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Single-Injection vs. Multi-Injection HA Products: Which Is Better for Knee OA?

Compare single-injection HA products (Synvisc-One, Monovisc, Durolane) with multi-injection series (Euflexxa, Supartz, Hyalgan) for knee osteoarthritis. Understand the differences and which might work best for you.

By Joint Pain Authority Team

Single-Injection vs. Multi-Injection HA Products: Which Is Better for Knee OA?

Quick Summary

FactorSingle-InjectionMulti-Injection Series
Office visits13-5 (weekly)
ConvenienceHighLower
Total HA delivered6 mL typical6-10 mL typical
EfficacySimilarSimilar
Duration of relief~6 months~6 months
Common productsSynvisc-One, Monovisc, Durolane, Gel-OneEuflexxa, Supartz FX, Hyalgan, Orthovisc

Bottom line: Research shows similar outcomes. Choice often depends on scheduling, insurance, and personal preference.


Understanding Your Options

When your doctor recommends hyaluronic acid (HA) injections for knee osteoarthritis, one of the first decisions is whether to use a single-injection product or a multi-injection series.

Both approaches work by restoring lubrication and cushioning to your knee joint. The main differences are in how the treatment is delivered.


Single-Injection Products

How They Work

Single-injection HA products deliver a larger dose in one visit—typically 6 mL of hyaluronic acid. This is possible because these products are usually cross-linked or highly concentrated, allowing them to provide sustained effect from a single administration.

Available Products

ProductVolumeMolecular WeightSource
Synvisc-One6 mLHigh (6M Da)Avian
Monovisc4 mLHighAvian
Durolane3 mLMedium-HighBacterial
Gel-One3 mLHighAvian

Advantages

One appointment - Complete treatment in a single visit
One copay - Potentially lower out-of-pocket costs
Schedule-friendly - Easier for busy patients or those who travel
No treatment interruption risk - Can’t miss a follow-up injection
Immediate completion - Know you’ve received the full treatment

Considerations

Larger volume at once - May cause more initial swelling
Most are avian-derived - Not suitable for egg/chicken allergies (except Durolane)
Higher upfront product cost - Though total treatment cost is often similar

Multi-Injection Series Products

How They Work

Multi-injection products deliver smaller doses over multiple weekly appointments—typically 2-2.5 mL per injection over 3-5 weeks. This provides a more gradual delivery of HA to the joint.

Available Products

ProductInjectionsVolume EachTotal VolumeSource
Euflexxa3 weekly2 mL6 mLBacterial
Supartz FX3-5 weekly2.5 mL7.5-12.5 mLAvian
Hyalgan3-5 weekly2 mL6-10 mLAvian
Orthovisc3-4 weekly2 mL6-8 mLAvian

Advantages

Smaller injection volume - May be more comfortable per injection
Gradual delivery - HA introduced over time rather than all at once
Non-avian option available - Euflexxa for patients with allergies
Provider monitoring - Multiple visits allow for progress checks
Higher total dose option - 5-injection products deliver more HA overall

Considerations

Multiple appointments - 3-5 weekly visits required
Multiple copays - May increase out-of-pocket costs
Scheduling commitment - Must return weekly for 3-5 weeks
Incomplete series risk - Missing appointments may affect results

Does One Work Better Than the Other?

What the Research Says

Clinical studies comparing single-injection and multi-injection HA products have found:

Key Findings:

  • Similar efficacy in pain reduction and functional improvement
  • Comparable duration of effect (~6 months)
  • No consistent winner in head-to-head trials
  • Individual response varies - some patients do better with one than the other

Why No Clear Winner?

Several factors explain why both approaches work similarly:

  1. Total HA delivered is roughly equivalent
  2. Mechanism of action is the same (joint lubrication)
  3. Disease modification - neither regenerates cartilage
  4. Patient factors matter more than product factors

Cost Comparison

Insurance Perspective

Typical Medicare Scenario:

FactorSingle-Injection3-Injection Series
Product costHigher per unitLower per unit
Office visits13
Injection fees13
Facility fees13
Total costOften similarOften similar

Out-of-Pocket Impact

For patients with copays:

  • Single injection: One copay (e.g., $50-150)
  • Three injections: Three copays (e.g., 3 × $20-50 = $60-150)

The totals often end up comparable, but structure varies by insurance plan.


Making Your Choice

Consider Single-Injection If:

You have a busy schedule or travel frequently
Minimizing appointments is a priority
You have no avian allergies (or can use Durolane)
You want certainty of completing the full treatment
Your provider recommends it based on their experience

Consider Multi-Injection Series If:

You have egg or poultry allergies (choose Euflexxa)
You prefer smaller injection volumes per visit
You can easily attend weekly appointments
You value multiple check-ins with your provider
Your insurance covers more of the multi-injection products

Questions to Ask Your Doctor

  1. What products do you typically use? (Providers often have preferences based on experience)
  2. Is there a coverage difference with my insurance?
  3. Do I have any allergies that limit my options?
  4. How many appointments would each approach require?
  5. Have you seen different results with different products?

Special Situations

If You Need Both Knees Treated

  • Single-injection: Can potentially do both knees in one visit
  • Multi-injection: May require 3-5 visits per knee (though some providers do both same day)

If You’ve Tried One Type Before

If you responded well to a multi-injection series, you might consider:

  • Staying with that approach
  • Trying a single-injection for convenience
  • The opposite is also true—poor response to one type doesn’t mean the other won’t work

If You’re New to HA Injections

Many providers start with whatever they have the most experience with. Trust their recommendation—the difference in efficacy between products is minimal.


The Bottom Line

Both Approaches Work

Research consistently shows similar outcomes between single-injection and multi-injection HA products:

  • Efficacy: Comparable pain relief and function improvement
  • Duration: Both provide ~6 months of relief
  • Safety: Both have excellent safety profiles

Your choice should be based on:

  • Scheduling constraints
  • Insurance coverage
  • Allergy status
  • Personal preference
  • Your provider’s recommendation

Don’t overthink it - the best HA product is one that fits your life and that you’ll follow through with.

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References

  1. Comparison of single vs multiple injection viscosupplementation. PMC. PMC8567800

  2. Comprehensive review of HA products for knee OA. Orthopedic Reviews. Full Text

  3. NCBI StatPearls: Viscosupplementation. NBK602915

  4. CMS LCD L39529. Medicare Coverage Database

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