Diagnosing osteoarthritis often occurs in the late stages when cartilage degradation is severe, making it difficult to distinguish it from other types of arthritis and to determine the best treatment plan. In work published in the Journal of Orthopaedic Research, investigators have developed and tested a new diagnostic test that uses two markers found in the synovial fluid of patients’ joints.
After assessing levels of cartilage oligomeric matrix protein and interleukin‐8, the team came up with an algorithm based on the ratio of these two markers and validated its efficacy in differentiating osteoarthritis from inflammatory arthritis in 171 human knee synovial fluid specimens.
“This study addresses an unmet need for objective diagnosis of osteoarthritis to improve clinical decision-making and patient outcomes,” said corresponding author Daniel Keter, BA, of CD Diagnostics, A Division of Zimmer Biomet.
A new study published in the journal Osteoarthritis and Cartilage has found that people with newly diagnosed osteoarthritis (OA) of the knee or hip with contraindications to or precautions for NSAIDs still continue to be prescribed these drugs. Additionally they had higher use of opioids and slightly lower physical therapy (PT) use within the first year of OA diagnosis, both of which are not consistent with treatment guidelines for OA.
“We found individuals with contraindications to NSAIDs were still commonly prescribed them, placing them at risk for NSAID-related adverse events,” explains corresponding author Tuhina Neogi, MD, PhD, the Alan S. Cohen Professor of Rheumatology and professor of medicine at the school. “Additionally, they were not more likely to receive safer alternatives like PT despite its widespread recommendation as first-line intervention.”
The researchers used population-based register data to identify adults residing in Sweden (between 2004-13) without a previous knee or hip OA diagnosis. Among this group, between 2014-18, they identified people with knee or hip OA diagnosis and presence of contraindications to or precautions for oral NSAIDs at the time of OA diagnosis. They then estimated the risk of: 1) regular oral NSAID use; 2) regular opioid use; 3) PT during the first year after diagnosis among those with versus without contraindications or precautions.
Despite having contraindications to NSAIDs, 21% of those in the study were regular users of NSAIDs within the first year of their OA diagnosis. Similarly, 21% of those with precautions for using NSAIDs were also regular users. They also found a higher proportion of persons with contraindications were regular users of opioids than those without a contraindication or precaution, while a slightly lower proportion received PT.
Neogi stresses that more options for effective and safe management of OA symptoms are urgently needed, and greater work is required in narrowing and ultimately closing the evidence-knowledge-practice gap.
Yale researchers report in the journal Nature that they have identified a drug target that may alleviate joint degeneration associated with osteoarthritis.
The most common therapies for the degenerative disease have been pain relievers and lifestyle changes, to reduce pain and stiffness, but there is a pressing need for therapies that can prevent joint breakdown that occurs in osteoarthritis, which occurs as a result of the breakdown of cartilage in the joints.
Sodium channels found in cell membranes produce electrical impulses in “excitable” cells within muscles, the nervous system, and the heart. And in previous research, Yale’s Stephen G. Waxman identified the key role of one particular sodium channel, called Nav1.7, in the transmission of pain signals.
Now, the labs of Chuan-Ju Liu, professor of orthopaedics, and Waxman, professor neurology, neuroscience and pharmacology, have found that the same Nav1.7 channels are also present in non-excitable cells that produce collagen and help maintain the joints in the body. These channels can be targeted by existing drugs to block them.
In the new study, the researchers deleted Nav1.7 genes from these collagen-producing cells and significantly reduced joint damage in two osteoarthritis models in mice.
They also demonstrated that drugs used to block Nav1.7 – including carbamazepine, a sodium channel blocker currently used to treat epilepsy and trigeminal neuralgia – also provided substantial protection from joint damage in the mice.
“The function of sodium channels in non-excitable cells has been a mystery,” Waxman said.
“This new study provides a window on how small numbers of sodium channels can powerfully regulate the behaviour of non-excitable cells.”
“The findings open new avenues for disease-modifying treatments,” added Wenyu Fu, a research scientist in the Liu laboratory and first author of the study.
Besides its significant impact on disability, symptomatic OA is associated with an increased risk of all-cause mortality. Current guidelines advise weight loss to improve function and reduce pain but there is little data on whether it also reduces mortality risk.
New research published in Arthritis & Rheumatology suggests that for people overweight or with obesity and also knee or hip osteoarthritis, a slow-to-moderate – but not fast – rate of weight loss caused by anti-obesity medications may lower their risk of premature death.
Researchers enrolled 6524 participants with knee or hip osteoarthritis who were taking orlistat, sibutramine, or rimonabant to the study. The five-year death rate was 5.3%, 4.0%, and 5.4% for the “weight gain/stable”, “slow-to-moderate weight loss,” and “fast weight loss” groups, respectively. Compared with the “weight gain/stable” group,” the risk of death was 28% lower for the “slow-to-moderate weight loss” group and only 1% lower for the “fast weight loss” arm.
“A slow-to-moderate rate of weight loss induced by anti-obesity medications may lower the risk of death in overweight/obese people with knee/hip osteoarthritis”, said first author Jie Wei, PhD, of Xiangya Hospital, Central South University, in China.
Relief could be on the way for people with painful hand osteoarthritis after a new study found an affordable existing drug can help. Until now there has been no effective treatment.
Published in The Lancet, the paper investigated methotrexate, a low-cost, effective treatment for inflammatory joint conditions such as rheumatoid arthritis and psoriatic arthritis. It has been widely used in Australia and globally since the early 1980s.
Researchers led by Monash University and Alfred Health found that methotrexate reduced symptoms in those with hand osteoarthritis (OA). A 20mg weekly oral dose over six months had a moderate effect in reducing pain and stiffness in patients with symptomatic hand OA.
Hand OA is a disabling condition that causes pain and affects function, impeding daily activities such as dressing and eating. It can significantly reduce quality of life. About one in two women and one in four men will experience symptoms from hand OA by the time they turn 85.
About half will have inflamed joints, which cause pain and are associated with significant joint damage. Despite the high prevalence and disease burden, there are no effective medications.
Senior author Professor Flavia Cicuttini said that the study identified the role of inflammation in hand OA and the potential benefit of targeting patients who experience painful hand OA.
“In our study, as with most studies of osteoarthritis, both the placebo group and methotrexate groups’ pain improved in the first month or so,” Professor Cicuttini said.
“However, pain levels stayed the same in the placebo group but continued to decrease in the methotrexate group at three and six months, when they were still decreasing. The pain improvement in the methotrexate group was twice as much as in the placebo group.
“Based on these results, use of methotrexate can be considered in the management of hand osteoarthritis with an inflammatory pattern. This provides clinicians with a treatment option for this group, which tends to get more joint damage.”
Professor Cicuttini said in patients with hand OA and inflammation, the effects of methotrexate were present at about three months and by six months it was very clear if it worked.
“At that time patients and their doctors can decide whether to continue or stop it,” she said. “This is very similar to what we currently do with other forms of inflammatory arthritis.”
The randomised, double-blind, placebo-controlled trial of 97 people with hand OA and MRI-detected inflammation assessed whether 20mg of methotrexate weekly reduced pain and improved function compared to placebo in patients with symptomatic hand OA and synovitis (inflammation) over six months.
Professor Cicuttini said the results could provide relief for people with hand OA inflammation, which was particularly common in women as they experienced menopause.
“Further trials are needed to establish whether the effect of methotrexate extends beyond six months, for how long we need to treat patients, and whether methotrexate reduces joint damage in patients with hand osteoarthritis and associated inflammation,” she said.
Professor Cicuttini now plans to conduct an extension trial to address these questions, in particular whether women who develop hand OA around menopause and often have severe pain and joint damage may benefit.
Photo by Towfiqu barbhuiya: https://www.pexels.com/photo/person-feeling-pain-in-the-knee-11349880/
Although osteoarthritis has been extensively studied through a medical perspective, the molecular changes associated with osteoarthritis remain unclear. New research published in Biointerphases suggests that there may be an optimum concentration and size of molecules in the synovial fluid needed to form the protective film in joints.
Osteoarthritis is the most common degenerative joint disease, affecting 22% of adults over 40 globally. The cartilage in the joints, in concert with the synovial fluid, provides a smooth surface to support weight-bearing movements. The fluid contains several molecules, including hyaluronan (HA) and phospholipids. Since the cartilage environment cannot be quickly healed or repaired, researchers have tried to diagnose the early stages of joint disease by monitoring the molecular weight and concentration of HA.
“Although we know that in healthy joints there is very low friction, it is unclear which other molecules are involved and how they change during osteoarthritis,” said Rosa Espinosa-Marzal (EIRH), professor of environmental engineering & science, and materials science & engineering. “During the early stages of osteoarthritis, cartilage starts degrading, and previous research has shown that the molecular composition of the synovial fluid changes. We wanted to see if the two changes are related to each other.”
In a healthy joint, the molecular weight of HA varies between 2–20 MDa with a concentration ranging from 1–4 mg/mL. Studies have shown that in diseased joints, HA is broken down resulting in a lower molecular weight and its concentration is also reduced by 10x. Based on these observations, made by other researchers, the study looked at how the concentration and molecular weight of HA influences the structure of healthy and diseased joints.
To do so, the researchers combined vesicles with high and low molecular weight HA. Using neutron scattering and light scattering, they discovered that the molecular weight of HA can vastly change the structure of the vesicles. Lower molecular weight HA, which mimics osteoarthritis-diseased joints, results in larger vesicle size. Changes in HA’s molecular weight also changed the thickness of the phospholipid layers in the joints.
The researchers also studied how these differences can influence the formation of a protective film; in joints this film is responsible for the very low friction we need for unhindered motion. Once again, they used a combination of techniques, quartz crystal microbalance and atomic force microscopy, to examine how these molecules assemble on gold surfaces.
“The formation of a film is possible only when there is an optimal concentration of HA and phospholipids. Even though the gold surfaces have very little in common with cartilage, our studies indicate that there could also be an optimum concentration under biological conditions,” Espinosa-Marzal said. “This is an important observation because we can use the concentration changes as a diagnostic tool.”
The researchers are now testing this theory using cartilage. They are also interested in studying the other molecular components that are found in joints to build a more comprehensive model of the changes that are associated with osteoarthritis.
A new joint health supplement has been launched in South Africa by iNOVA Pharmaceuticals which supports healthy joints and helps reduce the symptoms of osteoarthritis such as joint pain and stiffness1. Unlike other osteoarthritis supplements on the market, POSTEON™ has been shown to start working in as little as five days1.
According to scientifically based research, the ingredients in Posteon™ may help reduce the symptoms of osteoarthritis such as joint pain and stiffness, as well as improving range of motion and mobility1.
Boswellia serrata gum resin extract has traditionally been used to relieve symptoms of osteoarthritis. Taken once a day, Posteon™ contains 100mg of 3-O-Acetyl-11-keto-beta- boswellic acid (AKBA), the most active compound of Boswellia extract which is an inhibitor of 5-lipoxygenase (5-LOX). This is a key enzyme in the biosynthesis of leukotrienes from arachidonic acid in the cellular inflammatory cascade1.
It also contains 300mg of Avocado soy unsaponifiables (ASU), a dietary supplement consisting of one-third avocado oil and two-thirds soybean oil. Studies have found that ASU can reduce the production/action of various joint inflammatory substances which can prevent the destruction of joint cartilage and also help in its repair1.
Osteoarthritis is the most common form of arthritis2 and affects between 55.1% and as many as 82.7% of adults aged over 65 years in South Africa3. Globally, the prevalence of osteoarthritis is increasing, and is expected to continue to escalate4.
POSTEON™, which is now available at leading pharmacies, may reduce these symptoms1 which can significantly impact day-to-day functioning2.
Usenbo, A et al. Prevalence of Arthritis in Africa: A Systematic Review and Meta-Analysis. A Systematic Review of Arthritis Prevalence in Africa (2015) at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4524637/ (website accessed on 4 May 2023).
Osteoarthritis Research Society International (OARSI) Osteoarthritis: A Serious Disease, Submitted to the U.S. Food and Drug Administration (2016) at https://oarsi.org/oarsi-white-paper-oa-serious-disease (website accessed on 4 May 2023).
DISCLAIMER: This editorial has been commissioned and brought to you by iNova Pharmaceuticals.
Content in this editorial is for general information only and is not intended to provide medical or other professional advice. For more information on your medical condition and treatment options, speak to your healthcare professional.
The composition of synovial fluid changes significantly in osteoarthritis: The concentration and molecular weight of hyaluronic acid tends to decrease and is commonly used to diagnose the disease. An international group of researchers explored the disease-driven breakdown of hyaluronan and the mechanistic implications of these changes on the lubrication and subsequent wear of joints.
“One of the most important properties of the synovial fluid is its viscosity,” said Rosa Maria Espinosa-Marzal, co-author of the study published in the journal Biointerphases. “Viscosity is a measure of the internal frictional force between adjacent layers of a fluid in relative motion, or, more simply, a fluid’s resistance to flow. Large, high molecular weight polymers such as hyaluronic acid play a significant role in maintaining a high viscosity of the synovial fluid, which helps maintain a fluid film and reduces friction between articulating surfaces during motion.”
Through analysis with neutron and light scattering, the team determined that the structure of the lipid-hyaluronic-acid complexes in the bulk solution is a function of concentration and its molecular weight.
The researchers found the hyaluronic acid’s concentration and molecular weight both play a role in how the lubricant reacts with different surfaces.
“Our results show low molecular weight hyaluronic acid, which mimics osteoarthritis-diseased joints, hinders the adsorption of the hyaluronic-acid-lipid complex,” said Espinosa-Marzal, of the University of Illinois Urbana-Champaign. “The lack of the formation of an amorphous film on the surface may reflect a consequence of osteoarthritis, since this film should help reduce friction and wear.”
Their hypothesis is that this film’s absence may increase wear of the cartilage surface. In contrast, high molecular weight hyaluronic-acid-lipid complexes form an amorphous film, which presumably helps maintain the mechanical integrity and longevity of efficient lubrication in healthy cartilage.
Studies on hyaluronic acid itself and hyaluronic-acid-lipid complexes “do not entirely support hyaluronic acid’s role in providing high lubricity to the cartilage’s articular surface, which is still a bit controversial,” Espinosa-Marzal said. “Our results indicate that for low molecular weight hyaluronic acid, this is likely the case.”
By exploring the complex interplay between phospholipid and hyaluronic acid self-assembly, and the role of molecular weight on surface affinity, “our study illuminates a mechanism whereby the ‘vicious circle’ of osteoarthritis can be explained,” said co-author Mark Rutland, from KTH Royal Institute of Technology.
Treating knee osteoarthritis with hyaluronic acid injections (known as viscosupplementation) makes almost no difference to pain or functioning and might raise risk of adverse events, suggests a review of 50 years of literature on the procedure.
Viscosupplementation has been used to treat knee osteoarthritis since the 1970s, but there are long-standing questions over its safety and efficacy.
Some 560 million people worldwide suffer from knee osteoarthritis, which involves inflammation and structural changes of the joints, resulting in joint pain and limitations to physical movement.
National and international guidelines vary in their recommendations, but most advise against the use of viscosupplementation. Researchers therefore set out to review 50 years’ worth of studies to evaluate the safety and efficacy of viscosupplementation. The studies compared viscosupplementation to placebo or no treatment.
Published in The BMJ, the main analysis of this review found that viscosupplementation was associated with a small reduction in pain compared with placebo, but the difference was tiny and was described as “clinically irrelevant.”
Their analysis showed that since 2009, there has been conclusive evidence that viscosupplementation and placebo treatment have led to the same clinical result in terms of pain reduction, meaning there is no point to having the injections.
They also found from 15 large trials on 6462 randomised participants that viscosupplementation was linked to a 49% higher risk of serious adverse events than placebo.
The authors say that based on their analysis of the studies between 2009 and 2021 alone, more than 12 000 patients were arguably unnecessarily subjected to these injections in viscosupplementation trials, which raises ethical concerns.
The study has some limitations in that it represents summary estimates and does not necessarily exclude the possibility that selected patient populations could benefit from viscosupplementation. Also, the researchers looked at adverse events that emerged rather than adverse events directly and clearly related to treatment.
However, strengths include the fact that this is the largest collection of randomised trials on viscosupplementation reported to date, which significantly decreases the risk of bias influencing the results.
As such, the authors conclude: “There is strong, conclusive evidence that among patients with knee osteoarthritis, viscosupplementation, compared with placebo, is associated with a clinically irrelevant reduction in pain intensity and with an increased risk of serious adverse events.
“The findings do not support broad use of viscosupplementation for the treatment of knee osteoarthritis.”
For patients with painful finger osteoarthritis, lipofilling a nonsurgical procedure where a patient’s fat is transferred into the arthritic joints, may result in lasting improvements in hand function and especially pain, according to a study in Plastic and Reconstructive Surgery.
Researchers reported their experience with 18 patients undergoing fat transfer procedures for finger osteoarthritis.
“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,” commented the study’s lead author Max Meyer-Marcotty, MD, PhD.
In the lipofilling procedure, a sample of the patient’s own fatty tissue was obtained by liposuction from another part of the body: the upper thigh or hip area. Tiny volumes of lipid cells (< 1mL) were injected into the arthritic finger joints. For recovery, patients wore a splint around the treated finger and took pain relievers for a week. No infections or other complications were recorded.
The researchers analysed follow-up outcomes in a total of 25 finger joints treated by lipofilling. Hand function, pain scores, and patient satisfaction were evaluated an average of 44 months (maximum 50 months) after treatment.
Assessment showed a “highly significant clear improvement” in pain score: from a median of 6 points (on a 10-point scale) before treatment to 0.5 points at follow-up. “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,” Dr Meyer-Marcotty et al. wrote.
On functional evaluation, pinch grip strength of the treated fingers increased from a median of 2.0kg before lipofilling to 4.3kg at follow-up. Non-significant improvements were seen in fist closure force and score on a standard assessment of hand function during everyday tasks.
In severe cases of osteoarthritis, surgery is effective in relieving arthritis pain, but is associated with potential complications and lengthy recovery time.
Fat transfer procedures have been introduced in recent years for a growing range of purposes in plastic and reconstructive surgery. Animal studies have suggested that mesenchymal stromal cells found in fatty tissues can regenerate tissue in arthritic joints.
“The chance to preserve the joint with a minimally invasive procedure is of particular interest in the early, albeit painful, phases of finger osteoarthritis,” Dr. Meyer-Marcotty added. “Since the lipofilling procedure is nondestructive, conventional joint surgery can still be performed later, if needed.”
Larger long-term follow-up studies are needed to further corroborate these initial positive findings, the researchers said.
