Comparing Single-Injection HA Leaders
When your doctor recommends a single-injection hyaluronic acid treatment for knee osteoarthritis, two names often come up: Monovisc and Synvisc-One. Both offer the convenience of one-and-done treatment, but they use different formulation strategies.
Understanding these differences can help you have a more informed conversation with your doctor about which option might work better for you.
Side-by-Side Comparison
| Factor | Monovisc | Synvisc-One |
|---|---|---|
| Injections needed | 1 | 1 |
| Molecular weight | High (1-2.9 million Da) | Very high (6 million Da) |
| Cross-linking | No (native HA) | Yes (hylan polymer) |
| Source | Avian (chicken comb) | Avian (chicken comb) |
| Volume | 4 mL | 6 mL |
| Egg allergy safe | No | No |
| FDA approval year | 2014 | 2009 |
| Duration of relief | Up to 6 months | Up to 6 months |
| Medicare covered | Yes | Yes |
| Manufacturer | Anika Therapeutics | Sanofi |
| Years on market | 10+ years | 15+ years |
Monovisc: Non-Cross-Linked Single Injection
What It Is
Monovisc is a high molecular weight, non-cross-linked hyaluronic acid derived from chicken combs. Unlike cross-linked products, it maintains the natural structure of HA while still providing single-injection convenience.
Advantages
Considerations
Best For
- Patients wanting single-injection convenience
- Those preferring non-cross-linked formulation
- Patients concerned about potential reactions to cross-linked products
- Anyone seeking a smaller injection volume
Synvisc-One: The Original Single-Injection HA
What It Is
Synvisc-One contains cross-linked hyaluronic acid (hylan G-F 20 polymer) that creates a gel-like substance with very high molecular weight and viscosity. It was the first single-injection HA product approved in the U.S.
Advantages
Considerations
Best For
- Patients wanting the most established single-injection option
- Those who’ve responded well to Synvisc (original 3-injection) formulation
- Patients preferring very high molecular weight for cushioning
- Anyone whose provider has extensive Synvisc-One experience
The Science: Cross-Linked vs. Non-Cross-Linked
Understanding the Difference
The key difference between these products is the cross-linking process:
Non-Cross-Linked (Monovisc):
- Natural HA molecular structure
- High MW achieved through purification
- More similar to native joint HA
- Potentially less inflammatory
- Easier to inject
Cross-Linked (Synvisc-One):
- Chemically modified HA polymer
- Very high MW from cross-linking
- Creates gel-like substance
- Maximum viscosity and elasticity
- Longer residence time (theoretically)
What Research Shows
Studies comparing cross-linked and non-cross-linked HA products have found:
- Similar clinical outcomes for pain relief and function
- Comparable duration of effect (both ~6 months)
- Slightly higher reaction rates with some cross-linked products (but still rare)
- No consistent superiority of one formulation over the other
- Individual variation - some patients respond better to specific formulations
Key insight: The cross-linking difference is more theoretical than clinical. Both work well for most patients.
Clinical Evidence Face-Off
Monovisc Studies
Clinical trials for Monovisc have demonstrated:
- Significant pain reduction compared to placebo
- Non-inferiority to other single-injection HA products
- Good safety profile with low adverse event rates
- Sustained benefit for up to 6 months post-injection
- Efficacy across different severity levels of knee OA
Synvisc-One Studies
Research on Synvisc-One has shown:
- Extensive clinical data from thousands of patients
- Superior outcomes compared to saline placebo
- Long-term safety confirmed over 15+ years
- Repeat treatment effectiveness - many patients receive multiple series
- Real-world effectiveness matching clinical trial results
Direct Comparisons
Limited head-to-head studies exist, but the available evidence suggests:
- Equivalent pain relief between the two products
- Similar functional improvements
- Comparable safety profiles (with slightly more reactions reported for cross-linked products overall)
- No significant difference in duration of effect
Injection Volume: Does It Matter?
The 4 mL vs. 6 mL Question
Monovisc: 4 mL
- Smaller volume may mean less initial joint distension
- Potentially less swelling immediately post-injection
- Easier for some providers to inject
- Still delivers full therapeutic dose
Synvisc-One: 6 mL
- Larger volume provides maximum gel distribution
- May cause more temporary swelling (typically resolves in 24-48 hours)
- Full 6 mL dose delivers complete hylan polymer amount
- Well-tolerated by most patients
Clinical reality: Most patients tolerate both volumes well. The difference in post-injection swelling is usually minimal and temporary.
Allergies and Contraindications
Important: Both Are Avian-Derived
Monovisc and Synvisc-One are both derived from chicken combs.
If you have allergies to:
- Eggs
- Chicken
- Feathers
- Other poultry products
You should avoid both products and ask your doctor about non-avian alternatives like:
- Durolane (bacterial fermentation, single injection)
- Euflexxa (bacterial fermentation, 3 injections)
- Gel-One (if no avian allergy concern)
Always inform your doctor about any allergies before receiving HA injections.
Insurance and Cost Comparison
Medicare Coverage
Both Monovisc and Synvisc-One are covered by Medicare Part B when medically necessary:
- Documented knee osteoarthritis
- Failed conservative treatment (3+ months typically)
- Meets Local Coverage Determination (LCD) requirements
Cost Breakdown
| Factor | Monovisc | Synvisc-One |
|---|---|---|
| Office visits | 1 | 1 |
| Copays (typical) | 1 × $50-150 | 1 × $50-150 |
| Injection fees | Once | Once |
| Average cost (with insurance) | $100-200 | $100-200 |
| Average cost (without insurance) | $800-1,200 | $1,000-1,500 |
Important: Single-injection products typically have lower total out-of-pocket costs than multi-injection series due to fewer office visit copays.
Provider Experience and Availability
Synvisc-One Advantage
Synvisc-One has been on the market longer, which means:
- More providers have experience using it
- More clinical comfort with administration technique
- Better known to both doctors and patients
- More insurance formularies may preferentially cover it
Monovisc Consideration
While newer, Monovisc:
- Is made by Anika Therapeutics (maker of Orthovisc and other established HA products)
- Has 10+ years of market presence
- Is available through most orthopedic and pain management practices
- May be preferred by some providers who like non-cross-linked formulations
Making Your Decision
Questions to Ask Your Doctor
- Which product do you have more experience administering?
- Do I have any avian allergies that would rule out both?
- Have you noticed patients responding differently to cross-linked vs. non-cross-linked?
- What does my insurance cover better?
- Have I responded well to any HA products in the past?
- Are there any reasons you’d recommend one over the other for my specific case?
Decision Framework
Choose Monovisc if:
- You prefer non-cross-linked formulation
- You want a smaller injection volume (4 mL)
- You’re concerned about potential cross-linking reactions
- Your doctor recommends it based on experience
Choose Synvisc-One if:
- You want the most established single-injection product
- You prefer very high molecular weight formulation
- You’ve had positive results with original Synvisc
- Your doctor has extensive experience with this product
- Your insurance preferentially covers Synvisc-One
The Bottom Line
Both Are Excellent Single-Injection Options
Monovisc and Synvisc-One are both effective single-injection HA treatments:
- Clinical outcomes are very similar
- Duration of relief is comparable (~6 months)
- Both are covered by Medicare and most insurance plans
- Both have good safety profiles
- Both offer one-and-done convenience
The choice often comes down to:
- Your doctor’s experience and preference
- Cross-linked vs. non-cross-linked formulation philosophy
- Injection volume preference (4 mL vs. 6 mL)
- Insurance coverage specifics
- Your individual response (if you’ve tried HA before)
The truth: For most patients, both work equally well. The most important factors are receiving the injection from an experienced provider and following proper post-injection care instructions.
Don’t overthink it - either product can provide significant relief when appropriately indicated.
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How to Choose a ProviderFrequently Asked Questions
Can I try the other one if the first doesn’t work?
Yes. If you don’t get adequate relief from one product, your doctor may recommend trying a different HA formulation. Some patients respond better to specific brands or molecular weights.
Which one has fewer side effects?
Both have similar safety profiles with low rates of adverse reactions. Non-cross-linked products (Monovisc) may theoretically have slightly lower inflammatory reaction rates, but clinically the difference is minimal.
How soon will I feel results?
Most patients notice improvement within 2-4 weeks, with maximum benefit at 8-12 weeks. Results vary by individual.
Can I get a second injection sooner if it doesn’t work?
Medicare and most insurance plans typically cover one series per knee per six months. Your doctor may recommend trying a different product or treatment approach rather than repeating too soon.
Which lasts longer?
Clinical studies show similar duration for both products—typically up to 6 months. Individual results vary based on activity level, OA severity, and other factors.
Is one better for severe arthritis?
Neither has shown clear superiority for severe OA. However, patients with very advanced arthritis (bone-on-bone) may not respond as well to any HA product and might be better candidates for surgical interventions.
References
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Monovisc (high molecular weight sodium hyaluronate) Prescribing Information. Anika Therapeutics.
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Synvisc-One (hylan G-F 20) Prescribing Information. Sanofi.
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Comparative effectiveness of single-injection viscosupplementation. Cartilage. 2020.
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Systematic review of cross-linked vs. non-cross-linked hyaluronic acid. Journal of Orthopaedic Surgery and Research. 2021.
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Real-world effectiveness of single-injection HA products. PM&R. 2019.
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CMS LCD L39529 - Intraarticular Knee Injections. Medicare Coverage Database
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