Understanding the Difference
When your doctor recommends gel injections (viscosupplementation) for knee osteoarthritis, you will likely need to choose between two main types: single-injection products and multi-injection series.
Both types contain hyaluronic acid (HA), a natural substance that lubricates and cushions your knee joint. The key difference is how the treatment is delivered.
Here is the good news: Research shows both approaches work equally well for most patients. The choice often comes down to your schedule, insurance coverage, and personal preference.
Single-Injection Products
Single-injection gel products are designed to give you the complete treatment in one visit. These products use special formulations that deliver a higher concentration of hyaluronic acid at once.
Popular Single-Injection Brands
| Brand | Manufacturer | Volume | Source | FDA Approved |
|---|---|---|---|---|
| Synvisc-One | Sanofi | 6 mL | Avian (chicken) | 2009 |
| Monovisc | DePuy Synthes (J&J) | 4 mL | Avian (chicken) | 2012 |
| Durolane | Bioventus | 3 mL | Non-avian (bacterial) | 2017 |
| Gel-One | Zimmer | 3 mL | Avian (chicken) | 2011 |
How Single Injections Work
Your doctor injects the full dose of hyaluronic acid directly into your knee joint during a single office visit. The gel immediately begins working to:
- Restore lubrication in the joint
- Provide cushioning between bones
- Reduce friction during movement
- Potentially reduce inflammation
The effects typically last 6 months, though some patients experience relief for up to 12 months.
Pros of Single-Injection Products
Cons of Single-Injection Products
Multi-Injection Series
Multi-injection series spread your treatment across several weekly office visits. Each injection adds to the therapeutic effect, building up the hyaluronic acid in your joint over time.
Popular Multi-Injection Brands
| Brand | Manufacturer | Injections | Volume Each | Source | FDA Approved |
|---|---|---|---|---|---|
| Euflexxa | Ferring | 3 | 2 mL | Non-avian (bacterial) | 2004 |
| Supartz FX | Bioventus | 5 | 2.5 mL | Avian (chicken) | 2001 |
| Hyalgan | Fidia | 5 | 2 mL | Avian (chicken) | 1997 |
| Orthovisc | DePuy Synthes | 3-4 | 2 mL | Avian (chicken) | 2004 |
How Multi-Injection Series Work
You visit your doctor once a week for 3 to 5 weeks, depending on the product. At each visit, you receive one injection. The treatment works by:
- Gradually building hyaluronic acid levels in your joint
- Allowing your body time to adjust to each dose
- Spreading the total volume over multiple sessions
- Giving you and your doctor time to monitor your response
After completing the series, the effects typically last 6 months. Some patients repeat the series twice per year for ongoing relief.
Pros of Multi-Injection Series
Cons of Multi-Injection Series
Head-to-Head Comparison Table
| Factor | Single-Injection | Multi-Injection Series |
|---|---|---|
| Office visits | 1 | 3-5 |
| Time to complete treatment | 1 day | 3-5 weeks |
| Total gel volume | 3-6 mL | 6-12.5 mL |
| Copays | 1 | 3-5 |
| Convenience | High | Lower |
| Ability to stop early | Not possible | Yes |
| Infection risk | Lower | Slightly higher |
| Non-avian options | Durolane | Euflexxa |
| Time to feel results | 2-4 weeks | 4-6 weeks after series completion |
| Duration of relief | 6 months average | 6 months average |
| Clinical effectiveness | Comparable | Comparable |
What Does the Research Say?
This is perhaps the most important question: Does one approach work better than the other?
The short answer is no. Multiple clinical studies have compared single-injection and multi-injection products, and the results are clear.
Key Research Findings
Studies show equivalent effectiveness:
- A 2015 meta-analysis in the Annals of Internal Medicine found no significant difference in pain relief between single and multi-injection products
- A 2016 review in Osteoarthritis and Cartilage concluded that all FDA-approved HA products provide similar benefits
- Head-to-head trials comparing Synvisc-One (single) to Hyalgan (5-injection series) found comparable outcomes at 6 months
What the research tells us:
The number of injections does not predict how well the treatment will work. Both approaches restore hyaluronic acid to your joint and provide similar levels of pain relief and improved function.
Why Similar Results?
The science makes sense when you understand how these products work:
- Total dose matters more than delivery schedule - Whether delivered in one shot or five, the goal is restoring adequate hyaluronic acid levels in your joint
- The joint does not “care” how the HA got there - Once the gel is in your knee, it provides the same lubricating and cushioning effects
- Individual response varies - Some patients respond better to one type, but this cannot be predicted in advance
Cost Comparison
Cost is often a deciding factor when choosing between single and multi-injection products. Here is what to expect.
Self-Pay Costs (Without Insurance)
| Product Type | Cost Range | Notes |
|---|---|---|
| Single-injection | $800-$1,500 | Higher per-unit cost, but only one visit |
| Multi-injection series | $600-$1,200 total | Lower per-injection, but 3-5 visits |
With Medicare Coverage
| Product Type | Typical Patient Cost | Notes |
|---|---|---|
| Single-injection | $100-$350 | One 20% copay |
| Multi-injection series | $150-$500 total | Multiple 20% copays |
Hidden Cost Factors
When comparing costs, consider these often-overlooked expenses:
Insurance Coverage Considerations
Both single-injection and multi-injection products are covered by Medicare and most private insurance plans. However, coverage details can differ.
Medicare Coverage
Medicare Part B covers viscosupplementation for knee osteoarthritis when:
- You have a documented diagnosis of knee OA
- You have tried and failed conservative treatments (medications, physical therapy)
- Your doctor documents medical necessity
Both single and multi-injection products are covered equally by Medicare.
Private Insurance Variations
Some private insurers have preferences:
Check Your Coverage First
Before your appointment, call your insurance company or ask your doctor’s office to verify which products are covered and what your out-of-pocket costs will be. Coverage can vary significantly between plans.
Which Is Right for You?
Since both approaches work equally well, your choice should be based on practical factors. Use this decision framework to help you decide.
Choose Single-Injection If:
Choose Multi-Injection Series If:
Questions to Ask Your Doctor
- Which products does my insurance cover best?
- Do you have experience with both single and multi-injection products?
- Based on my schedule and lifestyle, which would you recommend?
- If I have poultry allergies, which non-avian options are available?
- What should I expect in terms of side effects with each approach?
Frequently Asked Questions
Does the number of injections affect how well the treatment works?
No. Research consistently shows that single-injection and multi-injection products provide similar levels of pain relief and improved function. The total dose of hyaluronic acid matters more than how it is delivered.
Can I switch between single and multi-injection products?
Yes. If you have tried one approach and want to try the other, you can switch for your next treatment cycle (usually after 6 months). Your doctor can help you decide if switching makes sense.
Are single-injection products safe?
Yes. All FDA-approved gel injection products have been thoroughly tested for safety. Single-injection products deliver a larger volume at once, which may cause slightly more temporary swelling, but this typically resolves within a day or two.
Do I need imaging guidance for these injections?
Imaging guidance (fluoroscopy or ultrasound) improves accuracy for all knee injections. Studies show that blind injections miss the joint space up to 30% of the time. Ask your provider if they use imaging guidance.
How long do I have to wait between series?
Most doctors recommend waiting at least 6 months between treatment cycles, whether you use single or multi-injection products. Some patients can go longer between treatments if they continue to feel good.
What if I have egg or poultry allergies?
Choose a non-avian product. For single injections, Durolane is made from bacterial fermentation and is safe for patients with poultry allergies. For multi-injection series, Euflexxa is the main non-avian option.
Which approach do most patients choose?
This varies by region and insurance. Single-injection products have grown in popularity due to convenience, but multi-injection series remain common, especially when insurance prefers them or when patients want the gradual approach.
Can I get both knees treated at the same time?
Yes, many patients treat both knees during the same visit or series. Your doctor will advise based on your specific situation and insurance coverage.
The Bottom Line
Both Approaches Work Equally Well
When it comes to single-injection vs multi-injection gel treatments, the research is clear: both provide similar pain relief and functional improvement.
Your decision should be based on:
- Convenience - How many appointments can you realistically make?
- Insurance - Which products does your plan cover best?
- Allergies - Do you need a non-avian option?
- Personal preference - Do you prefer one-and-done or gradual treatment?
Talk to your doctor about which approach fits your life. Either way, you are choosing a proven treatment that can provide 6 months or more of relief from knee osteoarthritis pain.
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Questions? Browse our guides:
How to Choose a ProviderRelated Resources
- All Gel Injection Brands Compared
- Hyaluronic Acid Injections: Complete Guide
- Synvisc-One vs. Monovisc
- Euflexxa vs. Durolane
- Medicare Coverage for Gel Injections
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