Prolotherapy for Knee Osteoarthritis

Can a series of sugar-water injections ease knee OA pain? Doctors and researchers have differing opinions about the therapy’s effectiveness and safety.


Most treatments for osteoarthritis (OA) address only symptoms and may create other challenges. Weight loss and exercise programs may be difficult for people to follow successfully. The side effects of pain medications may cause other health problems. Researchers looking for less risky and more accessible, effective options are giving new scrutiny to an older treatment, prolotherapy, for its potential to improve knee OA symptoms.

What is Prolotherapy?

Prolotherapy is injection of an irritant solution (often a form of sugar called dextrose) into joints, ligaments, and tendons. A typical treatment program involves 15 to 20 shots given monthly for three to four months, followed by occasional, as-needed shots.

While the therapy has been in use for 75 years, researchers and doctors still aren’t sure how the shots improve pain and other symptoms. And many remain skeptical it even works at all.

David Rabago, MD, an associate professor of family medicine at the University of Wisconsin-Madison School of Medicine and Public Health, treats some of his patients with prolotherapy. He says one theory is that injecting dextrose at certain concentrations triggers a natural healing process, stimulating repair of damaged tissues. Dr. Rabago and colleagues have authored much of the recent research on prolotherapy for knee OA, including a National Institutes of Health-funded randomized controlled trial published in 2013 in the Annals of Family Medicine.

What Are Studies Showing?

In the randomized controlled trial, Dr. Rabago and his team placed 90 people with knee OA into one of three groups: the first group received prolotherapy, the second received inactive salt-water shots and the third was given a pamphlet of knee exercises to be done at home three times a week.

For the first two groups, doctors injected a solution into the knee joint and in up to 15 surrounding tender areas targeting points of pain and swelling. This procedure was performed on three occasions, four weeks apart (with the possibility of two extra treatments, if needed). The study was "blinded," meaning no one involved knew who got prolotherapy sugar-water versus salt-water injections. Dr. Rabago says his team included the exercise comparison group to rule out the possibility of mistaking a placebo effect (in either injection group) for a true therapeutic response, a problem seen in less well-designed trials.

The researchers used what's known as a WOMAC score to compare participants' levels of pain, stiffness and physical function before treatment and a year after they received their first series of shots or started the exercise program.

The WOMAC score of those who received prolotherapy improved 24 percent, compared with an 11-percent improvement in the salt-water group and a 12-percent improvement in the exercise group. The changes in the prolotherapy group versus the comparison groups were great enough that researchers could rule out the possibility of chance findings. More importantly, says Dr. Rabago, the changes were large enough to make meaningful differences in patients’ daily lives.

Other research on prolotherapy for knee OA has also noted some benefits. A small trial of 13 patients with thumb or finger OA published in the Journal of Alternative and Complementary Medicine in 2000 compared the injection of a mixture of dextrose and lidocaine (a pain reliever) with lidocaine alone. Researchers found that patients who received the dextrose combo injections had less pain when moving their fingers compared with those who got only lidocaine.

A trial of 38 knee OA patients published in 2000 in Alternative Therapies in Health and Medicine also compared dextrose plus lidocaine with lidocaine alone. This study showed that the people who got dextrose had substantially better outcomes than their lidocaine-only counterparts in terms of pain, swelling, knee buckling and knee flexibility.

Prolotherapy is somewhat better studied in other conditions, including chronic back pain, says rheumatologist Amanda Nelson, MD, assistant professor of medicine in the Division of Rheumatology, Allergy, and Immunology at the University of North Carolina (UNC) at Chapel Hill. A 2007 Cochrane Database review of five trials of prolotherapy for low-back pain, for example, found no evidence that prolotherapy alone improved pain, but did create benefits when combined with other therapies.

Questions Remain

It is important to emphasize that the studies by Dr. Rabago and others are preliminary, and more research is needed to confirm the effectiveness and long-term safety of prolotherapy for knee OA. As of 2014, prolotherapy is offered most often offered in sports medicine and orthopaedic practices, many of which emphasize the potential benefits of “regenerative” injectables, which also includes platelet-rich plasma and growth factors. Doctors are increasingly using injectables for OA, from alternative options like prolotherapy to more traditional corticosteroid and hyaluronic acid shots.

Brad Fullerton, MD, a physical medicine and rehabilitation doctor in private practice in Austin, TX, who has used prolotherapy to treat knee OA and other conditions since 1999, says he was drawn to the therapy because it let him “fix things I could never fix before.”

Anecdotal reports from individual practitioners, however positive, aren’t a replacement for rigorous clinical trials, experts say.

“Like platelet-rich plasma, prolotherapy suffers from a lack of well-thought-out, methodologically sound, large randomized trials, particularly with long-term follow-up,” says Dr. Nelson.

She notes prolotherapy isn’t taught in rheumatology training programs or included in professional guidelines – including the American Academy of Orthopaedic Surgeons' treatment guidelines for knee OA – because of this lack of evidence. “It’s not widely accepted by the medical community, and you won’t often find rheumatologists offering prolotherapy,” she says.  

Debate About Safety

Could prolotherapy be more harmful than helpful? Richard Loeser, MD, professor of rheumatology and director of basic and translational research at UNC’s Thurston Arthritis Research Center, says, “I don’t understand what dextrose could do to the joint that would be favorable, and I can imagine lots of things that would be harmful, especially over the long term.”  

Injecting dextrose into the joint might cause a buildup of damaging sugar molecules in joint tissues similar to those that form in people with diabetes, he says. “It’s also not known what sugar could do to the composition of synovial fluid [the fluid that lines and lubricates joints], and changing its composition could be harmful to cells it comes into contact with.”  

However, Dr. Fullerton’s experience treating hundreds of individuals with positive, safe results makes him passionate about the therapy. He notes that he treats a number of doctors whom he suspects don’t share their treatment choice with their patients.

“It doesn’t fit into the normal mix of things we’re taught, but with more research coming out, I think it will eventually see much wider use,” he says.   

Who Should Try It?

Dr. Rabago says he presents prolotherapy as an option in his family medicine practice, usually for patients who have tried two or more therapies, such as supervised physical therapy and weight loss, and who still have pain and other symptoms that limit their activities. “As with all medical procedures, a clinical visit including a detailed history, exam and eligibility screening criteria, helps identify patients most likely to benefit from prolotherapy,” he says.

Likewise, in his Austin clinic, Dr. Fullerton typically offers prolotherapy (usually in combination with physical therapy) to people who’ve tried other treatments and haven’t gotten relief. “Most patients notice improvement after two treatments,” he says. “If they don’t feel improvement by then, it’s time to reassess the patient and adjust treatment.”

But until there’s better evidence it works and is safe in the long term, prolotherapy isn’t something Dr. Nelson would suggest to many of her patients.

“If people are interested in complementary and alternative therapies like acupuncture, it might be an option they’d like to explore,” she says, noting results of prolotherapy depend heavily on how injections are placed and what solution is used. “Everyone does it a little differently, and the Wisconsin group’s results, for example, are specific to them,” she says.   

Prolotherapy can be expensive. Insurance rarely covers the procedure, and per-session costs range from about $250 to $400.

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