The primary objective of this study is to evaluate and compare the effectiveness of ultrasound-guided combined intra-articular and peri-articular platelet-rich plasma (PRP) injections with intra-articular PRP injections alone in patients with chronic knee osteoarthritis (OA). The study specifically examines the effects of these treatment approaches on pain, physical function, activities of daily living, and structural parameters, including medial collateral ligament (MCL) thickness and distal femoral cartilage thickness.
Osteoarthritis is a degenerative joint disease characterized by progressive cartilage erosion, osteophyte formation, and subchondral sclerosis, leading to pain, stiffness, and functional disability. It is the most common form of arthritis and a leading cause of disability worldwide, affecting approximately 300 million individuals. Although the knee is the most frequently involved joint, OA is now recognized as a whole-joint disease, involving not only cartilage degeneration but also pathological changes in subchondral bone, synovium, and surrounding extra-articular structures.
Platelet-rich plasma is an autologous concentration of platelets suspended in a small volume of plasma and contains a variety of bioactive growth factors, such as transforming growth factor-beta (TGF-β), platelet-derived growth factor (PDGF), and vascular endothelial growth factor (VEGF). These factors play a crucial role in promoting cell proliferation, angiogenesis, and tissue repair. In knee OA, PRP has been shown to reduce matrix metalloproteinase (MMP) activity, particularly MMP-13, enhance endogenous hyaluronic acid production, and support chondrogenesis. Although intra-articular PRP injections are widely accepted as a safe and effective treatment and have demonstrated superiority over placebo and hyaluronic acid in long-term follow-up studies, most existing research has focused exclusively on intra-articular applications.
Knee OA is a multifactorial condition frequently associated with extra-articular pathologies, including ligament laxity, peri-articular edema, and soft tissue inflammation. Limiting treatment to the intra-articular space alone may therefore overlook these important contributors to pain and functional impairment. Emerging evidence suggests that a combined treatment approach targeting both intra-articular and peri-articular structures may provide superior outcomes in terms of pain reduction and functional improvement.
This prospective randomized controlled trial will include 42 patients aged 40-65 years with chronic knee OA classified as Kellgren-Lawrence grade 2 or 3. Participants will be randomly assigned to one of three groups: a control group receiving conservative treatment only (exercise therapy and lifestyle modifications), a group receiving conservative treatment plus ultrasound-guided intra-articular PRP injections, and a third group receiving conservative treatment plus combined ultrasound-guided intra-articular and peri-articular PRP injections targeting the MCL and pes anserinus regions.
Clinical outcomes will be assessed using validated instruments, including the Visual Analog Scale (VAS), the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and the Short Form-36 (SF-36) Quality of Life Scale. In addition, ultrasonographic measurements of MCL thickness and distal femoral cartilage thickness will be performed to evaluate structural changes. By investigating the additional value of peri-articular PRP injections, this study aims to contribute to the development of more comprehensive and effective injection protocols for the management of chronic knee osteoarthritis.
Age between 40 and 65 years.
Patients with significant medial knee pain who have not responded to conservative treatment for at least 3 months.
Patients diagnosed with knee osteoarthritis according to the American College of Rheumatology (ACR) criteria and with Kellgren-Lawrence grade 2 or 3 radiographic osteoarthritis.
Intact cognitive function.
History of previous knee trauma or surgery.
Physical therapy, intra-articular steroid, or hyaluronic acid injections in the knee within the last 3 months.
Active oncological diseases.
Local infection, sepsis, wounds, or scars in the injection area.
Parallel
Conservative Therapy
BehavioralPatients will receive guidance on conservative exercise therapy and lifestyle modifications. Exercise instruction forms will be provided, and patients will be shown how to perform the exercises correctly. Strengthening, stretching, and joint range of motion exercises targeting the quadriceps and hamstring muscle groups will be performed twice daily for 10 repetitions throughout the treatment period. Adherence will be monitored during follow-up visits.
Intra-Articular PRP
Procedure/SurgeryPatients will receive intra-articular platelet-rich plasma (PRP) injections three times at one-week intervals. Following the PRP injections, patients will receive standard post-procedure recommendations, including resting the knee joint for 1-2 days, avoiding aggressive exercise, refraining from using nonsteroidal anti-inflammatory drugs (NSAIDs), and applying warm compresses as needed.
Peri-Articular PRP
Procedure/SurgeryPatients will receive peri-articular platelet-rich plasma (PRP) injections three times at one-week intervals. Following the PRP injections, patients will receive standard post-procedure recommendations, including resting the knee joint for 1-2 days, avoiding aggressive exercise, refraining from using nonsteroidal anti-inflammatory drugs (NSAIDs), and applying warm compresses as needed. Peri-articular injections will be administered under ultrasound (USG) guidance to the origin and insertion sites of the medial collateral ligament (MCL), relevant joint areas, and the insertion points of the pes anserinus tendons.
VAS (Visual Analog Scale)
The visual analog scale (VAS) is a widely accepted measurement tool in the scientific literature used to quantify subjective variables that cannot be directly measured numerically. It consists of a 100-mm horizontal line, with each end representing the extreme limits of the parameter being assessed, ranging from no pain to very severe pain. Patients are asked to mark the point on the line that best reflects their current pain intensity. The distance measured from the no-pain endpoint to the patient's mark indicates the level of pain. The VAS is a safe, easy-to-use, and valid instrument for assessing pain intensity.
WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index)
The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) is a valid and reliable disease-specific instrument widely used to assess disability in patients with osteoarthritis. It consists of three subscales: pain (5 items), stiffness (2 items), and physical function (17 items). Each item is scored on a Likert scale ranging from 0 to 4, reflecting the level of impairment. Subscale scores are calculated separately and combined to yield a total score ranging from 0 to 100, with higher scores indicating increased pain and stiffness and greater impairment in physical function. The Turkish validity and reliability of the WOMAC were established by Tüzün and colleagues.
SF-36 (Short Form 36 Health Survey)
The Short Form-36 (SF-36) is a widely used instrument for assessing patients' overall health status and quality of life, with established validity and reliability in Turkish populations. The scale consists of 36 items across 8 subscales: physical functioning, role limitations due to physical health, bodily pain, general health, vitality, social functioning, role limitations due to emotional health, and mental health. Each item is scored individually, and scores are calculated to produce a total score ranging from 0 to 100, with higher scores indicating better quality of life and lower scores indicating poorer quality of life.
Distal femoral cartilage thickness
The distal femoral cartilage thickness of all participants will be assessed by the same researcher experienced in musculoskeletal ultrasonography using an ultrasound device (Logiq P5, GE Medical Systems, USA) equipped with a linear probe operating at a frequency of 5-12 megahertz (MHz). Measurements will be performed with participants in the supine position and knees in maximum flexion. The ultrasound probe will be positioned perpendicular to the articular surface of the femur by placing it transversely on the upper edge of the patella. Cartilage will be identified as a hypoechoic structure located between the suprapatellar fat pad and the bone cortex. Thickness measurements will be taken at three sites: the midpoint of the medial condyle, the intercondylar notch, and the lateral condyle. Measurements will be based on the distance between the bone-cartilage interface and the cartilage-fat pad interface.
Medial Collateral Ligament thickness
The medial collateral ligament (MCL) of all participants will be assessed by the same researcher experienced in musculoskeletal ultrasonography using a linear probe ultrasound device (Logiq P5, GE Medical Systems, USA) operating at a frequency of 5-12 megahertz (MHz). During assessment, participants will be positioned supine with their knees fully extended. After visualizing the joint space, the MCL will be imaged in the vertical plane along the medial side of the knee. Thickness measurements will be taken at two points: approximately 1 cm proximal to the joint line on the femoral side and 1 cm distal to the joint line on the tibial side.
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