Genicular arterial embolization in knee osteoarthritis: Current evidence, clinical outcomes, and future perspectives

INTRODUCTION

Osteoarthritis (OA) is a prevalent degenerative arthropathy condition involving joint breakdown and structural damage of articular cartilage, joint surfaces, and the underlying subchondral bones due to mechanical stress in the affected area and represents a major contributor to global disability and health expenditure. Over the past three decades, the global burden of OA has increased substantially, with findings from the 2019 Global Burden of Disease study indicating that more than half a billion individuals are currently affected worldwide, representing a greater than two-fold rise since 1990.^[1,2] In India, OA stands as the most prevalent joint disorder, affecting between 22% and 39% of the population, with a markedly higher incidence in women and a sharp rise in prevalence beyond the age of 65 years.^[3] OA arises from the gradual deterioration of the joint’s inherent repair systems due to recurrent microtrauma or structural stress. Routine activities such as frequent kneeling, heavy lifting, or abnormal joint alignment gradually accelerate cartilage degeneration.^[4] While aging, obesity, and female sex are the key risk factors, all people are subject to cumulative biomedical insults, which explains the worldwide and economic significance of knee OA.^[5] Evidence suggests that over half of the individuals in the US with symptomatic knee OA eventually undergo total knee arthroplasty (TKA) in their time.^[6] The parallel rise in obesity and symptomatic OA is anticipated to fuel a continued upsurge in TKA. Despite this trend, a notable segment of the patient population remains unsuitable for operative management due to medical comorbidities, affordability issues, or personal avoidance of surgical approaches.^[7] This narrative review evaluates real-world clinical application and future perspectives pertaining to genicular artery embolization (GAE) in knee OA care.

METHODS

A comprehensive narrative literature search was conducted using “Google Scholar,” “PubMed,” and “Scopus” to identify relevant studies on GAE for knee OA, including literature published between January 2005 and March 2025. Search terms included “genicular artery embolization,” “knee osteoarthritis,” “synovial vascularity,” “angiogenesis,” “interventional radiology,” and “pain management.” Studies were included if they focused on GAE for knee OA and reported information on patient eligibility and treatment outcomes. Most studies included patients with mild-to-moderate knee OA who had ongoing pain despite conservative treatment and confirmed radiographic findings. Outcomes measured included pain scores such as the visual analog scale (VAS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), functional improvement, imaging changes like reduced synovitis, quality-of-life scores, and any reported complications or safety events. Moreover, studies were excluded if they were commentaries, animal studies, conference abstracts, or articles not directly related to GAE in knee OA.

PATHOPHYSIOLOGY OF OA

OA is no longer regarded as a mere “wear-and-tear” phenomenon; rather, it represents a complex degenerative joint disease arising from interdependent mechanical, inflammatory, metabolic, and age-related processes that progressively impair joint homeostasis and structural integrity.^[8] In the last thirty years, the comprehension of osteoarthritis pathogenesis has significantly advanced, acknowledging inflammation as a crucial pathological element of joint deterioration, corroborated by initial clinical observations and subsequent molecular research illustrating cytokine-mediated activation of cartilage-degrading enzymes that propel disease progression.^[9] Many people with OA exhibit synovitis, which is closely tied to increased pain and the worsening of joint damage over time.^[10] The progression of OA is governed by an intricate cytokine network, notably involving interleukin (IL)-1β, IL-6, IL-17, and tumor necrosis factor-a (TNF-a), which maintain a state of persistent low-grade inflammation and activate nuclear factor-kappa B and Mitogen-Activated Protein Kinase (MAPK) signaling cascades. These molecular pathways stimulate the release of matrix-degrading enzymes, alter chondrocyte metabolic function, and suppress regenerative capacity. In addition, the dynamic interaction between CD4⁺ T-cell subsets and chondrocytes amplify pro-inflammatory signaling within the joint, fostering cartilage breakdown, subchondral bone remodeling, and chronic disease progression.^[11]

Aging and chronic inflammation further contribute through the process of “chondrosenescence,” defined as the age-dependent decline in chondrocyte function and viability.^[11,12] Senescent chondrocytes lose mitochondrial function, experience telomere loss, and show abnormal gene regulation, driving inflammatory cytokine release and matrix-degrading enzyme synthesis that worsens cartilage damage.^[13,14] Alterations in circadian rhythm contribute to the loss of chondrocyte equilibrium, with downregulation of the clock gene BMAL1 in osteoarthritic cartilage linking disrupted chronobiology to oxidative damage and progressive cartilage deterioration.^[15,16] Lifestyle factors such as obesity, poor diet, and physical inactivity amplify joint loading and systemic inflammation, accelerating OA progression.^[17,18]Conversely, moderate physical activity improves mobility, enhances muscular support, and exerts anti-inflammatory effects, slowing symptomatic and structural decline.^[19] However, sustained high-impact or elite-level athletic activity may predispose individuals to post-traumatic OA, underscoring the importance of joint-protective exercise strategies.^[20] Within this inflammatory microenvironment, synovial neovascularization becomes a defining pathological feature in progressive OA. GAE is designed to selectively target and occlude these abnormal neovessels, while preserving the normal physiological vascular supply of the knee. The therapeutic premise of GAE lies in reversing the hyper vascular and inflamed synovial state, thereby restoring a more physiologic vascular balance. This is achieved by mechanically obstructing the pathological blood flow, leading to reduced inflammatory activity and associated pain [Figure 1].

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Figure 1:

Overview of genicular artery embolization for Osteoarthritis (OA). (a) Typical vascular anatomy of the knee. (b) Synovial neovascularization and inflammation in OA. (c) Selective embolization of abnormal genicular branches using a microcatheter to reduce synovial hypervascularity while preserving native perfusion.

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EVOLUTION AND RATIONALE OF GAE IN KNEE OA

GAE was first utilized to manage recurrent hemarthrosis following knee arthroplasty, and its success in this setting paved the way for its development as an innovative therapy for knee OA. It was first documented as an effective intervention to control intra-articular bleeding.^[21,22] The clinical efficacy of transcatheter arterial embolization in pain reduction and enhancing joint mobility in individuals with mild-to-moderate knee OA was first established by Okuno et al. in 2015, representing its inaugural use as a treatment approach for OA.^[23] A prospective analysis by Okuno et al. (2017) involving 72 individuals with mild-to-moderate knee OA demonstrated significant and sustained enhancements in pain and joint function after transcatheter arterial embolization, with therapeutic benefits lasting up to 3 years and no major adverse events, suggesting a durable and safe alternative to conventional therapies.^[24] The GENESIS trial demonstrated that GAE using permanent microspheres provided sustained pain relief and functional enhancement across a 2-year observational timeframe in participants experiencing grade II and grade III knee OA. The study also confirmed a significant reduction in synovitis without major complications, reinforcing the long-term safety and therapeutic potential of GAE.^[25] In addition, a 2-year prospective Investigational Device Exemption (IDE) trial demonstrated that GAE provides nearly one in two patients exhibiting moderate-to-severe structural degeneration of the knee joint based on Kellgren–Lawrence (KL) grading (grades II-IV), with no new adverse events reported beyond 12 months, confirming its long-term safety and efficacy.^[26] Recently, long follow-up results from the GENESIS trial confirmed that GAE provides lasting pain relief and post-rehabilitation in grade II and grade III knee OA without late adverse events. Moreover, patients undergoing subsequent knee arthroplasty showed no procedural complications, affirming GAE’s long-term safety and compatibility.^[25] The conceptual basis for employing GAE in OA treatment is its ability to interfere with the self-perpetuating loop of inflammation, pathologic vascular proliferation within the synovium, and pain-generating nerve signaling.^[27] In OA, cytokines (such as IL-6, IL-18, granulocyte-macrophage colony-stimulating factor, TNF-a, and vascular endothelial growth factor) stimulate aberrant vascular proliferation within the synovium and periarticular tissues, contributing to sustained inflammation and pain sensitization.^[27,28] By selectively embolizing hypertrophic genicular arterial branches that supply these inflamed regions, GAE effectively reduces synovial hypervascularity, inflammatory mediator release and sensory nerve irritation, leading to sustained symptom relief. In addition, by preserving the primary joint vasculature and targeting only pathological neovessels, GAE achieves therapeutic efficacy while maintaining tissue viability.^[28]

PATIENT SELECTION CRITERIA AND PRE-PROCEDURAL EVALUATION FOR GAE

In optimizing outcomes with GAE for knee OA, thoughtful patient selection remains essential. This minimally invasive intervention is best suited for individuals who continue to experience debilitating knee pain despite exhaustive conservative treatments and either lack eligibility for surgical procedures due to medical constraints or prefer to avoid operative interventions altogether.^[29,30] Current evidence reveals limited correlation between baseline patient characteristics and clinical outcomes following GAE, as early studies lacked robust subgroup analyses. Nonetheless, GAE has demonstrated consistent clinical success across patients with mild-to-severe OA.^[31] The eligibility criteria for ideal candidates undergoing GAE continue to evolve with advancing clinical evidence. Typically, participants included in clinical studies are middle-aged and older adults diagnosed with grade II or III knee OA, characterized by a KL grade between 1 and 4 on radiographic assessment. Ideal candidates are those experiencing ongoing knee pain rated ≥40 mm on the VAS that remains unresolved after 3–6 months of optimized non-surgical management, including pharmacological therapy, rehabilitative exercises, lifestyle interventions, and who are either medically unfit for or elect to avoid surgical procedures.^[23-26,30] Patients unsuitable for GAE include those with severe peripheral arterial disease (PAD), as the genicular vessels may be essential for limb perfusion. The patient selection criteria for GAE are mentioned in Table 1.^[25,26] The procedure is also contraindicated in the presence of active knee infection or advanced renal dysfunction. Moreover, individuals with normal imaging findings or pain related to systemic inflammatory or non-osteoarthritic conditions are typically excluded.^[32]

A detailed clinical assessment before GAE is essential to establish a baseline profile and facilitate objective comparison during follow-up. Pain intensity is typically recorded using the VAS, while functional status and joint-related symptoms are captured through validated OA instruments such as the WOMAC and Knee Injury and Osteoarthritis Outcome Score (KOOS). Broader health status and post-procedural recovery may be evaluated using generic quality-of-life measures like the SF-36. In addition, patient-reported outcome frameworks including the EuroQol Five-Dimension Questionnaire (EQ-5D), WOMAC, KOOS, and the OsteoArthritis of Knee and Hip Quality of Life questionnaire (OAKHQOL) questionnaire offer valuable insight into overall well-being, mobility, functional independence, and disease-specific quality-of-life domains following treatment.^{[23,25,33,34]} The whole-organ magnetic resonance imaging (MRI) score can be used to establish a baseline and monitor post-treatment outcomes.^[35] Pre-operative vascular mapping using computed tomography or magnetic resonance angiography is generally unnecessary since vascular mapping is performed during diagnostic angiography. However, screening for PAD is crucial because genicular arteries may serve as collateral vessels in such cases.^[23,25,26] Patient demographics, body mass index, comorbidities, and medication history should also be documented, as obesity and metabolic disorders may influence procedural outcomes.^[36] Patients with advanced PAD should be approached with caution, as the genicular arterial network may act as a compensatory conduit for distal circulation in cases of lower-limb ischemia, and embolization could jeopardize peripheral tissue perfusion.^[25,37]

CLINICAL EFFICACY AND SAFETY PROFILES OF GAE

Every GAE procedure reported achieved complete technical success, indicating that the target genicular vessels were successfully accessed and embolized as intended without deviation from the planned procedural approach. Detailed procedural techniques have been outlined in earlier publications. A total of 18 out of 38 patients (47.4%) achieved a ≥50% improvement in symptoms at the 24-month follow-up.^[2] GAE has demonstrated consistently high technical success rates and notable short- to mid-term reductions in pain, reflected by significant improvements in VAS, WOMAC, and KOOS scores. Both temporary and permanent embolic materials have shown comparable clinical outcomes. However, heterogeneity in target vessel selection, embolic particle size, and procedural methodologies limits direct cross-study comparisons and meta-analytical evaluation. Reported adverse events are infrequent, typically mild, and resolve spontaneously without lasting effects.^[26] The MOTION trial compares GAE with corticosteroid injections for knee OA, expecting 65% versus 40% success, demonstrating superior pain relief, safety, and long-term clinical benefit over 24 months.^[31] A recent analysis demonstrated that post-GAE, the number of patients requiring opioids and NSAIDs decreased by 27% and 65%, respectively, suggesting durable pain relief and improved quality of life.^[38] The LIPIOJOINT-1 trial reported complete technical success with GAE performed using an ethiodized oil-based emulsion, resulting in substantial pain and functional improvement in 73% of participants after 3 months.^[39] A sham-controlled study conducted over 4 months found comparable pain improvement between groups, with KOOS pain scores improving by 21.4 points after GAE and 18.4 points following the sham procedure, indicating no significant difference in short-term outcomes.^[40] GAE is generally well tolerated, as it reports a low incidence of serious adverse events. The most frequent complications are minor and transient access site hematoma, transient skin discoloration or erythema, mild local pain, and rare transient sensory changes, while major complications are uncommon in published cohorts. Overall technical success rates are high.^[38,41] In our Indian setting, GAE demonstrated notable clinical efficacy at the 3-month follow-up, with median VAS scores decreasing from 7 to 3.5 and WOMAC scores improving from 53 to 23.5, indicating substantial pain reduction and functional recovery in 80% of patients.^[42]

Novel minimally invasive approaches, including GAE and radiofrequency ablation, have attracted growing academic and clinical interest as joint-preserving therapeutic options for mitigating pain and enhancing functional outcomes in individuals with knee OA.^[40,43-45] A comprehensive meta-analysis conducted by Torkian et al. critically evaluated the role of GAE as a novel vascular intervention aimed at modulating inflammation and pain in osteoarthritic knee joints.^[38] The study included 11 studies involving 225 patients and found marked enhancement in both VAS and WOMAC scores post-GAE, with the mean difference in VAS scores ranging from 32 points within the 1^st week to 58 points after a 2-year follow-up, indicating an 80% improvement.^[38] GAE was initially introduced to manage recurrent post-operative hemarthrosis following TKA and has since emerged as a minimally invasive alternative, offering promising outcomes in reducing pain, inflammation, and vascular complications associated with post-operative knee conditions.^[46] Furthermore, GAE effectively reduces synovial hypervascularity before TKA in individuals with hemophilia, establishing its safety and utility as an adjunctive intervention in surgical management. The procedure significantly decreases synovial vascularity without increasing the risk of post-operative bleeding, supporting its potential as a complementary intervention in complex knee conditions.^[47] Although GAE entails higher costs, evidence suggests that it achieves a high success rate by mitigating pain symptoms and promoting functional restoration of the knee joint in osteoarthritic patients. Overall, despite the added expense, GAE demonstrates promising clinical benefits that may justify its cost from a long-term health perspective.^[48]

FUTURE DIRECTIONS AND INTEGRATION OF GAE INTO MULTIMODAL OA MANAGEMENT

GAE stands out as a novel interventional strategy in the therapeutic landscape of OA, particularly for patients who are refractory to conventional non-surgical therapies and are not ideal surgical candidates. Despite encouraging early clinical results, GAE remains a developing intervention, and further research is warranted to establish its long-term safety, efficacy, and integration into multimodal OA management.^[36,38] Although symptomatic improvement after GAE has been consistently reported, the biological mechanisms underlying this response continue to be elucidated. Current evidence suggests that therapeutic benefit may derive from targeted modulation of synovial angiogenesis and inflammatory nociceptive signaling, yet knowledge gaps remain regarding the relationship between the extent of embolization, baseline disease severity, and sustained pain control. Intriguingly, several studies indicate that GAE may produce substantial symptomatic relief without parallel changes on structural imaging, reinforcing the concept that vascular-inflammatory modulation rather than cartilage restructuring underpins clinical benefit. Opportunities for refinement in patient selection and procedural optimization are expanding with technological advancements. Emerging imaging platforms such as optical coherence tomography and dynamic contrast-enhanced MRI hold promise for improving pre-procedural mapping, enabling more precise identification of pathological neovessels, and allowing longitudinal monitoring of vascular remodeling following embolization.^[49] Beyond knee OA, emerging evidence suggests that GAE may also provide benefit in overuse syndromes and periarticular tendinopathies, such as pes anserinus or patellar tendinopathy, broadening its therapeutic scope. As clinical evidence continues to grow, GAE has the potential to evolve from a pain-modifying adjunct to a precision-based, disease-modifying intervention within musculoskeletal medicine.^[50]

CONCLUSION

GAE represents a transformative advance in OA management, shifting therapy from symptomatic relief to vascular-pathology targeting. As OA prevalence increases with aging and obesity, GAE offers a minimally invasive alternative to TKA by selectively occluding aberrant neovessels that drive inflammation and pain. Clinical studies reveal sustained reductions in pain and improved joint function lasting up to 2 years among patients resistant to conservative measures, highlighting its role as both a substitute and adjunct to surgery. Originally applied in post-operative hemarthrosis, GAE’s success in chronic OA reinforces the vascular-inflammatory interplay underlying disease progression. Despite promising outcomes, uncertainties persist regarding its long-term durability, optimal candidate profiles, and economic viability. Future research should emphasize high-quality randomized trials, optimization of embolic materials, use of advanced imaging for procedural accuracy, and identification of molecular predictors of response. Beyond OA, GAE’s expanding role in tendinopathies, synovitis, and sports-related microvascular disorders reflects its versatility within musculoskeletal care. Supported by technological and interdisciplinary progress, GAE is emerging as a cornerstone of personalized, minimally invasive treatment, delivering enduring pain relief and functional recovery.