RCT Evidence: Hyaluronic Acid Injections Improve Quality of Life in Knee and Shoulder Osteoarthritis

Key Findings

Randomized controlled trials (RCTs) provide robust evidence that viscosupplementation (hyaluronic acid injections) improves quality of life, physical function, and pain relief:

Knee OA: Multiple large meta-analyses (10,000+ patients) show significant improvements in pain scores, function, and quality of life measures
Shoulder OA: Emerging evidence demonstrates similar benefits for glenohumeral osteoarthritis
Duration: Benefits typically sustained 6-12 months with minimal adverse events
Best Candidates: Early-stage OA patients (Kellgren-Lawrence Grade 1-2) show the most pronounced improvements

Introduction

When evaluating any medical treatment, the gold standard of evidence comes from randomized controlled trials (RCTs). For hyaluronic acid (HA) knee injections—also known as viscosupplementation—a substantial body of RCT evidence now exists demonstrating meaningful improvements in patient quality of life.

This article summarizes the key RCT findings for both knee and shoulder osteoarthritis, providing the evidence base that supports continued coverage and clinical use of this treatment.

Knee Osteoarthritis: RCT Evidence

Large-Scale Meta-Analyses

The most comprehensive evidence comes from systematic reviews pooling data across multiple RCTs:

2025 Network Meta-Analysis

71 RCTs | 10,590 patients

A landmark systematic review and meta-analysis published in 2025 analyzed 71 randomized controlled trials encompassing 10,590 patients. The analysis found that HA injections led to significant improvements in pain and clinical scores related to function and quality of life, particularly for patients with early-stage osteoarthritis.^[1]

BMJ 2022 Systematic Review

24 large placebo-controlled trials | 8,997 patients

This rigorous BMJ systematic review of 24 large placebo-controlled trials found a statistically significant reduction in pain and functional improvement following viscosupplementation. While the magnitude of effect was modest, quality of life benefits were documented across multiple measures.^[2]

Prospective Observational Studies

52-Week Synvisc-One Study (2022)

50 knee OA patients | 1-year follow-up

A prospective observational study tracked 50 knee OA patients receiving Synvisc-One® injections for a full year. Results showed:^[3]

Outcome Measure	Result
Pain (VAS)	Significant decrease
Physical Function (WOMAC)	Significant improvement
Quality of Life (SF-36)	Significant improvement
Duration	Benefits sustained to 52 weeks
Best Responders	Early-stage OA (KL Grade 1)

Key Opinion Leader Reviews

A 2018 comprehensive review in the Journal of Managed Care & Specialty Pharmacy summarized evidence from numerous RCTs, concluding that HA injections consistently reduce knee pain and stiffness while improving quality of life measures for up to 6 months post-injection.^[4]

Shoulder Osteoarthritis: Emerging Evidence

While knee OA has the most extensive evidence base, research increasingly supports HA injections for glenohumeral (shoulder) osteoarthritis.

Systematic Reviews and Meta-Analyses

2023 Glenohumeral OA Meta-Analysis

A systematic review and meta-analysis of RCTs for shoulder osteoarthritis reported:^[5]

Significant improvements in shoulder pain (measured by VAS)
Improved shoulder function on validated scales
Quality of life improvements (SF-36)
No serious adverse events noted

Individual RCT Findings

Study	Outcomes	Duration
Sodium Hyaluronate RCT^[6]	Significant improvement in Oxford Shoulder Score and QoL	6 months
HA vs Placebo RCTs^[7]	Decreased pain, improved ROM, subjective satisfaction	12 weeks
HA vs Corticosteroid Comparison^[8]	HA showed longer-term pain relief and functional improvement	Extended follow-up

Corticosteroid Comparisons

Studies comparing HA to corticosteroid injections for shoulder OA have demonstrated HA’s advantage for longer-term pain relief and sustained functional improvement, supporting improved quality of life beyond what corticosteroids provide.^[8,9]

Summary of Evidence

What the RCTs Show

Knee Osteoarthritis: RCTs robustly support that viscosupplementation improves quality of life, physical function, and pain, especially in early stages of disease

Shoulder Osteoarthritis: Evidence is emerging and growing for similar benefits, including significant improvements in pain, function, and overall QoL measures

Duration of Effect: Benefits are generally sustained from weeks to 6 months, sometimes longer

Safety Profile: Minimal adverse events across all studies

Clinical Implications

This body of RCT evidence has important implications for clinical practice and coverage policy:

For Patients

HA injections offer a proven, low-risk option for improving daily function and quality of life
Early-stage OA patients may see the most benefit
Effects can last 6-12 months, reducing need for daily pain medications

For Clinicians

RCT evidence supports HA as part of a comprehensive OA management strategy
Patient selection matters—early to moderate OA responds best
Imaging guidance can improve injection accuracy and outcomes

For Payers

Coverage decisions should reflect the substantial RCT evidence base
Cost-effectiveness improves when HA delays or prevents surgical intervention
Denial of coverage contradicts peer-reviewed evidence

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References

Network meta-analysis of 71 RCTs (10,590 patients). Scientific Reports, 2025. PMID: 40603830
Pereira TV, et al. Viscosupplementation for knee osteoarthritis: systematic review and meta-analysis. BMJ, 2022;378:e069722. Full Text
Prospective observational study of Synvisc-One® (52-week follow-up). PMC, 2022. PMCID: PMC8924687
Viscosupplementation in osteoarthritis: Key opinion leader review. Journal of Managed Care & Specialty Pharmacy, 2018. Full Text
Efficacy of intra-articular injections of hyaluronic acid in patients with glenohumeral joint osteoarthritis: systematic review and meta-analysis. Wiley Online Library, 2023. Full Text
Sodium hyaluronate injection RCT for shoulder OA. PMCID: PMC11355087
Intra-articular HA for shoulder OA: Range of motion and satisfaction outcomes. PMCID: PMC6464619
Corticosteroid vs HA comparison for shoulder OA. ScienceDirect, 2017. Full Text
Long-term outcomes of shoulder injections. Anesthesia & Analgesia, 2025. Full Text

Additional Resources

CMS Local Coverage Determination L39260: Medicare Coverage Database
Comprehensive Review of Viscosupplementation: Orthopedic Reviews
American Academy of Family Physicians Overview: AAFP
NCBI StatPearls: Viscosupplementation: NBK602915

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