The Efficacy and Safety of a Single-Dose Hyaluronic Acid Injection in the Treatment of Knee Osteoarthritis

Efficacy and Safety of a Single-Dose Hyaluronic Acid Injection in Adults With Symptomatic Knee Osteoarthritis: A Retrospective Study

HA therapy typically consists of several intra-articular injections administered at weekly intervals. A single-dose IA-HA treatment offers patients and physicians a treatment option that involves both lower costs and fewer clinic visits. Furthermore, considering the administration procedure, we believe that single-dose therapy helps reduce the risk of potential side effects.

In light of this information, our study aims to retrospectively evaluate the efficacy and safety of HA in patients with symptomatic knee OA who have received a single-dose intra-articular HA injection.

Our study was conducted at the Physical Medicine and Rehabilitation Clinic of Fatih Sultan Mehmet Training and Research Hospital between 2023 and 2025, involving a retrospective review of medical records of patients diagnosed with symptomatic knee osteoarthritis (OA) who were followed up in our outpatient clinics and received a single dose of intra-articular hyaluronic acid (HA) injection (Re-Cross by Reviscon - 4.0 ml, 88 mg sodium hyaluronate).

Our single-center, retrospective study plans to enroll at least 133 knees (Kellgren-Lawrence stages 2-3) with knee OA-related pain that have received HA treatment. Patients included in the study were evaluated before the injection, 30 minutes after the injection, and at 1, 3, 6, and 12 months post-injection. Pre-injection assessments, the injection procedure, and all post-injection evaluations were performed by a physician specializing in physical medicine and rehabilitation.

Patients were assessed for pain, stiffness, and function before injection and at 1, 3, 6, and 12 months post-injection using the Visual Analog Scale (VAS) and the Western Ontario and McMaster Universities Arthritis Index (WOMAC) questionnaire. Quality of life was also assessed using the Patient General Assessment (PGA) test scores. In the first post-injection assessment, pain intensity was evaluated using the VAS.

Inclusion Criteria:

• Participants who have provided written informed consent.
• Male and female participants aged 40 to 70.
• Bilateral or unilateral, painful, primary knee osteoarthritis.
• Knee pain lasting at least 4 weeks while standing, walking, and/or moving, and the presence of at least one of the following features on an X-ray taken within the last 3 months: tibiofemoral osteophytes, femoral or tibial endplate osteosclerosis, or narrowing of the joint space (Kellgren-Lawrence grade 2-3).
• Baseline Western Ontario and McMaster Universities Arthritis Index (WOMAC) Pain Score (sum of five 100-mm components) between 200 and 400 mm.
• Individuals deemed by the investigator to be able to adhere to the visit schedule.
• Discontinuation of all NSAIDs, corticosteroids, and other pain relievers, including over-the-counter medications, herbal treatments, or chondroprotective agents prior to injection, and no use of these during the study follow-up period (except for acetaminophen).
• Patients who have not received another intra-articular injection in the knee or participated in a physical therapy program during the follow-up period.

Exclusion Criteria:

• Participants hospitalized in the hospital.
• Participants with inflammatory knee conditions other than OA (e.g., rheumatoid arthritis, chronic hemochromatosis, sickle cell anemia, and/or chondrocalcinosis, as well as arthropathies associated with systemic diseases such as gout and hemophilia, and infectious joint disease).

The presence of significant joint effusion identified by the investigator during a clinical examination and confirmed by an ultrasound examination performed on each patient to determine the presence of effusion

• Body mass index (BMI) >35 kg/m²
• Severe misalignment of the knee axis (i.e., >12° severe varus or valgus deformity and/or clinically significant moderate to severe instability).
• Clinical findings of hip osteoarthritis (OA) and/or hip joint replacement on the same side as the affected knee. Hip joint replacement on the opposite side of the affected knee is not exclusionary, provided the patient does not have symptomatic hip OA.
• Surgical intervention on the symptomatic knee within the previous 12 months (including joint replacement) or arthroscopy of the symptomatic knee within the past 3 months (note: joint replacement of the contralateral knee is permitted if performed more than 12 months prior and the participant does not report pain of ≥ 20 mm on the WOMAC pain subscale).
• Intra-articular (IA) injections in both knees within the past 4 weeks (e.g., corticosteroids, chondroprotective agents).
• Changes to current medications or the addition of new medications to treat knee OA within the past 4 weeks (i.e., a change in dose or regimen lasting at least 4 weeks).
• Regular use of opioid pain relievers for pain management. Use of long-acting pain relievers such as analgesic patches, methadone, and levorphanol at any time