Blood Test Predicts Knee Osteoarthritis Years Before Symptoms Start

By Pat Anson, PNN Editor

An experimental blood test could give doctors and patients a leg up in diagnosing and treating knee osteoarthritis, years before joint damage occurs and becomes visible on X-rays.

"Currently, you've got to have an abnormal X-ray to show clear evidence of knee osteoarthritis, and by the time it shows up on X-ray, your disease has been progressing for some time," says senior author Virginia Byers Kraus, MD, a professor of Medicine, Pathology, and Orthopedic Surgery at Duke University School of Medicine.

Kraus and her colleagues have devised a test that looks for serum biomarkers in the blood that can predict – with a fair amount of accuracy – the development of knee osteoarthritis (OA) up to 8 years before joint damage occurs. Osteoarthritis is the most common form of arthritis, affecting about 10% of men and 18% of women over age 60.

In previous studies, the biomarker test demonstrated 74% accuracy in predicting knee OA progression and 85% accuracy in diagnosing knee OA. The current study further refined the test by narrowing down the number of biomarkers from a dozen to only six.

Using a UK patient database, researchers used the refined test to analyze the blood of 200 middle-aged women with no chronic knee pain; half of whom were later diagnosed with OA and the other half without the disease. The study findings, published in the journal Science Advances, show the test correctly predicted knee OA with 77% accuracy within 6 years.

"What our blood test demonstrates is that it's possible to detect this disease much earlier than our current diagnostics permit," Kraus said in a news release. "This is important because it provides more evidence that there are abnormalities in the joint that can be detected by blood biomarkers well before X-rays can detect OA.

"Early-stage osteoarthritis could provide a 'window of opportunity' in which to arrest the disease process and restore joint health."

There are currently no diagnostic blood tests for OA and there is no cure. Treatment is limited to pain relievers and anti-inflammatory drugs that slow progression of the disease.

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CBD Ineffective for Osteoarthritis Knee Pain

By Pat Anson, PNN Editor

Cannabidiol (CBD) is often touted as an effective pain reliever for arthritis. Studies on animals and anecdotal reports from humans suggest that CBD – the non-psychoactive compound in cannabis -- has anti-inflammatory and pain-relieving effects on joint pain.

But in one of the first randomized, placebo-controlled clinical trials of CBD, researchers at Medical University of Vienna found that CBD is not an effective pain medication for knee osteoarthritis, even at high doses.

The study included 86 men and women who suffered from severe pain due to knee osteoarthritis,  a progressive condition caused by the breakdown of joint cartilage.in the knee. About 10 percent of people over age 60 have knee osteoarthritis (OA).

Half the participants received daily doses of CBD in capsules for eight weeks, titrating up to 600mg per day, which is considered a high dose. The other participants were given placebo capsules with no active ingredient. Neither group knew what they were taking.

The study findings, published in The Lancet Regional Health -- Europe, show that CBD did not have a stronger analgesic effect than the placebo. Adverse events were more common in the CBD group, with over half the participants (56%) reporting diarrhea, abdominal pain, fatigue and other mild side effects.

“Our results do not support the yet clinically unproven hopes for CBD as potential supplement or even replacement of potent analgesics, including opioids,” wrote lead author Sibylle Pramhas, MD, Department of Special Anesthesia and Pain Medicine at MedUni Vienna.

"Our study is the first to provide solid information on the lack of analgesic potential of CBD in a common chronic pain condition, due to the comparatively high oral dosage and the long observation period.”

This isn’t the first time CBD came up short in a clinical study. In 2017, Zynebra Pharmaceuticals tested a CBD gel for knee OA with mixed results. The Phase 2 study did not meet its primary goal of reducing the average pain score, although there were some indications the gel improved function and reduced pain severity. The company has since abandoned plans to use the gel for arthritis pain.

A more recent study of a CBD patch for knee osteoarthritis was withdrawn due to “inadequate funding.” Several other clinical studies of CBD for OA pain are underway or recruiting participants, but no results have been posted.

Currently, osteoarthritis knee pain is treated with analgesics such as acetaminophen (paracetamol), diclofenac, ibuprofen or tramadol. For the time being, they may be the best alternatives for pain relief.   

"CBD is not an alternative for pain therapy for osteoarthritis of the knee, so the search for more effective options must continue," says Pramhas.

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.

Lipofilling Improved Pain and Function in Patients with Finger Osteoarthritis

By Pat Anson, PNN Editor

People who suffer from painful arthritic fingers have few treatment options to choose from. They can wrap their hand in a splint, take anti-inflammatory drugs or get steroid injections into their finger joints – all of which provide only temporary relief. More invasive surgical treatments include joint fusions or reconstruction, which can impair hand motion and take weeks to recover from.

German researchers have found that a less invasive treatment commonly used in plastic surgery – injecting fat tissue from one part of the body into another -- can provide lasting improvements in pain and function for patients with finger osteoarthritis. The technique – called lipofilling – resulted in “highly significant clear improvement" with no complications in a small pilot study of 15 patients.     

"We believe that for our patients the reduction of pain represents the most striking and important result, which also has the most pronounced and highly significant effect," said co-author Max Meyer-Marcotty, MD, Clinic for Plastic, Reconstructive, and Aesthetic Surgery/Hand Surgery in Lüdenscheid, Germany.

"Even over a long-term follow-up, the transfer of fatty tissue to arthritic fingers joints appears to provide a safe and minimally invasive alternative to conventional surgery for patients with osteoarthritis.”

In the lipofilling procedure, Meyer-Marcotty and his colleagues used liposuction to take a small sample of each patient's fatty tissue from their upper thigh or hip area. The autologous fat was then injected into their arthritic finger joints. Patients wore a splint around the treated fingers and took pain relievers for a week. There were no infections or other complications reported.

The researchers followed outcomes in 25 finger joints for an average of 44 months after treatment, and found that pain scores fell from a median of 6 (on a 10-point scale) before treatment to just 0.5 points at follow-up. Grip strength of the treated fingers approximately doubled, while fist closure and hand function performing everyday tasks also improved.

“Even after a follow-up examination period of 44 months, the transfer of fatty tissue to arthritic finger joints has shown itself to be a minimally invasive, safe, and promising alternative to conventional surgical techniques aimed at alleviating arthritic complaints, and one that among other things entails a highly significant improvement in postsurgical pain levels,” researchers reported in the journal Plastic and Reconstructive Surgery. “Further long-term follow-up studies of even larger patient cohorts would be needed to further corroborate these initial positive findings.”

In recent years, lipofilling procedures have been increasingly used in plastic and reconstructive surgery, as well as stem cell therapy.

When injected into patients, mesenchymal stromal cells (MSCs) in fat tissue can regenerate damaged or diseased tissue, including cartilage in arthritic joints. A small 2019 study found that MSCs collected from a patient’s bone marrow can significantly reduce pain from knee osteoarthritis for up to a year.

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

"The chance to preserve the joint with a minimally invasive procedure is of particular interest in the early, albeit painful, phases of finger osteoarthritis," said Meyer-Marcotty. "Since the lipofilling procedure is nondestructive, conventional joint surgery can still be performed later, if needed."

FDA Approves Pain Reliever for Cats Considered Too Risky for Humans

By Pat Anson, PNN Editor

The U.S. Food and Drug Administration has approved a new medication to treat osteoarthritis pain in cats, the first monoclonal antibody drug approved by the FDA for use in any animal. The same type of drug has been rejected for use in humans because of safety risks.

Solensia (frunevetmab) is an injectable monoclonal antibody made by Zoetis that targets nerve growth factor (NGF), a protein that increases in animals and humans due to injury, inflammation or pain. Solensia is designed to bind to NGF and inhibit pain signals from reaching the brain.

Osteoarthritis (OA) is a progressive joint disorder that leads to thinning of cartilage and joint damage.  Feline OA is a common condition in older cats, but treatment options for them are limited, as they are for humans.

“Advancements in modern veterinary medicine have been instrumental in extending the lives of many animals, including cats. But with longer lives come chronic diseases, such as osteoarthritis," said Steven Solomon, DVM, director of the FDA's Center for Veterinary Medicine.

"Today's approval marks the first treatment option to help provide relief to cats that are suffering from this condition and may significantly improve their quality of life. We also hope that today's approval of the first monoclonal antibody by the FDA for any animal species will expand research and development of other monoclonal antibody products to treat animal diseases."

Safety Issues with NGF Inhibitors

Last year the FDA refused to approve tanezumab, a monoclonal antibody and NGF inhibitor, as a treatment for OA in humans after two of its advisory panels said the drug caused OA joint damage to accelerate. Rapidly progressing osteoarthritis (RPOA) was so severe that some patients in clinical trials had to stop taking the drug and needed total joint replacements.

The side effects of NGF inhibitors have been known for over a decade. The FDA slowed the development of NGF inhibitors in 2010 because of concerns they make osteoarthritis worse in some patients. But under pressure to approve more non-opioid pain relievers, the FDA allowed clinical studies of tanezumab to resume in 2015.

Eli Lilly and Pfizer invested heavily in tanezumab research, but ended their joint development of the drug in 2021 after the FDA and European Medicines Agency said they would not approve tanezumab for humans because of safety concerns.

In a press release announcing the approval of Solensia for cats, the FDA makes no mention of RPOA in its list of side effects, which includes vomiting, diarrhea, injection site pain, scabbing, dermatitis and itchy skin. The release said side effects were mild and did not require ending treatment during observational animal studies.  

In the FDA’s more detailed Freedom of Information Summary for Solensia, the agency said “RPOA has not been characterized or reported in cats,” but has this stark warning for humans who administer the drug:

“Women who are pregnant, may become pregnant, or are breastfeeding should take extreme caution to avoid accidental self-injection of Solensia. It is well-established that NGF is important in the normal development of the fetal nervous system, and laboratory studies in nonhuman primates have shown that human anti-NGF mAbs can cause reproductive and developmental toxicity. Fetal abnormalities, increased rate of stillbirths, and increased postpartum fetal mortality were noted in rodents and nonhuman primates receiving anti-NGF mAbs.”

Solensia is not recommended for pregnant or lactating cats. It will only be available by prescription from a licensed veterinarian who administers the injection monthly.

“The approval of Solensia is a significant step forward in the control of feline OA pain. Cat owners and veterinarians alike can feel confident that Solensia, with active substance frunevetmab, a monoclonal antibody (mAb) designed specifically for felines, has been studied and demonstrated to control OA pain and help cats get back to moving more freely again,” Mike McFarland, DVM, Chief Medical Officer for Zoetis, said in a statement.

The use of Solensia in cats was approved by the European Medicines Agency last year. The drug is expected to be available to U.S. veterinarians in the second half of 2022.

One in Four U.S. Adults Have Arthritis

By Pat Anson, PNN Editor

Nearly one in four American adults --- 58.5 million people – report having arthritis, according to a new study by the CDC that highlights both the aging of the U.S. population and the challenges that poses for the nation’s healthcare system.

Arthritis is a disease that causes joint pain and stiffness, which typically worsen with age, and is the leading cause of adult disability. The most common types of arthritis are osteoarthritis and rheumatoid arthritis.

Researchers found that over half of Americans aged 65 and older have arthritis (50.4%); along with adults who are disabled or unable to work (52.3%); and adults who rate their health as either fair or poor (51.2%).

The national prevalence of disability linked to arthritis – what the CDC calls arthritis-attributable activity limitations (AAAL) – has been steadily rising for nearly two decades. The trend appears to be accelerating due to aging, rising levels of obesity and reduced physical activity. The CDC estimates nearly 26 million Americans had AAAL in 2016-2018.

SOURCE: CDC

"AAAL prevalence continues to increase more rapidly than was projected. Because population aging and other contributing factors (e.g., obesity) are expected to sustain these trends, public health, medical, and senior and other service systems face substantial challenges in addressing the needs of adults with arthritis, who already account for nearly one quarter of U.S. adults," researchers reported in the CDC’s Morbidity and Mortality Weekly Report.

To address the social, physical and economic challenges of arthritis, the report recommends an expansion of outreach programs to individuals and groups at high risk of arthritis. AAAL is common among adult American Indian or Alaskan Natives (60.7%); low income adults (53.3%); adults living near or below poverty levels (63.3%); disabled adults (82.6%); and those with serious psychological distress (76.3%).

“Existing self-management education and physical activity public health interventions that are arthritis-appropriate and inclusive of adults with disabilities have proven benefits, including improved aerobic activity, confidence, and self-rated health and reduced depression, fatigue, and pain. These positive effects might be bolstered by combination with medical management, particularly for joint symptoms and mental health,” researchers said.

One step arthritis sufferers can take to help themselves is to make greater use of the Americans with Disabilities Act (ADA), which is underused by people with rheumatic conditions. The ADA can help eliminate physical barriers and improve access to transportation, building access, and workplace accommodations. If you feel you've been discriminated against because of a disability, you can file a complaint with the U.S. Justice Department under the ADA.

The Job Accommodation Network is another free resource that can be used for confidential job counseling, employment advice, facilitation of workplace accommodations, and the resolution of disability-related employment issues.

Researchers Urge Caution on Using Steroid Injections for Pain

By Pat Anson, PNN Editor

Doctors and patients should be more cautious about using corticosteroid injections for pain relief, according to new studies that warn of rare, but serious long-term complications for patients who receive epidurals during childbirth or high doses and multiple injections in their hips.

Researchers at Kaiser Moanalua Medical Center in Hawaii looked at health data for nearly 700 patients with hip osteoarthritis and found that those who received steroid injections were 8.5 times more likely to develop rapidly destructive hip disease (RDHD), a condition that causes the loss of blood flow and death of bone tissue in the hip.

Higher rates of RDHD were especially apparent in patients receiving multiple and/or high-dose injections of the steroid triamcinolone. The risk of RDHD following a single, low-dose injection was about two percent, but rose to five percent following multiple low-dose injections or a single high-dose injection, and up to 10 percent following multiple high-dose injections.

“While the risk of RDHD following a single low-dose (40 mg or less) triamcinolone injection is low, the risk is higher following high-dose (80 mg or more) injection and multiple injections. These findings provide information that can be used to counsel patients about the risks associated with this common procedure. In addition, caution should be taken with intra-articular hip injections utilizing 80 mg of corticosteroid and multiple injections,” wrote lead author Kanu Okike, MD, of Hawaii Permanente Medical Group in Honolulu.

As they became more aware of a possible link with RDHD, orthopedic surgeons at the hospital started ordering fewer hip corticosteroid injections. In subsequent years, the number of RDHD cases decreased. The hospital also added a discussion of post-injection RDHD to the informed consent process for patients and stopped performing high-dose corticosteroid injections.

The study, recently published in The Journal of Bone & Joint Surgery, is believed to be the largest to date of patients with post-injection RDHD.

Epidural Injections

Two new studies have also found that women receiving epidural injections for pain relief during labor are at high risk of long-term headaches and chronic back pain if the needle accidentally punctures the dural lining of the spinal cord. Dural punctures or “wet taps” cause the leak of spinal fluid, which can result in serious neurological complications.  

“I’ve likely performed more than 10,000 epidurals in my lifetime, and I still have wet taps from time to time,” Pamela Flood, MD, a professor of anesthesiology at Stanford University School of Medicine, told Anesthesiology News. “But no matter how many we’ve seen, we still feel terrible about each one. We’re trying to relieve people’s pain and give them a wonderful childbirth experience, and the last thing we want to do is cause them complications.”

A study published in the journal Anaesthesia found that over half of women (58%) with an accidental dural puncture were still experiencing headaches 18 months after the epidural, and nearly half (48%) suffered from chronic low back pain. A recent study in the British Journal of Anaesthesia had similar findings.    

Dural punctures during epidurals are relatively uncommon. Women are usually warned there is a risk of short-term headaches, but not about long-term health problems.

“While this information has been creeping into our consciousness in the form of retrospective trials, only this year has it been confirmed with two large prospective trials,” Flood said. “Unfortunately, clinicians have been slow to hear this, perhaps because we don’t want to admit that the short-term concern that we have been discussing for years carries long-term consequences in a significant percentage of women.”

The two most common types of medications used during epidural injections are anesthetics (lidocaine or bupivacaine) or corticosteroids (betamethasone, dexamethasone, hydrocortisone, methyl-prednisolone, triamcinolone). 

In addition to treating labor pain, epidural steroid injections are widely used for back pain. About 9 million epidural steroid injections are performed annually in the U.S., even though they are not FDA-approved. The FDA has warned that injection of steroids into the epidural space can result in rare but serious neurological problems, including loss of vision, stroke and paralysis. Some patients have also developed arachnoiditis, a chronic and painful inflammation of the spinal cord, after getting steroid injections for back pain.

Experimental Implant Repairs Joints With Cartilage Made From Stem Cells

By Pat Anson, PNN Editor

An experimental implant containing cartilage derived from stem cells reduced pain and restored function in dogs with damaged hip joints -- a study that researchers say could be a significant step towards repairing and replacing cartilage in humans with osteoarthritis.

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.

“One of the holy grails of orthopedics is to replace cartilage, but there hasn’t been an effective way to do it,” says co-author Duncan Lascelles, PhD, a professor of surgery and translational pain research and management at North Carolina State. “Most of the focus is on replacing or restoring the cartilage surface with artificial materials, but regenerating cartilage isn’t possible right now. And many of the artificial products in use don’t integrate with the body.”

Lascelles and his colleagues developed a cartilage repair implant using a textile manufacturing process that utilizes three-dimensional (3D) weaving with composite material. When seeded with a patient’s own stem cells, the “bioartificial” implant is designed to integrate with native bone while preserving the integrity of the joint.

“Combining 3D printing with advanced textiles enabled us to engineer an implant that mimics the function of native, healthy tissues in the joint from day one after implantation,” said co-author Bradley Estes, PhD, President of Cytex Therapeutics, which developed the implant technology. “We also designed it to dissolve over time so that, ultimately, joint function is transferred back to the patient’s own tissues during the healing process.”

The researchers used the implant to resurface damaged hip joints in dogs. Cartilage derived from stem cells was first allowed to grow on the implant for several weeks before surgery, then the implant was placed into the damaged area of the dogs’ joints. Over time, the implant dissolved, leaving only the dog’s own natural tissue in the repaired hip joint.

Four months after surgery, researchers say dogs that received the cartilage implant returned to baseline levels for both pain and function, while dogs in a control group never improved. They also saw evidence that the implant had successfully integrated into the hip joints, effectively resurfacing them.

“We were thrilled that the implant was so effective at restoring the activity levels of the animals,” Estes says. “After all, this is why patients go see their physicians – they want to be able to play tennis, play with their kids, and, in general, re-engage in a pain-free active lifestyle that had been taken away by arthritis.”

While osteoarthritis primarily affects older adults, researchers hope the experimental implant will address some of the problems associated with total joint replacements in younger, active patients.

“There are significant drawbacks to total joint replacements in the young patient,” Lascelles says. “The surgery is more complicated, and the artificial joints are only good for a particular number of years until they must be replaced, often with poorer results each time.

“This procedure is less invasive, and the implant uses the body’s own cells and integrates into the damaged area with little danger of rejection. We believe that it is an early intervention that could be a major advance in postponing joint replacements for dogs and hopefully one day for humans.”

The research findings are published online in Science Advances. The study was funded by Shriners Hospitals for Children, the Arthritis Foundation, the Nancy Taylor Foundation for Chronic Diseases, and the National Institutes of Health.

Blood Pressure Meds May Help Treat Osteoarthritis

By Pat Anson, PNN Editor

People who suffer from osteoarthritis have few pain-relieving options outside of surgery and joint replacement. Opioids are usually not prescribed for osteoarthritis (OA) and over-the-counter drugs such as acetaminophen provide only mild relief or may have side effects if taken too often.

Some OA patients may have another treatment option already sitting in their medicine cabinets: blood pressure medication.

In a retrospective study, researchers at the University of Nottingham analyzed health data for over 223,000 people in the UK and found that patients taking two beta-blockers commonly prescribed for high blood pressure -- propranolol and atenolol -- made fewer trips to the doctor to be treated for knee and hip pain compared to those who don’t use the drugs. When patients stopped taking propranolol and atenolol, they had more office visits for joint pain.

The findings, recently published in the journal Rheumatology, suggest that beta-blockers have analgesic properties and may even slow the progression of osteoarthritis, a joint disorder that leads to thinning of cartilage in the knees, hips, fingers and spine. About 10% of men and 18% of women over age 60 have some form of osteoarthritis. .  

"Our findings suggest that atenolol could be considered for people with osteoarthritis and comorbidities for which beta blockers are indicated," co-authors Georgina Nakafero, PhD, and Abhishek Abhishek, PhD, said in a news release. "Similarly, propranolol may be a suitable analgesic for people with OA and comorbid anxiety.

"If these findings are confirmed in independent studies, and in a confirmatory randomized controlled trial, it may change clinical practice."

Previous research has suggested that beta-blockers have antinociceptive effects that help block pain signals. A 2017 study found the drugs lowered pain scores and reduced opioid use in 873 patients with OA. But a larger study failed to confirm those findings.

Two FDA advisory committees recently voted against recommending tanezumab, an experimental non-opioid pain reliever, as a treatment for osteoarthritis due to possible side effects. The agency has yet to make a final decision on the drug. If approved, tanezumab would be the first new class of medication for osteoarthritis in well over a decade.

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.

FDA Panels Say New Arthritis Drug Too Risky

By Pat Anson, PNN Editor

Two FDA advisory committees have voted against recommending an experimental non-opioid pain reliever as a new treatment for osteoarthritis, dealing a potential death blow to a drug that’s been under development for 15 years.

On a nearly unanimous 19 to 1 vote, the FDA’s Arthritis Advisory Commitee and Drug Safety and Risk Management Advisory Committee decided that the benefits of tanezumab do not outweigh its possible safety risks, which include the acceleration of osteoarthritis in some patients.  Advisory committee recommendations are not binding on the FDA, but they are likely to carry a good deal of weight when the agency makes a final decision on tanezumab.

Pfizer and Eli Lilly are jointly developing tanezumab, an injectable humanized monoclonal antibody that targets nerve growth factor (NGF), a protein that increases in the body due to injury, inflammation or chronic pain. Tanezumab binds to NGF and inhibits pain signals from muscles, skin and organs from reaching the brain.

FDA reviewers released a report this week saying tanezumab works as a pain reliever, but the effect “is modest, and there is no convincing evidence of a superior efficacy” over non-steroidal anti-inflammatory drugs (NSAIDs), the current standard treatment for osteoarthritis.

More concerning are the potential side effects of tanezumab, the most serious being rapidly progressing osteoarthritis that is so severe some patients need total joint replacements. Investigators say tanezumab also appears to affect healthy joints and causes “abnormal peripheral sensation” similar to carpal tunnel syndrome.

The side effects of tanezumab have been known for over a decade. The FDA slowed the development of tanezumab and other NGF inhibitors in 2010 because of concerns they make osteoarthritis worse in some patients.

Under pressure to approve more non-opioid pain relievers, the FDA allowed clinical studies of tanezumab to resume in 2015 and two years later gave it “fast track” designation to help speed its development.

Pfizer and Eli Lilly have conducted dozens of clinical trials evaluating the safety and efficacy of tanezumab on more than 18,000 patients. The companies at one time considered, but then abandoned plans to develop tanezumab as a treatment for chronic low back pain after 10% of patients given high doses developed joint pain and other side effects.

Critics say its time to finally throw in the towel on tanezumab.

“The drug is unsafe. It accelerates the underlying joint disease. And according to the FDA, even if you stop the drug early on, there’s evidence you can still progress to having these joint problems,” Michael Carome, director of Public Citizen’s Health Research Group, told PNN.  “The decision here is clear cut. The drug should not be approved. And in our view, no further studies on this drug should be done. Because it would be unethical to continue to expose people to this drug where the harm is clear and there’s no real benefit.”

A Pfizer spokesman said the company would continue to seek approval for tanezumab, despite the committees’ recommendation.

“While we are disappointed in today’s outcome, we continue to believe that the clinical data presented for tanezumab supports its benefit-risk profile,” Jim Rusnak, chief development officer for Pfizer, said in a statement. “The patients whom we aim to help with tanezumab are suffering from significant, debilitating osteoarthritis pain and have exhausted available medical therapies and are hopeful for new, non-opioid treatments. We will continue to work with the FDA to determine next steps.”

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

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.”

Antidepressants Ineffective for Back Pain and Osteoarthritis

By Pat Anson, PNN Editor

Antidepressants like duloxetine (Cymbalta) are increasingly being prescribed to treat various types of pain, but a new study shows the medications are largely ineffective for people suffering from chronic back pain or osteoarthritis and may even cause harm.

Many clinical guidelines recommend using antidepressants as pain relievers – even when depression is not involved -- yet evidence supporting that use is uncertain. To address that knowledge gap, researchers at the University of Sydney reviewed data from 33 controlled trials involving more than 5,000 adults who took antidepressants for low back or neck pain, sciatica, or hip or knee osteoarthritis.

Their findings, published in The BMJ, show that for people with back pain the effects of antidepressants were too small to be worthwhile, but for those with osteoarthritis there may be a small beneficial effect.

“The use of antidepressants to treat people with chronic back pain and osteoarthritis is increasing worldwide, but prior to our work, it was not clear whether antidepressants relieved pain or were safe,” said lead author Dr. Giovanni Ferreira, PhD, a postdoctoral research fellow at the Institute for Musculoskeletal Health at the University of Sydney. 

“We conducted a review of all randomised clinical trials evaluating the efficacy of antidepressants for people with back pain or knee osteoarthritis and found that for back pain the antidepressants were either ineffective or provided a very small effect, which was unlikely to be perceived as worthwhile by most patients. For people with osteoarthritis, effects were still small, but could be potentially perceived as worthwhile by some patients” 

Ferreira and his colleagues reviewed six classes of antidepressants: serotonin-noradrenaline reuptake inhibitors (SNRIs); selective serotonin reuptake inhibitors (SSRIs); noradrenaline-dopamine reuptake inhibitors (NDRIs); tricyclic antidepressants; and tetracyclic antidepressants. 

Results showed that SNRIs such as duloxetine reduced back pain after three months, but the benefits were so small they were unlikely to be considered clinically important to most patients. SNRIs had a slightly stronger effect on sciatica and osteoarthritis pain. 

Tricyclic antidepressants were ineffective for back pain, but might reduce pain in people with sciatica, although the evidence for that was weak.  

Industry Funded Studies 

Importantly, about two-thirds of people taking SNRI antidepressants experienced an adverse event such as nausea, fatigue, mood swings and weight gain.

“Many people are being treated with these medications that may not be helping their pain and may be doing them harm,” said Ferreira, adding that doctors need to be upfront with patients about possible side effects.

Researchers say the long-term effects of antidepressants prescribed for chronic pain are not well known and many of the studies that do exist were sponsored by industry, raising the risk of bias. 

“Many people are being treated with these medications that may not be helping their pain and may be doing them harm.”

— Dr. Giovanni Ferreira

“Large, definitive trials free of industry ties are urgently needed to evaluate the efficacy of antidepressants,” Ferreira said. “There needs to be more transparency about how evidence coming from those trials is appraised by guideline panels. A good starting point would be to consider all industry-funded trials to be at high risk of bias, and downgrade the strength of recommendations where industry-sponsored trials represent an important part of the available evidence.”

The Food and Drug Administration recently approved duloxetine as a treatment for fibromyalgia in pediatric patients, largely on the basis of a small trial conducted by Eli Lilly, Cymbalta’s manufacturer. Children enrolled in the study did show a modest improvement in pain, but several of them had serious adverse events, including two attempted suicides, suicidal thoughts, an intentional drug overdose, depression and hallucinations.

In their published findings in the journal Pediatric Rheumatology, Eli Lilly researchers downplayed the adverse events associated with duloxetine, saying they were not drug related or “not significantly different” than those of children on placebo. The two attempted suicides aren’t even mentioned.

A common complaint of patients who take duloxetine is how quickly they become dependent and what happens when they stop taking the drug. Many complain of severe withdrawal symptoms, including electric-like sensations called “brain zaps.”

Duloxetine’s checkered history is well known at the FDA. The agency’s adverse events reporting system has recorded nearly 35,000 cases involving duloxetine since 2007, most of them classified as psychiatric disorders. Over 4,000 of those adverse events resulted in death.

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.