Cross-linked Hyaluronic Acid in Knee Osteoarthritis

Clinical Superiority of Cross-linked Hyaluronic Acid in Knee Osteoarthritis: Sustained Efficacy on Pain and Function

Knee Osteoarthritis (Knee OA) leads to pain and loss of function, especially in recreational athletes. While hyaluronic acid (HA) injections are a common part of conservative treatment, comparative data on the efficacy of straight-chain (ST-HA) versus cross-linked (CL-HA) formulations remain limited. Therefore, the aim of this study was to compare the 6-month efficacy of a single dose of CL-HA versus two doses of ST-HA regarding pain, stiffness, and joint function in recreational athletes aged 50-70 with Kellgren-Lawrence grade 2-3 Knee OA refractory to pharmacological treatment.

Study Overview

• Status: Completed
• Conditions: Knee Osteoarthritis (Knee OA)
• Intervention / Treatment: Drug: Straight-bonded hyaluronic acid; Drug: cross-linked hyaluronic acid

Detailed Description

This retrospective observational study included 88 recreational athletes (CL-HA: n=44, ST-HA: n=44). All participants received either a single dose of CL-HA or two doses of ST-HA administered 4 weeks apart. Patients were comparatively evaluated pre-treatment and at 1, 3, and 6 months post-treatment using the WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) and VAS scores.

• Study Type: Observational
• Enrollment (Actual): 88

Contacts and Locations

Study Locations

• Turkey (Türkiye)
  • Istanbul, Turkey (Türkiye)
    • İstanbul Medipol University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

This retrospective observational study was conducted in a multicenter manner and included recreational athletes aged between 50 and 70 years who applied to Medipol Esenler Hospital and Republic of Turkey Ministry of Health Erenköy Physical Therapy and Rehabilitation Hospital due to knee pain and were diagnosed with gonarthrosis between January 2021 and December 2024.

Description

Inclusion Criteria: Inclusion criteria: Recreational athletes aged 50-70 years; participants must not have received any injections or undergone physical therapy or rehabilitation in the last 3 months; and symptomatic cases of Kellgren-Lawrence stage 2-3 knee osteoarthritis and failure of pharmacological treatment.

Exclusion Criteria: Inflammatory disease, active rheumatic disease, malignancy, bleeding diathesis, peripheral neuropathy, BMI >30, grade 4 gonarthrosis, regular NSAID use, previous knee surgery, local infection at the procedure site, corticosteroid injection at the procedure site within the last 3 months, systemic corticosteroid use within the last 2 weeks, immunosuppressant use or immunodeficiency within the last 6 weeks, and any local or systemic osteoarthritis-related treatments (therapeutic exercises, physical therapy, other injections, NSAIDs, etc.) within the last 6 months.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patients were comparatively evaluated pre-treatment and at 1, 3, and 6 months post-treatment using the WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) score.	Minimal value is 0, while maximum value is 96.	Patients were comparatively evaluated pre-treatment and at 1, 3, and 6 months post-treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patients were comparatively evaluated pre-treatment and at 1, 3, and 6 months post-treatment using the VAS score.	Minimal value is 0, while maximum value is 10.	Patients were comparatively evaluated pre-treatment and at 1, 3, and 6 months post-treatment

Collaborators and Investigators

• Sponsor: Istanbul Medipol University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 2, 2021
• Primary Completion (Actual): December 31, 2024
• Study Completion (Actual): May 31, 2025

Study Registration Dates

• First Submitted: November 17, 2025
• First Submitted That Met QC Criteria: November 17, 2025
• First Posted (Actual): November 21, 2025

Study Record Updates

• Last Update Posted (Actual): February 27, 2026
• Last Update Submitted That Met QC Criteria: February 24, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Knee Osteoarthritis, Cross-linked Hyaluronic Acid, Recreational Athletes, Intra-articular Injection, WOMAC
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Arthritis; Joint Diseases; Rheumatic Diseases; Osteoarthritis; Osteoarthritis, Knee
• Other Study ID Numbers: E-10840098-202.3.02-5817

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: After publication in a journal, I will share all IPD that underlie results in a publication
• IPD Sharing Time Frame: Beginning immediately after publicaiton
• IPD Sharing Access Criteria: I will consider review requests for IPD sharing and how they will be reviewed.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No