff et al. conducted an RCT of sham versus GAE embolization and reported no difference between groups at four months.

Safety and cost considerations
GAE for knee osteoarthritis is generally considered a safe procedure. However, it is associated with several adverse reactions. The most frequently reported side effects were temporary, such as skin discoloration and access site hematomas, affecting up to 80% of patients. Minor complications such as erythema (11%), paresthesia (1%), plantar sensory paresthesia, and fever (0.5%) have also been documented. Severe adverse events like deep vein thrombosis are rare. One study reported plantar sensory paresthesia in 10% of patients, which resolved within 14 days. Despite the high rate of minor adverse events, GAE is considered a safe intervention.

Introducing GAE for the treatment of knee OA has significant financial implications, particularly when considering its cost-effectiveness compared to cortisone injections and NSAIDs. According to an analysis by Kwak et al., the direct cost of corticosteroid injection is approximately $70, while the cost of GAE is approximately $5,000 in the outpatient setting and $11,000 in the inpatient setting.

Safety, efficacy and direct financial cost of GAE should be studied in a prospective, randomized trial with sham and corticosteroid injections, as any invasive procedure with a high financial burden should be put to strict testing before widespread usage. Physicians should consider the financial impact of GAE on the healthcare system and potential complications in future invasive procedures, and patients should be informed about the limited data on both short- and long-term outcomes following GAE.

Ajay Srivastava, MD, FAAOS, is an adult reconstruction surgeon and director of the McLaren Flint orthopaedic surgery residency program at McLaren Flint Medical Center and Hurley Medical Center in Flint, Michigan.

Kevin Adik, MD, is an orthopaedic surgery resident at the Michigan State University-McLaren Health Care program in Flint, Michigan.

Mohammed K. Alsarraj, MD, is an orthopaedic surgery resident at the Michigan State University-McLaren Health Care program in Flint, Michigan.

Abdullah Alsarraj, BMS, is a biomolecular sciences student at the University of Michigan.

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