Transarterial Embolization in Osteoarthritis of the Knee

Mechanism of Action and Current Results

Background: Approximately 5.2 million people in Germany suffer from osteoarthritis of the knee. Minimally invasive embolization of the genicular artery (GAE) was first described in 2015. It reduces pathologically altered synovial vascularization in the periarticular tissue and the associated inflammatory processes. It is thought that this can inhibit the disease process and relieve pain in patients with symptomatic osteoarthritis of the knee who do not respond to conservative treatment. In this review, we assess this technique with regard to its safety and efficacy.

Methods: This narrative review is based on pertinent publications (2015–2025) retrieved by a search in the PubMed/Medline and Google Scholar databases for prospective and retrospective clinical studies and meta-analyses.

Results: 25 studies on GAE have appeared since 2015, among them three randomized controlled trials (RCTs) with sham controls (n = 21; n = 59; n = 58). In a small-scale multicenter RCT (n = 21), GAE reduced pain to a markedly greater extent at 1 month compared to controls (VAS difference 50.1 mm, 95% confidence interval [29.0–72.3]; p < 0.01). Two larger RCTs did not reveal any significant additional benefit compared to sham treatment. In the Australian triple-blind RCT (n = 59) the mean improvement in the KOOS pain score at 12 months was higher in the GAE group (41.3% vs 29.4%), but the difference between groups was not significant. In the Dutch RCT (n = 58), the mean improvement in the KOOS pain score at 4 months was 21.4 points [13.9–28.8] after GAE and 18.4 [11.6–25.1] after sham treatment; the intergroup difference of 3 points was not significant ([−7.1 to 13.0], p = 0.31). Adverse events were rare and generally self-limiting.

Conclusion: Before-and-after studies showed safe pain relief by GAE, but these findings have not been confirmed by the RCTs that have been carried out to date. Current evidence is mixed. Larger-scale, methodologically robust RCTs are needed so that the efficacy of GAE and its role in the treatment of symptomatic knee osteoarthritis can be reliably evaluated.

Cite this as: Collettini F, Fleckenstein FN, Winkler T, Wirtz DC, Perka C, Gebauer B: Transarterial embolization in osteoarthritis of the knee: Mechanism of action and current results. Dtsch Arztebl Int 2026; 123: 97–101. DOI: 10.3238/arztebl.m2025.0221

Osteoarthritis is a global health burden, affecting more than half a billion people worldwide (1). This joint disease, which is already a major public health issue, is becoming even more prevalent as the result of an aging population in combination with rising obesity rates. Osteoarthritis typically follows a slow progressive course, characterized by progressive breakdown of articular cartilage, pain and functional limitations in the affected joints (2). Historically, osteoarthritis was seen as a degenerative joint condition caused by wear and tear, but we now know that its pathogenesis is far more complex. Today, it is understood to be a complex disease affecting the entire joint organ; in addition to mechanical factors, chronic inflammatory processes play an important role (3, 4).

Osteoarthritis of the knee, the most commonly affected joint, accounts for a large proportion of osteoarthritis cases worldwide. In Germany, approximately 18% of the adult population have osteoarthritis of the knee, equating to about 5.2 million affected persons (5). At present, no curative treatment options are available. The numerous existing conservative approaches, both non-pharmacological and pharmacological, have often failed to satisfactorily alleviate the joint pain in the long term (6). The current S2k-level clinical practice guideline of the Association of the Scientific Medical Societies in Germany (AWMF, Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften) recommends a step-by-step approach with conservative measures, such as exercise therapy, weight reduction and pain medication, as the first line of treatment. Surgical procedures, such as total knee replacement (TKR), are only performed on patients with severe symptoms and significant structural changes to the joint (7). In Germany, 16.6% of patients newly diagnosed with osteoarthritis of the knee undergo total knee replacement within the first year (8). However, between 10% and 25% of patients treated with TKR reported persistent pain or functional limitations despite the procedure (9). At the same time, data from large registry studies show that age at the time of arthroplasty is a significant predictor of the risk of revision surgery, with a consistently higher risk for younger patients (10). The rate of revision surgery within three years was about 4% among patients aged under 65, whereas it was about 2% among patients aged 65 years or older (10). An increase in revision surgeries has also been observed in Germany: In 2018, a total of 23 812 revision procedures after TKR were performed, corresponding to an increase of 20.8% compared to 2008 (11). Given these limitations, expanding the therapeutic spectrum by adding effective minimally invasive procedures could be of significant benefit for many patients who are either not eligible for TKR or wish to avoid or delay the procedure.

Angiogenesis, neurogenesis and inflammation are key pathophysiological processes underlying the chronic symptoms of osteoarthritis (12). Osteoarthritis is associated with the formation of new blood vessels (neoangiogenesis) in bone, cartilage and synovium. The extent of neoangiogenesis correlates with the severity of structural changes in the joint and the progression of the disease (13). The formation of new blood vessels in the osteoarthritic joint facilitates the invasion of inflammatory cells, aggravates cartilage destruction and promotes inflammatory responses (12, 14). Growth factors released by activated macrophages stimulate synovial angiogenesis and encourage the growth of nerves into the normally avascular and aneural articular cartilage (12). It is thought that these processes play a major role in the pathogenesis of joint pain and set off a self-reinforcing cascade which is the driving factor underlying osteoarthritis. In light of these findings, neoangiogenesis is considered one of the key therapeutic targets of osteoarthritis management (15).

Embolization of the genicular artery (GAE), also referred to as transarterial periarticular embolization (TAPE), is a novel, minimally invasive approach to the symptomatic treatment of osteoarthritis. The method aims at reducing synovial hyperperfusion in order to dampen inflammatory processes, reduce neovascularization and abnormal neoinnervation, and ultimately alleviate osteoarthritis-related pain (12). In addition to the knee joint, currently the most commonly treated joint, the technique can in principle also be used to treat other joints, such as the hip, shoulder and thumb saddle joints, and the temporomandibular joint (16, 17, 18, 19). Alongside its increasingly widespread clinical use, scientific and public interest in this treatment approach has also grown significantly in recent years (20).

The aim of this review is to systematically present the current body of knowledge on the technique, safety, and effectiveness of GAE in the treatment of osteoarthritis of the knee, incorporating our own experiences gained in everyday clinical practice.

Methods

We reviewed pertinent publications (2015–2025) retrieved by a selective search in the PubMed/Medline and Google Scholar databases for prospective and retrospective clinical trials and meta-analyses. We used the search terms “genicular artery embolization“ OR “transarterial embolization AND knee“ OR “knee osteoarthritis AND embolization“ OR “transarterial microembolization“. The last search was performed on 22 July 2025.

Patient selection and preprocedural work-up

An indication for GAE may be established if there is a lack of satisfactory clinical improvement despite at least three months of adequate conservative treatment, comprising multimodal strategies such as physiotherapy, physical therapy and analgesia,. While there is currently no definitive consensus on contraindications, the following exclusion criteria have been proposed:

• Severe atherosclerotic changes, such as vascular occlusion or stenosis
• Infection of the knee joint
• Known or suspected autoimmune disease or inflammatory rheumatic systemic disease
• General contraindications to angiography (21, 22, 23).

Various patient-reported outcome measures (PROMs) are used for the assessment of knee pain. eTable 1 provides a summary of key PROMs used in research related to GAE (24).

eTable 1

Patient-reported Outcome Measures (PROMs)

Imaging studies for evaluating of the indication for GAE should not date back more than six months prior to the intervention. Conventional imaging should be performed to exclude other joint abnormalities, such as fractures, tumors or axial malpositioning. While magnetic resonance imaging (MRI) of the knee joint is not mandatory for all patients, it can contribute to optimizing patient selection. Computed tomography angiography (CTA) is used in selected patients with known peripheral arterial occlusive disease to assess the extent of the disease and any stenosis.

Anatomical basis and interventional technique

A detailed understanding of the arterial blood supply to the knee joint is essential for performing a safe and effective GAE. The knee joint consists of the medial, lateral and patellar compartments, each of which is supplied by specific arteries (Figure 1).

Figure 1

Schematic representation of the blood supply to the knee joint with clinical relevance for embolization therapy Figure created using BioRender; Zhou, S. (2025), https://BioRender.com/k696c53

First, an ultrasound-guided (typically antegrade) 4-French vascular access is established in the groin (common femoral artery) under local anesthesia. A digital subtraction angiography (DSA) is performed using a 3-F or 4-F guide catheter to identify the genicular arteries. Abnormal synovial vessels can be identified on angiography by the presence of a tumor-like hyperemia (blush), which is most clearly visible in the delayed phase of DSA (Figure 2a). Once the target vessels have been identified, selective probing is performed using a size 1.7-F to 2.0-F microcatheter. In the literature, the use of cone beam computed tomography and alternative access routes, such as the pedal or tibial approach, are described as possible strategies to facilitate probing (25, 26). The embolic agent is selectively applied after angiographic confirmation of abnormal hypervascularization in the target area (Figures b and c) and careful evaluation of potential non-targeted perfusion, especially of cutaneous and muscular collateral branches. Small amounts of the embolic agent are injected by way of pulsed bolus injections through the microcatheter into the hyperemic target vessels to occlude the abnormal vascular bed while maintaining normal blood flow in the genicular arteries. After embolization, a DSA is performed to confirm the resolution of the hyperemic synovial blush (Figures d and e).

Figure 2

Peri- and postinterventional digital subtraction angiography (DSA) of the genicular arteries in medial-dominant osteoarthritis of the knee

The choice of the embolic agent varies and comprises both temporary and permanent embolic agents. The use of the various products differs between geographical regions: While in Asia and Europe preference is given to the use of temporary embolic agents, such as imipenem/cilastatin, in the United States permanent particles are primarily used (23, 27). According to the literature, the size of permanent microspheres ranges between 75 μm and 300 μm. If permanent microspheres are used, it is recommended to apply an ice pack to the skin to prevent off-target embolization of the skin by inducing vasoconstriction of the cutaneous branches (22).

In recent years, new specific temporary microspheres have been developed for this indication and in our Center we mostly use these materials. The best-known products include absorbable gelatin microspheres and lyophilized alginate-based microspheres. In addition, the use of an ethiodized oil-based emulsion for GAE has recently been studied (28).

Clinical results

A total of 25 clinical trials on transarterial embolization in osteoarthritis of the knee have been published to date, including three randomized, controlled trials (RCTs), 13 prospective pre-post studies and ten retrospective case series (eTable 2).

eTable 2

Clinical studies on transarterial embolization in osteoarthritis of the knee (2015–2025)

In the first clinical trial published in 2015, Okuno et al. treated 14 patients with mild to moderate osteoarthritis of the knee with GAE and achieved WOMAC reductions of 73% and 83% at 1 month and 12 months, respectively (48.5 ± 9.4 to 6.0 ± 8.3; p<0.001) (29). A follow-up study published in 2017 included 72 patients with a follow-up period of 24 months. This study too found significant improvements in pain, with WOMAC scores reduced by 50% and 79% after 1 month and 24 months, respectively (43 ± 8.3 to 6,2 ± 6,4; p<0.001) (30). Subsequent studies from various countries confirmed these favorable disease courses (16, 22, 28, 29, 31, 32, 33, 34). The largest single-arm study to date included 444 cases of symptomatic osteoarthritis of the knee. It showed clinically relevant improvements in both pain intensity (measured using the Numeric Rating Scale [NRS]) and all KOOS subscales over a period of 12 months. Median pain intensity decreased from 7 (interquartile range [IQR], 6–8) to 3 (IQR, 1–5) (p<0.001), and the KOOS Quality of Life subscore increased from 19 (IQR, 13–25) to 42 (IQR, 28–57) (p<0.001) (16).

Since the majority of studies lack a control group, it cannot be ruled out that at least part of the observed improvements is attributable to placebo effects or regression to the mean. Further complicating the interpretation of findings from studies without control group is the heterogeneous natural course of osteoarthritis, which depends on structural severity and individual endotype (2). In addition, the observed pre-post improvements must be interpreted with caution, as potential co-interventions (additional training, adjustments made to pain therapy) may also have played a role.

In 2021, Bagla et al. published the first, small RCT (n = 21), comparing GAE to a sham treatment (35). The primary endpoint was the change in pain score on the Visual Analog Scale (VAS) at one month. The patients in the sham group (n = 7) showed no significant improvement (mean VAS reduction of −5%; p = 0.72) and were switched to the treatment group (cross-over design). Patients in the GAE group (n = 14) showed significant VAS reductions of 62% and 49% at one month and 12 months, respectively (–50.1 mm, 95% confidence interval: [–72.3; –29.0]; p<0.01). In the cross-over group (n = 7), a similar clinical course with a 52% VAS reduction at one month was observed after the switch to GAE. In 2023, Landers et al. published the second randomized controlled trial (n = 59), comparing GAE with sham treatment (36). The primary endpoint was the change in the KOOS pain score at 12 months after treatment. The intention-to-treat analysis revealed a 41.3% reduction in the KOOS Pain score in the GAE group compared to a 29.4% reduction in the control group (difference: 11.9%; [−4.2; 28.0]; p = 0.14). Here, one point to note is that during the course of the study, the treatment method was changed from single-vessel embolization to multivessel embolization. A post-hoc subgroup analysis found that patients who underwent multivessel embolization achieved significantly greater improvements in the KOOS domains of physical activity (+48.5; [10.5; 86.4]) and quality of life (+25.0; [4.9; 45.1]) compared to the control group (both p<0.05). Recently, Zadelhoff et al. published the third RCT, comparing GAE to sham treatment in patients with mild to moderate osteoarthritis of the knee (37). The study found that GAE treatment achieved no significantly greater pain relief compared to sham treatment (p = 0.31). It should be noted, however, that the pain reduction achieved in the GAE group (VAS reduction: –22.9%, [–36.4%; –9.4%]) is significantly lower compared to the reductions found in previous studies and meta-analyses, which reported mean reductions of approximately 40.7%. A possible reason for this discrepancy could be the unilateral treatment of patients with bilateral osteoarthritis of the knee. In this situation, biomechanical compensation mechanisms could counteract the therapeutic effect on the treated side. At the same time, this approach makes interpretation of functional scores more difficult, in particular in the KOOS domains “Quality of Life” and “Activities of Daily Living,” given that unilateral treatments produced only minor improvements in the quality of life of patients with bilateral osteoarthritis of the knee. Thus, current evidence is mixed, in particular with regard to findings from high-quality RCTs. Larger-scale, methodologically robust RCTs are needed so that the efficacy of GAE and its role in the treatment of symptomatic knee osteoarthritis can be reliably evaluated. The final results of ongoing RCTs, comparing the efficacy of temporary and permanent embolization, are awaited to provide further insights (32). Two recent meta-analyses found no significant differences between the two approaches (38, 39).

A meta-analysis by Taslakian et al. pooled data from a total of nine studies (40). For each follow-up interval (1, 3, 6, 12, and 24 months), the WOMAC total score fell within the range of –28 to –34 points (p<0.05, in each case). The maximum duration of observation was 24 months. 5.2% of the participating patients underwent total knee replacement within the first two years. Similarly, a systematic review and meta-analysis by Epelboym et al. looked at aggregated data on changes in VAS scores after GAE. It found a decrease in pain intensity after 1, 3, 6, and 12 months on the VAS by –38.5 points [–44.9; –32.0], –36.2 points [–43.0; –29.5], –40.3 points [–49.0; –31.7], and –40.5 points [–54.5; –26.6], respectively. Similar improvements were seen in the WOMAC and KOOS pain scores (38). In the most recent meta-analysis by Chlorogiannis et al., which included findings from a total of 21 studies, GAE was associated with marked clinical improvements in VAS, WOMAC and KOOS pain scores at each time point studied (1, 3, 6, and 12 months) (p<0.05 in each case) (39).

Safety and adverse events

Several studies and systematic reviews looked at the safety of GAE. The meta-analysis by Taslakian et al. reported 29 adverse events in a total of 349 GAE-treated patients from nine studies (8.3%) (40). Most of these were transient minor complications, such as skin discoloration, hematoma at the puncture site, nausea, and vomiting. No serious complications were documented. The length of follow-up periods in the studies analyzed ranged from 1 to 48 months. No late complications were seen in the study with the longest follow-up period (30).

Conclusion

GAE is an innovative procedure in interventional radiology for the symptomatic treatment of osteoarthritis of the knee that has attracted increasing clinical and scientific attention in recent years. Overall, the available studies indicate that GAE has relevant therapeutic potential for selected patients with treatment-resistant osteoarthritis; however, this potential has not yet been satisfactorily supported by evidence from randomized controlled trials. Therefore, GAE should currently be used primarily in clinical studies or on the basis of individualized clinical decision-making in interdisciplinary consultation with the orthopedic and trauma surgery teams. Future randomized controlled trials with clearly defined inclusion criteria, standardized intervention techniques and patient-centered outcomes are essential for evaluating the role of GAE in the management of osteoarthritis of the knee.

Conflict of interest statement

Federico Collettini received financial support and/or consulting fees and/or lecture fees and/or travel expense support from one or more of the following companies: Asahi Intecc Europe B. V., Next Biomedical Co.,Ltd., Terumo Europe NV, Siemens Healthineers Deutschland, Magle PharmaCept, Guerbet, and Sirtex Medical. He is a member of the Advisory Board of Next Biomedical Co., Ltd.

Florian N. Fleckenstein received financial support and/or consulting fees and/or lecture fees and/or travel expense support from one or more of the following companies: Asahi Intecc Europe B. V., Next Biomedical Co., Ltd.; Terumo Europe NV; Cook Medical; Guerbet; and Merit Medical.

Tobias Winkler received consulting fees from Liposphere, Relive, Enlivex, and Pluri. He is a member of the Advanced Therapies in Orthopaedics Foundation (Executive Board).

DCW, CP and BG declare no conflict of interest.

Manuscript received on 15 March 2025; revised version accepted on
24 November 2025

Translated from the original German by Ralf Thoene, M.D.

Corresponding author
PD Dr. med. Federico Collettini

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