In this video, we are going to talk about pentosan polysulfate, what this medication is, and how it might be helpful for you if you are dealing with arthritis of your knee, hip, shoulder, or some other joint in your body.

Please understand, in this video, I am not giving you medical advice. This is meant for general information and educational purposes only.

Statistics on osteoarthritis

Osteoarthritis is one of the most common afflictions adults suffer. It affects over 32.5 million U.S. adults, according to the CDC. When you broaden it to other forms of arthritis, like rheumatoid arthritis, over 22 percent of adults in the U.S. have been told by a doctor they have arthritis.

Joint replacement surgeries in the United States

To be expected, the surgery performed to treat osteoarthritis – joint replacement – is becoming more and more common as well. As of 2017, orthopedic surgeons were doing about one million joint replacement surgeries per year. By 2030, 3.5 million total knee arthroplasties are expected to be performed each year.

But that surgery – total hip arthroplasty or total knee arthroplasty – or joint replacement – is not healing the damaged bone and cartilage. It’s replacing it with metal and plastic.

What osteoarthritis is and what it isn’t

The reason we have performed these surgeries for decades now, and that joint replacement specialists say it is the only option – is based on what the conventional theory for osteoarthritis says the disease is. It’s just that – a disease.

The majority of doctors and orthopedic surgeons tell patients osteoarthritis is a wear-and-tear process occurring after a major injury, like a torn ACL, or over a long period of time in someone who places heavy demands on their knees or hips, like runners or people who do manual labor jobs. That wear-and-tear process takes a toll on the articular cartilage in the hip or knee, as well as the bone under it. The analogy doctors use so often is tread on a tire. The tread is the articular cartilage lining on the ends of the bones. When that articular cartilage – the tire tread – gets thinner and thinner, or even has spots where there is exposed bone, the thinking goes that you have to replace it with metal and plastic.

Current treatments for osteoarthritis

Before patients get to the point of needing hip or knee replacements, we try other treatments. The mainstay of treatment for years has been cortisone shots into the knee. These injections don’t fix the underlying problem – the worn out cartilage and bone – but they usually relieve pain. When the pain relief from one shot wears off, a few months later, you get another one. Pretty soon, you get less and less relief from each shot, until you finally give up and get a knee replacement.

The problem with cortisone shots, in addition to not treating the actual damage in the knee and helping it heal, is that there is a lot of scientific evidence now that cortisone does more damage to the knee, especially the more of them you get. It can speed the breakdown of the articular cartilage. In essence, it might make you feel good, but it also might make the arthritis in your knee worse.

Other injections used include viscosupplementation – like Synvisc, Hyalgan, Supartz, and others – have some benefits, in some studies, but they aren’t significantly better. For some people they don’t help much at all.

Some surgeons will offer to scope your knee – or perform what’s called a diagnostic arthroscopy. They go in and clean out the debris and smooth out the damage. Several studies over the last decade have shown those surgeries might have limited benefit at best in the first few months after the procedure, but it is not helpful long-term and might actually be harmful.

And again, all of these treatments for osteoarthritis lead to joint replacement.

But now, there is a treatment proposed that is suggested to be very beneficial for osteoarthritis called pentosan polysulfate.

What is pentosan polysulfate?

Pentosan is an FDA approved medication used to relieve the symptoms like pain and discomfort of interstitial cystitis, or inflammation of the bladder. It’s been used for that purpose for decades. It is sold as an oral medication – a pill you take by mouth – under the brand name Elmiron.

But pentosan has been used as a treatment for arthritis in the veterinary world and by Australian physicians for many years. It has only recently received attention for that purpose here in the U.S. There are clinics here who use pentosan as an off-label treatment for osteoarthritis, where patients inject it under the skin like patients with diabetes do with insulin.

Here are some of the proposed mechanisms of action that might make pentosan effective for osteoarthritis:

To see if this medication might be useful, let’s start by looking at the animal studies, to see if it has any benefit for arthritis, and if so, why it might work.

Studies on pentosan polysulfate

A 1999 review looking at research that studied pentosan polysulfate for osteoarthritis on rats, rabbits, dogs and other animals showed reduced joint swelling, reduced inflammatory markers in the joint fluid, better cartilage integrity and improved proteoglycan synthesis. Based on this scientific literature, the researchers believed pentosan polysulfate should be reclassified as a Structure-modifying osteoarthritis drug.

In a 2012 study, researchers created arthritis in 18 horses. Nine of the horses received pentosan polysulfate, and nine served as controls. The horses that received pentosan polysulfate were found to have significantly less articular cartilage fibrillation, or cartilage breakdown.

A 2019 study of rats with osteoarthritis looked at the expression of biomarkers and inflammatory mediators we see in arthritic joints – interleukin-1β, tumor necrosis factor-α, cartilage oligomeric matrix protein, cathepsin K, and tartrate-resistant acid phosphatase. Not only did pentosan lead to an improvement in symptoms of arthritis, it appeared to downregulate the expression of those harmful biomarkers and inflammatory mediators and cytokines.

Now let’s turn to evidence we have in humans.

Pentosan polysulfate for hip and knee arthritis

Human studies on pentosan polysulfate

In 2005, scientists performed a randomized, double-blind, placebo-controlled study at a medical center in Australia. 114 patients aged 18 or older with osteoarthritis of the knee were randomly assigned to receive pentosan polysulfate as a weekly intramuscular injection for four weeks or a placebo injection of Ringer’s solution to serve as controls. They found significant differences in duration of joint stiffness, pain at rest, and patient global assessment – basically how well they were doing overall – up to five months after the four weeks of injections. The pentosan patients experienced less pain with walking and better overall function with activities of daily living.

In a study published in 2010, 20 patients received weekly subcutaneous injections of pentosan for six weeks. All twenty had reduced joint swelling. They also had improved knee flexion, less pain while walking, and less pain after climbing up and down stairs. These clinical improvements continued for almost one year.

A case study published in 2017 offered insight into how pentosan polysulfate might work in human patients. A 70-year-old woman with osteoarthritis underwent a trial of this medication, injected into her muscle twice weekly for three weeks. Using a Numerical Rating Scale, her pain dropped from an 8 to a 0. An MRI taken two weeks after the treatment showed the bone marrow edema in the femur and tibia of her knee – that was seen on an MRI before treatment – was resolved.

In a 2019 study in the journal PLoS One, researchers determined that pentosan suppresses the release of nerve growth factor in the subchondral bone which likely helps to decrease pain patients experience with knee osteoarthritis.

Anecdotally, Australian researchers say that among professional athletes using the medication, they report experiencing significantly less pain levels while maintaining high levels of activity.

Clinical trial

Earlier, I talked about how physicians who prescribe pentosan polysulfate for patients with osteoarthritis do so by using it as an off-label treatment. That means it is not currently FDA approved for osteoarthritis.

A clinical trial of pentosan polysulfate just started with the NIH, which could be a major step to having it approved by the FDA as a treatment for osteoarthritis. Researchers at Northwestern and out of Australia are doing a triple-blinded, placebo controlled trial involving almost 1000 patients with osteoarthritis, with the treatment group getting twice weekly subcutaneous injections of pentosan polysulfate, and the control group getting saline injections. They will then follow the participants for about 18 months to see if pentosan polysulfate had a significant benefit for osteoarthritis.

Side effects of pentosan polysulfate

Pentosan is a blood thinner, so you want to avoid it if you’re taking other blood thinners, like Coumadin, for a heart condition or other medical problem. You might also want to eliminate using anti-inflammatory medications, like Advil or Aleve, for the same reasons. And maybe, since it is a blood thinner, don’t take it when you are about to undergo surgery.

With Elmiron, or oral pentosan polysulfate, diarrhea, hair loss, nausea, headache, stomach upset, or abdominal pain have been reported. There are also reports that extended use of Elmiron might cause an increased risk of developing pigmentary maculopathy, a type of eye damage. These side effects have not been reported with subcutaneously injected pentosan polysulfate.

Treatment regimen

There aren’t many clinics in the U.S. where physicians and surgeons are using pentosan for osteoarthritis. But generally, pentosan is given as a subcutaneous injection, right under your skin, usually in your abdomen, twice a week for six weeks or longer.

Again, please understand, in this video, I am not giving you medical advice. This is meant for general information and educational purposes only.


From the research currently available, I believe pentosan polysulfate shows promise. It appears to improve or resolve the lesions in the subchondral bone – the layer of bone just below the cartilage in joints. We need much more research, especially the results of the randomized, placebo controlled, blinded study currently underway, to establish if it’s truly effective in treating osteoarthritis. If you are battling hip or knee arthritis, or arthritis of some other joint, you could at least discuss it with your doctor.

Links to studies mentioned in the video

If you would like to read the studies I mentioned in the video, here are links to them:

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I’m Dr. David Geier. Thank you for watching, and I look forward to helping you feel and perform Better Than Ever.