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.

bigstock-Woman-suffering-from-pain-in-k-18060380.jpg

"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.

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   image courtesy of Nate Edwards/BYU

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.