Knee osteoarthritis is one of the most common problems I treat, and patients are increasingly interested in options that fall somewhere between medications and joint replacement.
Cortisone injections, hyaluronic acid, physical therapy, anti-inflammatory medications, PRP, laser therapy, red light therapy, TENS, and shockwave treatment are all frequently discussed. But another technology that has received growing attention is therapeutic ultrasound, particularly long-duration, wearable ultrasound that can be used at home.
In Episode 44 of The Joint Replacement Podcast, I sat down with George Lewis, PhD, CEO of ZetrOZ Systems, to discuss the science behind Sustained Acoustic Medicine, or SAM, and where therapeutic ultrasound may fit into the treatment of knee osteoarthritis.
One important disclosure: I serve as a paid physician consultant and key opinion leader for ZetrOZ Systems. That financial relationship is important for readers and listeners to know when considering my discussion of this technology.
Diagnostic Ultrasound and Therapeutic Ultrasound Are Not the Same Thing
Most patients are familiar with ultrasound as an imaging technology. Diagnostic ultrasound uses sound waves and the echoes produced by tissues to create an image.
Therapeutic ultrasound uses the same general form of mechanical energy differently. Instead of creating an image, ultrasonic energy is delivered to tissue with the goal of producing biological effects.
In our conversation, Lewis described potential thermal, mechanical, circulatory, and cellular effects of therapeutic ultrasound. The concept itself is not new. Therapeutic ultrasound has been used in rehabilitation medicine for decades.
What is different about SAM is primarily the dose and duration of treatment.
Traditional therapeutic ultrasound might be administered by a physical therapist for several minutes during an office visit. Wearable long-duration ultrasound is instead designed to deliver relatively low-intensity ultrasound for several hours while a patient is at home. In one randomized study of knee osteoarthritis, treatment was delivered for four hours per day for six weeks. PubMed
Does Therapeutic Ultrasound Actually Work for Knee Arthritis?
This is the question that matters most.
The evidence should be separated into two categories:
1. Therapeutic ultrasound in general
A 2024 systematic review and meta-analysis examined 21 randomized controlled trials involving 1,315 patients with knee osteoarthritis. Therapeutic ultrasound was associated with statistically significant improvements in both pain and WOMAC measures of function compared with controls.
Importantly, there was considerable heterogeneity among studies. Different investigators used different ultrasound intensities, frequencies, treatment durations, and protocols. That makes it difficult to assume that every ultrasound device or treatment regimen will produce the same effect. PubMed
Earlier systematic reviews have also reported improvements in pain and function with therapeutic ultrasound, although study quality and treatment protocols have varied considerably. PubMed
2. Long-duration wearable ultrasound
A randomized, double-blind, placebo-controlled trial specifically examined long-duration low-intensity ultrasound in 90 patients with radiographically confirmed knee osteoarthritis.
Patients receiving active therapy used the device for four hours daily for six weeks. The active-treatment group experienced an average pain reduction of 1.96 points compared with 0.85 points in the placebo group, along with significantly greater improvement in functional scores. PubMed
Those findings are encouraging, but they should also be put into perspective. This was a relatively small trial, and larger independent studies with longer follow-up would strengthen our understanding of the magnitude and durability of the benefit.
Can Ultrasound Regrow Knee Cartilage?
This may be the most important distinction we made during the episode.
Patients understandably want to know whether any nonsurgical technology can actually reverse arthritis.
At this point, we should not tell patients that therapeutic ultrasound has been proven to regrow human articular cartilage.
Lewis discussed laboratory and animal research evaluating cartilage and chondroprotective effects, but he appropriately distinguished that research from evidence in humans.
I think the better framework is:
joint preservation rather than joint regeneration.
A therapy can potentially improve pain or function without recreating normal cartilage.
That distinction applies to many arthritis treatments. A patient feeling better does not necessarily mean that an X-ray will suddenly demonstrate restoration of previously lost joint space.
Who Might Be the Best Candidate?
One of the more interesting parts of our conversation involved timing.
Lewis believes the most compelling application may be patients with mild to moderate osteoarthritis, when meaningful cartilage and joint space remain.
That makes intuitive sense from a joint-preservation perspective.
Once a knee has severe deformity, major mechanical dysfunction, or end-stage bone-on-bone arthritis, no external ultrasound device is going to recreate the normal structure of the knee.
That does not necessarily mean that someone with advanced arthritis cannot experience symptomatic improvement. It does mean that the expectations should be different.
For an earlier-stage patient, the goal might be long-term conservative management.
For someone approaching joint replacement, the goal may simply be symptom control or delaying surgery for a period of time.
How Is This Different From TENS, Laser, or Red Light Therapy?
One reason I wanted to have this conversation is that patients are now exposed to an enormous number of devices marketed for joint pain.
They often get grouped together despite very different mechanisms.
TENS primarily uses electrical stimulation to influence pain signaling.
Photobiomodulation or red light therapy uses light energy.
Laser therapy uses another form of electromagnetic energy with treatment parameters that vary substantially among devices.
Shockwave therapy involves acoustic pressure waves and is commonly discussed for certain tendon and soft-tissue disorders.
Therapeutic ultrasound uses high-frequency mechanical sound waves.
Simply calling all of these treatments “noninvasive” does not make them equivalent. Each technology needs to be evaluated based on its mechanism, dose, indication, and—most importantly—its clinical evidence.
What About Cortisone, Gel Injections, or PRP?
I do not think patients should view this as an either/or decision.
Knee arthritis treatment is rarely a single intervention.
Depending on the patient, nonsurgical management can include:
exercise
weight optimization
activity modification
physical therapy
anti-inflammatory medications when appropriate
injections
bracing
and potentially device-based treatments
The appeal of therapeutic ultrasound is that it offers a local, noninvasive and noninjectable option.
That may be particularly attractive to patients who do not want repeated injections or cannot comfortably use certain systemic medications.
However, we should avoid concluding from current evidence that therapeutic ultrasound has definitively been shown to outperform all injections, PRP, or every other nonsurgical arthritis treatment. Head-to-head comparative evidence remains much more limited.
Is SAM FDA Cleared?
Yes.
The FDA lists ZetrOZ’s long-duration ultrasound technology as a Class II ultrasonic diathermy device. The currently cleared SAM 3.0 indications include home use for deep heating of tissues for conditions including relief of pain, muscle spasm, joint contractures, local increases in circulation, and pain associated with limited mobility and function related to soft-tissue conditions including knee osteoarthritis. FDA Access Data
It is worth emphasizing an important distinction:
FDA clearance does not mean that a device has been proven to cure osteoarthritis or regenerate cartilage.
Those are separate scientific questions that require clinical evidence.
What About Combining Ultrasound With Medication?
Another area of research involves sonophoresis, using ultrasound in combination with a topical medication to potentially enhance local delivery.
A small multicenter study involving 32 patients evaluated sustained acoustic medicine combined with topical 1% diclofenac for knee osteoarthritis. Investigators reported improvements in pain and WOMAC function over seven days, with no study-related adverse events.
Because that study combined ultrasound with diclofenac and did not include the same type of placebo-controlled comparison as the larger randomized trial, it cannot tell us how much of the improvement came independently from ultrasound versus the medication or their combination. PubMed
That is an interesting research direction, but one that still deserves larger controlled trials.
What Are the Risks?
Therapeutic ultrasound is non-ionizing. It does not expose patients to ionizing radiation like an X-ray.
Published randomized trials and systematic reviews have generally reported relatively few significant treatment-related adverse events. The 2024 meta-analysis of therapeutic ultrasound for knee osteoarthritis reported no ultrasound-related adverse events in the included studies. PubMed
With wearable systems, practical issues such as skin sensitivity to adhesive patches can also become relevant because treatment is repeatedly applied to the same region.
As with any medical device, appropriate patient selection, correct placement, adherence to the manufacturer’s instructions, and clinician oversight matter.
Could Technologies Like This Delay Knee Replacement?
Possibly—but this is where we need to be precise.
If a nonsurgical treatment meaningfully reduces pain and maintains function, a patient may be able to postpone joint replacement.
That is different from proving that the therapy changes the natural history of osteoarthritis or prevents eventual knee replacement.
To establish true disease modification, we would want prospective trials demonstrating outcomes such as slower structural progression, less cartilage loss, or lower rates of subsequent surgery over many years.
Those data are not yet sufficient to make that claim.
For me, that is one of the most interesting unanswered questions.
My Takeaway
Therapeutic ultrasound occupies an interesting space in osteoarthritis care.
There is randomized clinical evidence and meta-analytic evidence suggesting that therapeutic ultrasound can improve pain and function in knee osteoarthritis. Long-duration wearable ultrasound has also demonstrated benefit compared with placebo in a randomized trial. PubMed
At the same time, I think we need to resist overstating what the evidence demonstrates.
We do not currently have convincing human evidence that therapeutic ultrasound regenerates a severely arthritic knee or eliminates the eventual need for joint replacement.
Instead, I think the more appropriate question is:
Can we improve the environment of an arthritic joint, reduce symptoms, maintain function, and potentially help selected patients preserve their native knee longer?
That is a much more scientifically defensible—and clinically interesting—question.
And it is exactly the conversation I wanted to have with George Lewis.
Watch or listen to Episode 44 of The Joint Replacement Podcast: “Can Ultrasound Treat Knee Arthritis Without Injections?” featuring George Lewis, PhD, CEO of ZetrOZ Systems.
References
- Luo Y, Rahmati M, Kazemi A, et al. Effects of therapeutic ultrasound in patients with knee osteoarthritis: a systematic review and meta-analysis. Heliyon. 2024;10(10):e30874. doi:10.1016/j.heliyon.2024.e30874. PubMed
- Draper DO, Klyve D, Ortiz R, et al. Effect of low-intensity long-duration ultrasound on the symptomatic relief of knee osteoarthritis: a randomized, placebo-controlled double-blind study. J Orthop Surg Res. 2018;13:257. PubMed
- Zhang C, Xie Y, Luo X, et al. Effects of therapeutic ultrasound on pain, physical functions and safety outcomes in patients with knee osteoarthritis: a systematic review and meta-analysis. Clin Rehabil. 2016;30(10):960-971. PubMed
- Madzia A, et al. Sustained Acoustic Medicine combined with a diclofenac ultrasound coupling patch for the rapid symptomatic relief of knee osteoarthritis: multi-site clinical efficacy study. 2021. PubMed
- U.S. Food and Drug Administration. 510(k) Summary: SAM 3.0 Multi-Hour Continuous Ultrasound Device, K260076. 2026. FDA Access Data
Disclosure: Dr. Matthew Sloan serves as a paid physician consultant and key opinion leader for ZetrOZ Systems.