Comparative Efficacy of Intra-articular vs. MRI-guided Extra-articular Dextrose Injections in Knee Osteoarthritis Management

Osteoarthritis (OA) is a serious worldwide public health concern, causing increased disability-adjusted life years (DALY), the reasons of which include rising prevalence of obesity and increasing older populations. The knee is one of the most easily injured joint in the body, and knee OA can become a chronic and disabling condition that pose a threat to not only the patient but also his or her caretakers and healthcare resources. The prevalence of knee OA is 5% - 15% in men over 60 years, and 10% - 25% in women aged more than 60.

Knee OA can result from injuries, diseases, or wear and tear from overuse. It refers to structural changes that affect subchondral bone, articular cartilage, menisci, ligaments, synovium, and other joint structures. Currently, there are several conservative management of knee OA, including physiotherapy (therapeutic exercise, diathermy, electrotherapy), oral or topical medications, intra-articular and extra-articular injections, and radiofrequency.

There are various substances used in injections for knee OA, among which are corticosteroid, platelet-rich plasma (PRP), AmnioFix, exosome, dextrose, and hyaluronic acid (HA). Compared with PRP, AmnioFix, exosome, and HA, which are not covered by the health insurance system, dextrose is a readily available and cost-effective substance. The principle of hypertonic dextrose injection, "prolotherapy", is injection of small volumes of the irritant solution at or around the lesion in order to stimulate fibroblast and vascular proliferation, local tissue healing, reduction of joint instability, thus resulting in pain relief. Previous studies have demonstrated that prolotherapy resulted in clinically meaningful sustained improvement of function and pain in knee OA, and there were no severe adverse events related to hypertonic dextrose injection. A study in 2023 showed that among various dextrose concentrations, higher concentrations demonstrated greater improvement of knee OA, thus 20% dextrose is recommended.

Regarding the site of dextrose injection in knee OA, previous studies demonstrated comparable effects of intra-articular and extra-articular injections. The periarticular injections include points around the knee where periarticular nerves exit the joint capsule, and acupuncture points at upper medial and lateral parts of knee joint. A study in 2024 revealed that prolotherapy combining intra-articular with peri-articular perineural injection resulted in better pain alleviation and improvement in knee joint function in knee OA. There are several choices of imaging modality for recognizing the sites of lesion in knee OA, such as X-ray, ultrasound (US), and magnetic resonance imaging (MRI). Radiography is used to assess osteophytes, joint space narrowing, and subchondral sclerosis, but it has limited ability to detect synovial inflammation, joint effusion, soft tissue abnormalities, and early cartilage damage. US can be used to evaluate synovial fluid and cartilage thickness, but not deep structures (e.g. subchondral bone change, meniscus tear, and ACL tear, etc.). On the other hand, MRI is an optimal and accurate imaging choice for visualizing soft tissue as well as deep structures (e.g. ACL, meniscus, etc) in knee OA. The MRI findings of knee OA includes cartilage damage, meniscus tear, bone marrow lesions, synovitis, ligamentous laxity, and osteophytes. The detection of bony lesions can aid intraosseous Infiltrations, and signs of ligamentous laxity also provides target for ligaments injection. However, there is no current evidence on the effectiveness of prolotherapy targeting knee OA lesion sites according to MRI findings.

Because the effectiveness of prolotherapy targeting lesion sites according to MRI findings has not been well established, the investigators aim to investigate whether injecting dextrose into MRI-positive lesion sites is more beneficial for knee OA comparing to intra-articular injections. The investigators hypothesize that MRI could be a good choice for the guidance of prolotherapy targets.

Osteoarthritis (OA) is a serious worldwide public health concern, and there are several conservative management of knee OA. Evidence showed that intra-articular and extra-articular injections are beneficial for knee OA. Compared with PRP, AmnioFix, exosome, and HA, which are not covered by the health insurance system, dextrose is a readily available and cost-effective substance. There are several choices of imaging modality for recognizing the sites of lesion in knee OA, such as X-ray, ultrasound (US), and magnetic resonance imaging (MRI). MRI is an optimal and accurate imaging choice for visualizing soft tissue as well as deep structures. The MRI findings of knee OA includes cartilage damage, meniscus tear, bone marrow lesions, synovitis, ligamentous lesions, and osteophytes. The detection of bony lesions can aid intraosseous Infiltrations. However, there is no current evidence on the effectiveness of prolotherapy targeting knee OA lesion sites according to MRI findings. Thus, the investigators aim to investigate whether injecting dextrose into MRI-positive lesion sites is more beneficial for knee OA comparing to intra-articular injections.

Eligibility Criteria:
Inclusion Criteria:

1. . age between 45 to 80 years old;
2. . meet at least three of the six American College of Rheumatology (ACR) criteria, including age over 50 years, morning stiffness less than 30 minutes, crepitus in passive knee movements, bony tenderness, bony enlargement, and no palpable warmth;
3. . radiologic grading of 2 or 3 according to Kellgren-Lawrence criteria;
4. showing willingness to receive prolotherapy.

Exclusion Criteria:

1. . severe systemic disorders including cancer, uncontrolled diabetes mellitus, sepsis, or cardiopulmonary diseases;
2. . history of anticoagulation therapy, knee injection over the past three months;
3. . history of knee surgery or candidates for knee arthroplasty;
4. . history of drug abuse;
5. . a history of intolerance to prolotherapy;
6. . pregnancy;
7. . infectious arthritis, inflammatory joint diseases, joint dysplasia;
8. Body Mass Index (BMI) greater than 35 kg/m2;
9. . not suitable or no willing to received MRI examination of the knee.