‘Great Potential’ in Stem Cell Therapies for Knee Osteoarthritis

By Pat Anson, PNN Editor

Osteoarthritis of the knee is one of the most common forms of arthritis, causing progressive damage and thinning of cartilage in the knee joint.  Over 32 million American adults have knee osteoarthritis (OA), but most are treated with injections or pain medications that provide only temporary relief and often have side effects.

Could stems cells provide a more effective and long-lasting treatment for knee OA? Clinical trials have had mixed results so far, so a group of researchers in China conducted a meta-analysis of nearly 1,200 studies, weeding out the ones that were poorly designed or biased.

They eventually settled on 16 studies involving 875 patients with knee OA, most of them high quality studies that were randomized with control groups to compare results with.

Their findings, published in the Journal of Orthopaedic Research, show that stem cell treatment was associated with significant reductions in patient-reported pain from the third month onwards.

The most pain relief came from mesenchymal stem cells (MSCs) derived from a patient’s own body fat (adipose tissue) and stem cells derived from umbilical cord blood. Injections of MSCs derived from a patient’s fat provided better pain relief than stem cells from other donors and led to the most recovery of knee joint function.

“Stem cell transplantation proved safe and effective for knee osteoarthritis treatment,” the authors wrote. “Different sources of stem cells have a good effect on alleviating knee joint pain, restoring knee joint function, and minimizing patient trauma.”

The researchers said there was “great potential” for MSC therapy in the treatment of knee OA, but larger studies were needed to confirm their findings.

“The safety and efficacy of MSC therapy require rigorous validation with a larger sample size before clinical application. From the perspectives of relieving knee joint pain, promoting knee joint function recovery, and reducing patient trauma, umbilical cord‐derived stem cells should be considered as a priority option, followed by ADSCs (adipose stem cells), and finally bone marrow‐derived stem cells.”

In 2019, a small Canadian study found that stem cells collected from a patient’s bone marrow significantly reduced knee pain from osteoarthritis for as long as a year. But that study only involved 12 patients.

FDA Foot Dragging

Why are there so few good quality studies? Stem cell promoters have long complained about foot dragging by the Food and Drug Administration, which has been reluctant to approve new stem cell therapies that are not tested in randomized, double-blind, placebo-controlled studies — the so-called “gold standard” in clinical trials.

The FDA sent warning letters to 20 stem cell manufacturers and clinics in 2019, saying they were in violation of FDA guidance requiring stem cells to undergo “minimal manipulation.” The agency said the science behind stem cells made from a patient’s own tissue had not been proven safe and effective.

“There’s a false premise being asserted by some in the field that a product derived from a person’s own body and then manipulated and reinserted for another use different from the one it played in its original location is not subject to FDA regulation,” then FDA commissioner Scott Gottlieb, MD, and FDA Biologics Center Director Peter Marks, MD, said in a joint statement.

Critics say the FDA is still slowing down stem cell research, despite a pledge to approve 10 to 20 cell or gene therapies annually by 2025. So far this year, the agency has only approved five.  

“Despite signs of progress and a strong commitment from FDA leadership to improve its readiness for these cutting-edge therapies, the agency remains far off pace. Its risk-averse approach and culture that’s slow to adapt to new science could become a curse for many patients and the scientific field as a whole, with investment in biotech chilling in recent quarters,” Richard Burr, a policy adviser for health and life sciences consultant DLA Piper, wrote in an op/ed published in STAT News.

Burr is a former U.S. senator and congressman from North Carolina.

“During my time in Congress, I was one of the FDA’s toughest critics, but I also fiercely defended its mission because I believe in it. The FDA now has an opportunity to transform its oversight of cell and gene therapies and deliver on promises made to patients,” Burr said.

Steroid Injections May Worsen Knee Arthritis

By Pat Anson, PNN Editor

Two new studies are raising doubts about a commonly used treatment for knee osteoarthritis, a progressive and painful condition found in many older adults. Corticosteroid injections in the knee are often used to relieve osteoarthritis pain by reducing inflammation in the joint, with the relief lasting for days, weeks or sometimes months.

But a new long-term study by researchers at the University of California, San Francisco (UCSF) found that corticosteroid injections appear to worsen the progression of knee osteoarthritis compared to patients who received injections of hyaluronic acid, a polymer gel that acts as a lubricant and shock absorber.

UCSF researchers followed 210 patients with knee osteoarthritis (OA). Seventy of the patients received injections of either corticosteroids or hyaluronic acid, while the rest received no injections and served as a control group. MRI scans were performed on all participants at the start of the study and again two years later, focusing on the meniscus, bone marrow lesions, cartilage, joint effusion and ligaments.

“This is the first direct comparison of corticosteroid and hyaluronic acid injections using the semi-quantitative, whole organ assessment of the knee with MRI,” said Upasana Upadhyay Bharadwaj, MD, a research fellow in the Department of Radiology at UCSF.

In findings presented this week at the annual meeting of the Radiological Society of North America (RSNA), Bharadwaj reported that corticosteroid injections were significantly associated with the progression of knee OA, specifically in the lateral meniscus, lateral cartilage and medial cartilage.

Hyaluronic injections were not associated with the progression of knee OA. Patients who received hyaluronic acid showed a decreased progression of osteoarthritis, specifically in bone marrow lesions, compared to the control group. 

The findings are important because osteoarthritis is the most common form of arthritis, causing progressive joint damage and thinning of cartilage.  Over 32 million U.S. adults have knee OA, and about 10% of them receive corticosteroid or hyaluronic injections.

“While both corticosteroid and hyaluronic acid injections are reported to help with symptomatic pain relief for knee osteoarthritis, our results conclusively show that corticosteroids are associated with significant progression of knee osteoarthritis up to two years post-injection and must be administered with caution,” Bharadwaj said. “Hyaluronic acid, on the other hand, may slow down progression of knee osteoarthritis and alleviate long term effects while offering symptomatic relief.

“Knowing the long-term effects of these injections will help osteoarthritis patients and clinicians make more informed decisions for managing the disease and the pain it causes.”

In a second study presented at the RSNA’s annual meeting, researchers at the Chicago Medical School compared X-ray images of 50 patients with knee OA who received injections of corticosteroids to 50 patients who received injections of hyaluronic acid. Another 50 patients who had no injections served as a control group. Like the UCSF study, X-rays of all patients were taken at the start of the study and again two years later.

The findings mirrored those found in the first study. Patients injected with corticosteroids had significantly more osteoarthritis progression, including medial joint space narrowing, a hallmark of the disease.

“Even though imaging findings for all patients were similar at baseline, the imaging hallmarks of osteoarthritis were worse two years later in patients who received corticosteroid injections compared to patients who received hyaluronic acid injections or no treatment at all,” said Azad Darbandi, a researcher and medical student.

“The results suggest that hyaluronic acid injections should be further explored for the management of knee osteoarthritis symptoms, and that steroid injections should be utilized with more caution.”

The Mayo Clinic recommends that corticosteroid injections be limited to once every six weeks, and that knee OA patients receive injections no more than three or four times a year.

There was a third long-term study presented at the RSNA meeting that debunked another common treatment for knee OA: non-steroidal anti-inflammatory drugs (NSAIDs). UCFS researchers found that NSAIDs worsen inflammation and weaken cartilage in patients with osteoarthritis, contributing to a painful joint condition called synovitis. MRI imaging at the start of the study found joint inflammation and cartilage quality were worse in patients taking NSAIDs, and their knee joints deteriorated even more after four years. 

NSAIDs May Worsen Arthritis Inflammation

By Pat Anson, PNN Editor

Ibuprofen, naproxen and other non-steroidal anti-inflammatory drugs (NSAIDs) are often recommended as safer and more effective pain relievers than opioids. As evidence, anti-opioid activists often cite a 2018 study that found NSAIDs worked “significantly better” than opioids in reducing pain intensity for patients with osteoarthritis.

That study by VA researcher Erin Krebs, MD, is cited nearly a dozen times in the newly revised CDC opioid guideline, which recommends that patients avoid opioids and use topical or oral NSAIDs for osteoarthritis pain.

But according to a new long-term study, NSAIDs may actually worsen inflammation and weaken cartilage in patients with knee osteoarthritis, contributing to a painful joint condition called synovitis.

“The goal of our study was to analyze whether NSAID treatment influences the development or progression of synovitis and to investigate whether cartilage imaging biomarkers, which reflect changes in osteoarthritis, are impacted by NSAID treatment,” says lead author, Johanna Luitjens, MD, a postdoctoral scholar in the Department of Radiology and Biomedical Imaging at the University of California, San Francisco.

“NSAIDs are frequently used to treat pain, but it is still an open discussion of how NSAID use influences outcomes for osteoarthritis patients. In particular, the impact of NSAIDs on synovitis, or the inflammation of the membrane lining the joint, has never been analyzed using MRI-based structural biomarkers.”

Luitjens and her colleagues enrolled 277 people with moderate to severe osteoarthritis who used NSAIDs for at least one year, comparing them to a control group of 793 patients who were not treated with NSAIDs. All participants underwent an MRI of the knee at the start of the study and had another MRI four years later. 

The results showed no long-term benefits from NSAID use. The initial MRIs found joint inflammation and cartilage quality were worse in the participants taking NSAIDs, and their knee joints deteriorated even more after four years. 

“In this large group of participants, we were able to show that there were no protective mechanisms from NSAIDs in reducing inflammation or slowing down progression of osteoarthritis of the knee joint,” said Luitjens, who will present her findings next week at the annual meeting of the Radiological Society of North America (RSNA).

Luitjens says there are two possible reasons for the ineffectiveness of NSAIDs. One is that the anti-inflammatory effects of NSAIDs may not be sufficient to prevent synovitis. It’s also possible that patients with synovitis who use NSAIDs may be more physically active due to pain relief, which could have worsened their synovitis. 

In either case, Luitjens believes more evidence is needed to support the continued use of NSAIDs as a treatment for osteoarthritis.

“The use of NSAIDs for their anti-inflammatory function has been frequently propagated in patients with osteoarthritis in recent years and should be revisited, since a positive impact on joint inflammation could not be demonstrated,” she said.

The 2018 Krebs study did not look at how NSAIDs affected joint inflammation. It focused mainly on pain intensity, function and quality of life, and found few differences between opioids and NSAIDs, leading Krebs to conclude that opioids were “not superior” to NSAIDs. As my late colleague Roger Chriss pointed out, researchers also found no harmful effects in patients who took opioids for a year. There was no opioid misuse, addiction or overdoses — a detail rarely mentioned in news coverage of the study.

Osteoarthritis is a joint disorder that leads to thinning of cartilage and progressive joint damage. Knee osteoarthritis is quite common and affects over 250 million people worldwide. Nearly 40 percent of Americans over the age of 45 have some degree of knee osteoarthritis.

Experimental Gel Could Replace Damaged Knee Cartilage

By Pat Anson, PNN Editor

Clinical trials on humans may begin as soon as next year on an experimental hydrogel designed to replace damaged cartilage in arthritic knees, according to researchers at Duke University, who say the gel is up to three times stronger than natural cartilage.   

Implants made of the material are currently being tested on sheep by Sparta Biomedical, a medical device company that is developing a line of synthetic cartilage.

“If everything goes according to plan, the clinical trial should start as soon as April 2023,”  Benjamin Wiley, PhD, Sparta’s chief technology officer and a Duke chemistry professor, said in a press release. “I think this will be a dramatic change in treatment for people.”

Wiley says hydrogel implants could someday be used as an alternative to total knee replacement surgery, one of the fastest growing elective procedures in the United States. About one in six adults suffer from knee osteoarthritis, a painful disorder that leads to thinning of cartilage and progressive joint damage.

Often considered the treatment of last resort, knee replacement surgery can be problematic. Studies have found that about a third of the patients who have their knees replaced continue to experience chronic pain. The artificial joints also have a limited life span and sometimes need to be replaced after a few years.   

“There's just not very good options out there,” said Wiley.

To make the hydrogel, Wiley and his team took thin sheets of cellulose fibers and infused them with a water absorbing polymer, creating a Jello-like material that is surprisingly strong. The cellulose fibers act like the collagen in natural cartilage, giving the gel strength when pulled or stretched.

Natural cartilage can withstand up to 8,500 pounds per inch of tugging and squishing before reaching a breaking point. The hydrogel can handle even more pressure and is 66% stronger than cartilage when compressed, the equivalent of parking a car on a postage stamp.

“It’s really off the charts in terms of hydrogel strength,” Wiley says.

Duke researchers first reported in 2020 that they had developed a hydrogel strong enough for knees, but using it to replace cartilage presented some design challenges. Hydrogels are difficult to attach directly to bone or cartilage to keep them from breaking loose or sliding off during intense activities.

They got around that problem by cementing and clamping the hydrogel to a titanium base, which is then anchored into a small hole where the damaged cartilage used to be. Tests showed the design stays fastened 68% more firmly than natural cartilage on bone.

In wear tests, the researchers took the hydrogel and natural cartilage and spun them against each other a million times, with a pressure similar to what the knee experiences during walking. Using high-resolution X-ray imaging, they found that the artificial cartilage held up three times better than the real thing.

DUKE UNIVERSITY IMAGE

And because the hydrogel mimics the smooth and cushiony nature of real cartilage, it protects other joint surfaces from being damaged as they slide against the implant. Other researchers have tried replacing cartilage with implants made of metal or polyethylene, but because those materials are stiffer than cartilage, they can chafe against other parts of the knee.

The research study, published in the journal Advanced Functional Materials, was funded by Sparta Biomedical and Duke University.

An experimental gel also shows promise as a treatment for low back pain caused by degenerative disc disease, according to a recent small study. Hydrafil – an injectable gel developed by ReGelTec – fills in cracks and tears in damaged discs, restoring the disc’s structural integrity. The injection procedure is minimally invasive and only takes about 30 minutes.

Walking Reduces Pain From Knee Osteoarthritis

By Pat Anson, PNN Editor

It may seem counterintuitive, but a new study suggests that walking may be the best medicine to reduce knee pain from osteoarthritis.

Nearly 40 percent of Americans over the age of 45 have some degree of knee osteoarthritis, a progressive joint disorder caused by inflammation of soft tissue, which leads to thinning of cartilage and joint damage. Osteoarthritis (OA) of the knee is not to be taken lightly, as studies have found that it is strongly associated with early death, high blood pressure, diabetes, elevated cholesterol and cardiovascular disease, particularly for women.

Moderate exercise like walking may help prevent all of those health problems.

In a multi-year study of 1,212 people over the age of 50, researchers at Baylor College of Medicine found that participants who walked for exercise at least 10 times had 40% less risk of developing frequent knee pain than non-walkers.

“Until this finding, there has been a lack of credible treatments that provide benefit for both limiting damage and pain in osteoarthritis,” said Grace Hsiao-Wei Lo, MD, assistant professor of Immunology, Allergy and Rheumatology at Baylor and lead author of the study published in Arthritis & Rheumatology.

“These findings are particularly useful for people who have radiographic evidence of osteoarthritis but don’t have pain every day in their knees,” Lo explained in a press release. “This study supports the possibility that walking for exercise can help to prevent the onset of daily knee pain.  It might also slow down the worsening of damage inside the joint from osteoarthritis.”  

Lo says walking for exercise has other health benefits, such as improved cardiovascular health and decreased risk of obesity, diabetes and even some cancers. Walking is also a free activity with minimal side effects.

“People diagnosed with knee osteoarthritis should walk for exercise, particularly if they do not have daily knee pain,” says Lo, who is chief of rheumatology at the Michael E. DeBakey VA Medical Center in Houston. "If you already have daily knee pain, there still might be a benefit, especially if you have the kind of arthritis where your knees are bow-legged.”

Positive Results From Stem Cell Trial for Knee Osteoarthritis

By Pat Anson, PNN Editor

A California stem cell company has announced positive results from a small, early-stage clinical trial of an experimental stem cell therapy for knee osteoarthritis.  

The Phase 1/2a trial conducted by Personalized Stem Cells (PSC) involved 39 patients with knee osteoarthritis who were given a single injection of autologous mesenchymal stem cells derived from their own body fat. Safety was the primary objective of the trial and there were no serious adverse events reported by the company.

The secondary objective of the trial was to assess the effectiveness of the therapy with the Knee Injury and Osteoarthritis Outcome Score (KOOS), a survey that asks patients about their pain, other symptoms, daily function, quality of life, and recreational activities. Nearly 80% of study participants improved above the “minimal important change” (MIC), with an average improvement over baseline of 2.2 times the MIC.

Osteoarthritis is a progressive joint disorder caused by painful inflammation of soft tissue, which leads to thinning of cartilage and joint damage in the knees, hips, fingers and spine.

Results from the PSC study have been submitted to the FDA for review. The company hopes to get approval for a larger, Phase 2 randomized study of its stem cell therapy later this year.  

“We are pleased at the strong safety profile and efficacy results in this FDA-approved clinical study of stem cell therapy for knee osteoarthritis,” said PSC founder and CEO, Dr. Bob Harman. “We are proud to have reached this milestone in our first FDA approved clinical trial. This data supports our progress in the larger placebo-controlled clinical study.”

Veterinarians Already Using Stem Cells

While the FDA has approved hundreds of clinical trials of stem cells, it has not approved a single stem cell product as a treatment for arthritis or any orthopedic condition. That hasn’t stopped stem cell clinics from offering regenerative medicine to patients or veterinarians from using it on animals.

VetStem Biopharma, the parent company of PSC, pioneered the use of adipose derived stem cells in veterinary medicine. Its laboratory has processed stem cells for nearly 14,000 dogs, cats, horses and other animals for use by veterinarians in the U.S. and Canada.

“The 15 years of veterinary experience with adipose derived stem cell therapy of our parent company, VetStem Biopharma, provided the basis for our FDA study submission and approval and provided valuable insights into the study design and conduct,” said Harman.

In addition to the Phase 2 trial for osteoarthritis, PSC plans to pursue FDA approval for a stem cell trial to treat traumatic brain injuries in humans. A clinical study using PSC’s stem cell platform to treat respiratory distress syndrome in COVID-19 patients is currently underway.

Injections of Tiny Particles Reduce Osteoarthritis Knee Pain

By Pat Anson, PNN Editor

A minimally invasive procedure significantly reduces pain and inflammation caused by knee osteoarthritis, according to preliminary research being presented this week at the annual meeting of the Society of Interventional Radiology.

Geniculate artery embolization (GAE) is a relatively new procedure in which thousands of microscopic particles are injected into arthritic knees. The particles reduce inflammation by disrupting the abnormal flow of blood caused by osteoarthritis (OA), a joint disorder that causes thinning of cartilage and progressive joint damage. As the cartilage breaks down, it releases enzymes that cause inflammation and pain.

GAE takes about one to two hours, and many patients with knee OA report significant improvement in pain and physical function that can last up to a year.

"Prior to treatment, patients' knee pain had taken over their whole life," said lead researcher Siddharth Padia, MD, a professor of radiology at UCLA Health. "But after treatment, patients who initially could walk only three or four blocks were walking three miles. Some were able to do away with walking aids, such as canes, while others reported being in a better mood now that they were living without pain."

For their Phase 2 study, Padia and his colleagues enrolled 40 patients with knee OA who were not candidates for total knee replacement, and who failed to benefit from pain relievers, joint injections and physical therapy.

Catheters were inserted into arteries leading to the knees through pinhole incisions in the patients’ hips. The microscopic particles — called Embozene microspheres — were then slowly injected through the catheter into the knees. Each patient was evaluated for pain and adverse events at one week; one, three and six months; and one year after the treatment.

Researchers say patients saw benefits as soon as three days after the procedure. Average pain levels decreased from 8 out of 10 before GAE to 3 out of 10 within the first week. Most patients reported more than 50% reduction in their pain levels at the one-year follow up.

Adverse events, such as skin ulceration and small bone infarction – the death of bone tissue due to reduced blood supply -- were reported by 9 patients, but resolved without treatment.

Embozene microspheres are made by Boston Scientific and are currently used in the treatment of vascular tumors, uterine fibroids and arterial malformations. They must be carefully injected into affected tissue to prevent them from circulating in the blood and reaching healthy tissue and organs.

“This prospective trial demonstrates that GAE is highly effective and durable in reducing symptoms due to moderate to severe knee OA that is refractory to other conservative therapy, and has an acceptably low toxicity profile,” researchers concluded.

The UCLA researchers plan to conduct a larger, randomized trial to determine which patients may benefit most from GAE and the impact it has on slowing the progression of arthritis.

Results from other studies on the use of GAE are also being presented at the meeting of the Society of Interventional Radiology. One review found that GAE can be effective for patients who don't respond well to conservative treatments for knee OA, but cautioned that “definitive conclusions can't be made on the true efficacy of GAE until studies are done with longer follow up and larger patient numbers.”

Turmeric Moderately Effective in Treating Osteoarthritis Pain

By Pat Anson, PNN Editor

A yellow spice used in food and traditional Chinese medicine – turmeric – is effective in treating osteoarthritis knee pain, according to small placebo-controlled study published in the Annals of Internal Medicine.

Researchers from the University of Tasmania, Australia randomly assigned 70 participants with knee osteoarthritis to receive either 2 capsules per day of turmeric or a placebo. Changes in pain and swelling in the knees were assessed by questionnaire and MRIs.

After 12 weeks, researchers found that patients taking daily turmeric supplements reported moderate improvement in pain compared to the placebo group. They also consumed fewer pain medications. There was no difference in the cartilage or structural changes in the knees between the two groups.

Due to the modest effect of turmeric on knee pain, small sample size and short duration of the study, researchers suggest that multi-center clinical trials with more patients are needed to assess the clinical significance of their findings.

Osteoarthritis (OA) is a joint disorder that leads to thinning of cartilage and progressive joint damage. Knee OA is quite common and affects over 250 million people worldwide. Women are more likely than men to have knee OA and to have more severe pain. Studies have also found that women with knee OA are at greater risk of early death from cardiovascular disease.

No disease-modifying drugs are currently available to treat osteoarthritis. Common pain relievers, such as acetaminophen (paracetamol) and non-steroidal anti-inflammatory drugs (NSAIDs) have only mild to moderate effects on OA pain and can have side events.

Turmeric is a medicinal herb that is used in Indian, Southeast Asian and Middle Eastern foods as a spice. Curcumin is the main active ingredient in turmeric. It has potent anti-inflammatory effects and is a strong antioxidant.

In a PNN guest column, Judie Plumley reported that curcumin supplements helped ease the chronic back pain that left her bedridden. “I am amazed with the results!  My pain is now bearable. I can do about twice as much as I could before, and I am spending much less time in bed,” wrote Plumley.

Turmeric and curcumin are often touted as treatments for everything from diabetes and depression to cancer and high cholesterol. However, research results on their effectiveness have been mixed.

Experimental Drug Rebuilds Cartilage in Knee Osteoarthritis Patients

By Pat Anson, PNN Editor

An experimental treatment shows promise in slowing the progression of knee osteoarthritis by increasing the thickness of cartilage in the knee joint, according to results of an early clinical trial published in the Journal of the American Medical Association (JAMA).

Researchers at the University of Maryland School of Medicine gave 549 volunteers with knee osteoarthritis injections of the drug sprifermin or a placebo. Sprifermin is a disease modifying drug that stimulated the production of cartilage-producing cells in animal studies.

The researchers found that participants who received a 100 microgram dose of sprifermin either twice or once yearly experienced a statistically significant but slight gain in joint cartilage thickness after two years.  Those given smaller doses had smaller gains in cartilage that were not statistically or clinically significant.

"While the increase in cartilage thickness is a positive sign, we do not know at this point whether it has any clinical significance," said lead investigator Marc Hochberg, MD, a Professor of Medicine at UMSOM. "It is not known whether those who experience increased cartilage thickness over time will be able to avoid or delay knee replacement surgery."

Interestingly, patients treated with a high dose of sprifermin did not experience any significant improvement in their arthritis symptoms – such as pain and stiffness -- compared to those given lower doses or placebo injections.

All of the injections were stopped after 18 months. The Phase 2 study is designed to continue for a total of five years and future analyses of the findings are planned.

About 10 percent of Americans over age 60 have knee osteoarthritis, a progressive condition caused by the breakdown of joint cartilage. Knee osteoarthritis causes pain, physical disability, lower quality of life and is associated with early death and cardiovascular problems.

The pain is usually treated with over-the-counter pain relievers, anti-inflammatory drugs, steroid injections, and sometimes surgery. No disease-modifying osteoarthritis drugs have been approved in the United States or Europe.

Arthroscopic and knee replacement surgeries are increasingly being used to treat knee osteoarthritis. But a number of recent studies have found the arthroscopic surgery does not relieve knee pain any better than physical therapy or over-the-counter pain relievers. Researchers have also found that about a third of patients who had knee replacement surgery continued to have pain after the procedure.

Stem Cells Reduce Pain from Knee Osteoarthritis

By Pat Anson, PNN Editor

A small new study has demonstrated that stem cells collected from a patient’s own bone marrow can significantly reduce pain caused by osteoarthritis of the knee.

In the first clinical trial of its kind in Canada, researchers collected mesenchymal stromal cells (MSCs) from the spines of 12 middle-aged patients with moderate to severe knee osteoarthritis. These “autologous” cells – stem cells derived from a patient’s own fat or bone tissue – were then processed and injected back into the patients’ knees at different doses.

Researchers then followed the patients for the next 12 months, using MRI imaging, biomarkers, molecular fingerprinting and the patient's own assessment of how they felt.

"Our goal was to test for safety as well as to gain a better understanding of MSC dosing, mechanisms of action and donor selection," said lead author Sowmya Viswanathan, PhD, Arthritis Program at the Krembil Research Institute, University Health Network in Toronto.

At the end of the study period, researchers said there were significant improvements in all 12 patients’ pain levels, stiffness and quality of life. The study also showed that the MSCs were safe at all the doses tested and that the higher the dose, the more effective the outcome.

"We also obtained novel insights into a potential anti-inflammatory mechanism of action of these cells in osteoarthritic knee joints. We noted that donor heterogeneity is an important factor, and our assembled panel of genes helps us identify cells which are potent in osteoarthritis. These are important findings which we hope to translate into a larger, powered clinical trial as part of our next steps," said Viswanathan, who reported the findings in the journal Stem Cells Translational Medicine.

Over 250 million people worldwide suffer from knee osteoarthritis (OA), which causes thinning of cartilage and progressive joint damage. Nearly 40 percent of Americans over the age of 45 have some degree of knee OA.

Knee replacement and arthroscopic knee surgeries are commonly used to treat knee OA, even though many studies show they have limited effectiveness. A 2017 study in The British Medical Journal  of over 7,400 patients who had knee replacement surgery found the procedure often had minimal effects on quality of life and wasn’t worth the cost.

Arthroscopic surgery is less invasive than a total knee replacement, but studies also show it is often not effective. In 2017, an international panel of experts reviewed 25 studies involving nearly two million patients and concluded that arthroscopic surgery does not improve long term pain or function in patients with knee conditions such as osteoarthritis.

Because these conventional treatments often fail, there is growing interest in the use of stem cells to treat knee problems. The FDA, however, takes a dim view of autologous stem cells and released guidance in 2017 that requires the cells to undergo “minimal manipulation.”

The FDA recently sent letters to 20 stem cell manufacturers and clinics warning them they were violating FDA regulations. The agency says the science behind autologous cells is still in its early stages and they have not been proven to be safe and effective.

“There’s a false premise being asserted by some in the field that a product derived from a person’s own body and then manipulated and reinserted for another use different from the one it played in its original location is not subject to FDA regulation just because it originated from the person it was given back to,” then FDA commissioner Scott Gottlieb, MD, and Biologics Center Director Peter Marks, MD, said in a statement.

“We’ve seen too many cases of sponsors claiming that cells aren’t subject to FDA regulation just because the cells originated from the same patient to whom the eventual manufactured product is being given. And we’ve seen too many cases of companies making unsubstantiated claims that these treatments prevent, treat, cure or mitigate disease where the products have sometimes led to serious patient harm.”

Can Running Help Prevent Osteoarthritis?

By Pat Anson, Editor

People suffering from aching muscles and joint pain are often told that exercise is the best remedy. It sounds counter-intuitive, but now there’s evidence that running can actually reduce joint inflammation – at least in the knees.

"It flies in the face of intuition," says Matt Seeley, an associate professor of exercise science at Brigham Young University. "This idea that long-distance running is bad for your knees might be a myth."

Seeley and his colleagues conducted a small study of six healthy men and women who ran on treadmills for 30 minutes. Blood samples and synovial fluid from their knee joints were collected both before and after they ran.

The researchers found that two inflammatory markers in the synovial fluid -- cytokines named GM-CSF and IL-15 -- decreased in concentration in the runners after a treadmill session.  Cytokines are small proteins released by cells that play an important role in pain and inflammation.

"What we now know is that for young, healthy individuals, exercise creates an anti-inflammatory environment that may be beneficial in terms of long-term joint health," said Robert Hyldahl, a BYU assistant professor of exercise science.

image courtesy of Nate Edwards/BYU

The findings, published in the European Journal of Applied Physiology, indicate that running may be chondroprotective, which means exercise may help delay the onset of joint diseases such as osteoarthritis (OA), a disorder that leads to thinning of cartilage and progressive joint damage. Nearly 40 percent of Americans over the age of 45 have some degree of knee OA.

“This is the first study to evaluate a wide panel of inflammatory mediators in the knee joints of healthy subjects following running. Our results suggest that running decreases intra-articular inflammation and brings to light a novel potential mechanism for the chondroprotective nature of exercise in non-pathologic knees,” the BYU researchers said.

The researchers now plan to study subjects with previous knee injuries, by conducting similar tests on people who have suffered ACL injuries.

"This study does not indicate that distance runners are any more likely to get osteoarthritis than any other person," Seeley said. "Instead, this study suggests exercise can be a type of medicine."

Vitamin D Ineffective for Knee Osteoarthritis

By Pat Anson, Editor

Recent studies have suggested that Vitamin D supplements may help reduce pain from fibromyalgia, arthritis and other chronic conditions.

But the “sunshine vitamin” did not relieve pain or stop cartilage loss in patients with knee osteoarthritis, according to new research published in JAMA.

Osteoarthritis is a joint disorder that leads to thinning of cartilage and progressive joint damage. Knee osteoarthritis (OA) is very common and affects over 250 million people worldwide. Nearly 40 percent of Americans over the age of 45 have some degree of knee OA.

Over 400 people with knee OA and low serum levels of Vitamin D participated in the placebo controlled study in Australia and Tasmania. They were divided into two groups; with one receiving Vitamin D supplements and the other a placebo.

Over the course of the two-year study, knee pain, stiffness and physical function were measured with the WOMAC pain scale and MRI scans were used to monitor cartilage volume, defects and bone marrow lesions.  

While the supplements did increase Vitamin D blood levels, they did not reduce knee pain. MRI’s also showed no significant differences in cartilage between the two groups.

“Vitamin D supplementation, when compared with placebo, did not result in significant differences in change in MRI-measured tibial cartilage volume or change in WOMAC knee pain score over 2 years. These findings do not support the use of vitamin D supplementation for preventing tibial cartilage loss or improving WOMAC knee pain among patients with knee osteoarthritis,” said lead author Changhai Ding, MD, of the University of Tasmania.

Vitamin D helps control levels of calcium and phosphate in the body and is essential for the formation of strong bones and teeth. Vitamin D also modulates cell growth, improves neuromuscular and immune function, and reduces inflammation

Vitamin D deficiency – a condition known as hypovitaminosis D -- is caused by poor nutritional intake of Vitamin D, inadequate sunlight or conditions that limit Vitamin D absorption. The most severe type of hypovitaminosis D causes general body pain, especially in the shoulder, rib cage, lumbar and pelvic regions.

Researchers at National Taiwan University Hospital recently found a “positive crude association” between fibromyalgia and hypovitaminosis D.  According to the Vitamin D Council, low levels of Vitamin D could be the result of fibromyalgia, rather than the cause of the disease.

Sources of Vitamin D include oily fish and eggs, but it can be difficult to get enough through diet alone. Ultraviolet rays in sunlight are the principal source of Vitamin D for most people.

Arthroscopic Knee Surgery Not Cost-Effective

By Pat Anson, Editor

Another study is raising doubts about the value of arthroscopic knee surgery, a procedure that is routinely used to treat osteoarthritis and other chronic knee problems. Researchers at Western University in Canada say the surgery provides no additional benefit compared to physical therapy, exercise and medication.

Over 250 million people worldwide suffer from knee osteoarthritis (OA), which causes thinning of cartilage and progressive joint damage. Nearly 40 percent of Americans over the age of 45 have some degree of knee OA.

Investigators at Western’s Bone and Joint Institute analyzed the cost-effectiveness of arthroscopic  surgery, a type of “keyhole” surgery in which the surgeon makes a small incision in the knee and inserts a tiny camera and instruments to diagnose and repair damaged ligaments or torn meniscus.

Over 850,000 arthroscopies are performed every year to relieve knee pain in the UK and the United States alone.

"We previously showed in a randomized clinical trial that arthroscopy for knee osteoarthritis provided no benefit over optimized non-operative care. Despite that finding, and subsequent similar studies, the surgery is still commonly performed," says Trevor Birmingham, the Canada Research Chair in Musculoskeletal Rehabilitation at Western's Faculty of Health Sciences. "That's why we felt it was important to do the accompanying cost-effectiveness analysis."

The two-year study, published in the journal BMJ Open, found that arthroscopic knee surgery is “not an economically attractive treatment option” compared to non-operative treatments such as physical therapy, exercise and medication. Depending on insurance, hospital charges and the surgeon, arthroscopic surgeries cost about $4,000.

“Patients who received non-operative therapies showed similar improvements in pain, function, and quality of life compared to those who also received surgery, at a significantly lower cost,” says lead author Jacquelyn Marsh, a Post-Doctoral Fellow in Health Economics at Western University.

While most people do feel better after knee arthroscopy, randomized clinical trials found that patients improve to a similar extent when they receive non-operative treatments or ‘sham’ surgery, where the patient receives anesthesia but doesn’t actually receive the surgical treatment.

“When that body of evidence is coupled with the present economic analysis, one has to question whether health care funds would be better spent elsewhere,” said Birmingham.

A 2014 report by a German health organization also found arthroscopic  surgery does not relieve pain any better than physical therapy or over-the-counter pain medications.

Another study published last year in the The BMJ called the benefit of knee surgery “inconsequential.” Researchers in Denmark and Sweden reviewed 9 studies on arthroscopic knee surgeries and found that the surgery provided pain relief for up to six months, but without any significant benefit in physical function. Risks from the surgery are rare, but include deep vein thrombosis, infection, pulmonary embolism, and death.

"It is difficult to support or justify a procedure with the potential for serious harm, even if it is rare, when that procedure offers patients no more benefit than placebo," wrote Professor Andy Carr from Oxford University’s Institute of Musculoskeletal Sciences in an accompanying editorial.

Carr said thousands of lives could be saved if the surgery was discontinued or performed less often.

Supplements Help Relieve Pain of Osteoarthritis

By Pat Anson, Editor

Two natural dietary supplements are effective at relieving pain and stiffness caused by osteoarthritis, without the side effects caused by non-steroidal anti-inflammatory drugs (NSAIDs), according to two new research studies.

One study found that a combination of glucosamine and chondroitin was effective in treating knee osteoarthritis (OA), while the other study examined an herbal treatment used for thousands of years in Chinese medicine to treat joint pain.

Osteoarthritis is a progressive joint disorder caused by painful inflammation of soft tissue, which leads to thinning of cartilage and joint damage in the knees, hips, fingers and spine.

The first study was a meta-analysis (a study of studies) involving over 16,000 patients with knee OA. Published in the journal Scientific Reports, it is the first study of its kind to compare glucosamine, chondroitin, and the two in combination, against the NSAID celecoxib or a placebo in the treatment of knee OA.

Researchers found that the combination of glucosamine and chondroitin was associated with significant improvement in pain relief and functional enhancement, compared to placebo, without the high rate of gastrointestinal side effects in patients who received celecoxib.

There was "no significant difference" in pain relief between celecoxib and the glucosamine/chondroitin combination.

"This comprehensive analysis provides us with a wealth of historical data supporting the safety and efficacy of glucosamine and chondroitin in the management of joint health. It is consistent with recent findings suggesting that the efficacy of this combination is comparable to celecoxib in terms of relieving pain and improving function," said lead author Chao Zeng, MD, of the Department of Orthopaedics at Xiangya Hospital at Central South University in Changsha, China.

"This is important news for patients requiring long-term treatment, as the potential side-effect associated with profiles of NSAIDs such as celecoxib warrant consideration of alternative treatment options that are safe and effective."

Glucosamine and chondroitin are both found in healthy cartilage, which acts as a cushion between the bones in a joint. In dietary supplements, glucosamine can be harvested from shells and shellfish or made synthetically. Chondroitin can also be made in a lab, or manufactured from cartilage found in cows, pigs, sharks and other animals.

Chondroitin and glucosamine are popular in supplements used to treat joint pain, but according to the Arthritis Foundation, “most studies assessing their effectiveness show modest to no improvement compared with placebo in either pain relief or joint damage.” The American Academy of Orthopaedic Surgeons also recommends against their use.

The second, smaller study examined the effectiveness of Arthrem, a dietary supplement made in New Zealand that contains an herbal extract from the plant Artemisia annua (Qinghaosu), which has been used in Chinese medicine for more than 2,000 years.

Forty-two people with osteoarthritis of the knee or hip were enrolled in the randomized, controlled study, which was published in the journal Clinical Rheumatology. Researchers say patients who took an Arthrem capsule twice a day for 12 weeks had a significant reduction in pain and stiffness and an increase in their physical function.

"The published results show that the natural product, Arthrem, has potential as an anti-inflammatory/analgesic in osteoarthritis," said Dr. Sheena Hunt, study co-author and principal scientist for Promisia Integrative, the company that makes Arthrem and conducted the study.

"Particularly positive results were observed in a subset of patients with mild to moderate osteoarthritis. In this subgroup, the average magnitude of pain after 12 weeks of taking Arthrem was less than half of the value at the start of the study. Arthrem at this dose was also well tolerated with no treatment-related side effects."

Arthrem recently became available in the United States. Those who qualify can sign up for a free, no obligation, two month trial online at www.Arthrem.com.

Compared to pharmaceuticals, the U.S. Food and Drug Administration loosely regulates the $35 billion dietary supplement industry and many manufacturers' claims about their products are unverified.  The agency recently announced plans to tighten enforcement of the industry by creating a dietary supplement office.

The World Health Organization estimates that about 10% of men and 18% of women over age 60 have osteoarthritis.

Yoga Reduces Chronic Pain of Arthritis

By Pat Anson, Editor

A few weeks of yoga can significantly improve the health and mental well-being of people suffering from the two most common forms of arthritis, according to a new study at Johns Hopkins University.

Researchers found that 8 weeks of yoga classes reduced pain and improved the energy, mood and physical activity of patients with rheumatoid arthritis or knee osteoarthritis. The study, published in the Journal of Rheumatology, is believed to be the largest randomized trial to examine the effect of yoga on the physical and psychological health of arthritis sufferers.

"There's a real surge of interest in yoga as a complementary therapy, with 1 in 10 people in the U.S. now practicing yoga to improve their health and fitness," said Susan Bartlett, PhD, an adjunct associate professor of medicine at Johns Hopkins and associate professor at McGill University.

"Yoga may be especially well suited to people with arthritis because it combines physical activity with potent stress management and relaxation techniques, and focuses on respecting limitations that can change from day to day."

Rheumatoid arthritis (RA) is a chronic autoimmune disease in which the body’s own defenses attack joint tissues, causing pain, inflammation and bone erosion. About 1.5 million Americans and 1% of adults worldwide suffer from RA.

Knee osteoarthritis (OA) is even more common and affects over 250 million people worldwide. Nearly 40 percent of Americans over the age of 45 have some degree of knee OA, which causes thinning of cartilage and progressive joint damage.

Johns Hopkins researchers recruited 75 sedentary adults with either knee osteoarthritis or RA. Participants were randomly assigned to either a wait list or eight weeks of twice-weekly yoga classes, plus a weekly practice session at home. Their physical and mental well-being were assessed before and after the yoga sessions by researchers who did not know which group the participants had been assigned to.

Those doing yoga reported a 20% improvement in pain, energy levels, mood and physical function, including their ability to complete physical tasks. Walking speed also improved to a lesser extent, though there was little difference between the groups in tests of balance and upper body strength. Improvements in those who completed yoga were still apparent nine months later.

"For people with other conditions, yoga has been shown to improve pain, pain-related disability and mood," said Clifton Bingham III, MD, associate professor of medicine at Johns Hopkins University School of Medicine and director of the Johns Hopkins Arthritis Center.

"But there were no well-controlled trial of yoga that could tell us if it was safe and effective for people with arthritis, and many health professionals have concerns about how yoga might affect vulnerable joints given the emphasis on changing positions and on being flexible. Our first step was to ensure that yoga was reasonable and safe option for people with arthritis.”

Participants were screened by their doctors prior to joining the study, and continued to take their regular arthritis medication. Instructors in the yoga classes also had additional training to modify poses to accommodate people with limited physical ability.

“Find a teacher who asks the right questions about limitations and works closely with you as an individual. Start with gentle yoga classes. Practice acceptance of where you are and what your body can do on any given day," Bingham said.