Unique Drug Delivery Technology
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Radiographic Findings Of Oa
- Joint space narrowing
- Advice on weight loss
- The first-line treatment for all patients with symptomatic knee osteoarthritis includes patient education and physiotherapy. A combination of supervised exercises and a home exercise program have been shown to have the best results. These benefits are lost after 6 months if the exercises are stopped.
- Weight loss is valuable in all stages of knee OA. It is indicated in patients with symptomatic OA with a body mass index greater than 25. The best recommendation to achieve weight loss is with diet control and low-impact aerobic exercise.
- Knee bracing in OA can be used. Offloading-type braces which shift the load away from the involved knee compartment. This can be effective when there is a valgus or varus deformity.
Other non-physiotherapy based interventions include pharmacological management:
Overview Of The Research Topic
The present special collection includes ten Original Articles, five narrative Reviews and one Systematic Review providing new insights on current and future therapeutic options for OA.
A large contribution has been provided on pre-clinical researches. In a study on human OA chondrocytes, Sanchez et al. investigated the effects of Zeel T , a multicomponent medicinal product composed of plant and organ extracts, known for its symptomatic effects in observational clinical studies. The authors showed that Ze14 significantly inhibited cartilage degradation, reducing metalloproteinases expression, and promoted chondrogenesis .
Along the same line, Baek et al. observed the protective effects of 3-Sialyllactose, a compound derived of human milk, against the oxidative stress and inflammation processes induced by IL-1, in SW1353 chondrocytic cells.
Selonsertib , an inhibitor of Apoptosis Signal-regulated kinase-1 , has been studied both in in vitro and in in vivo models by Yan et al. The results of the study showed that Ser markedly prevented the IL-1-induced inflammatory reaction, cartilage degradation and cell apoptosis in rat chondrocytes besides, intra-articular injection of Ser, in rat OA model, significantly alleviated the progression of the disease .
Ma et al. observed that vanillic acid, a monomer derived from chinese herbal medicines, was able to target NLRP3 inflammasome reducing synovitis in a rat model of knee OA.
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Fda Approves New Treatment For Chronic Knee Pain
What we’re changing is the wiring of the knee so we’re taking away the pain signal and interrupting it,” Dr. Amin Sandeep, a pain specialist at Rush University Medical Center in Chicago who performs the procedure, told NBC News.
One 2016 study compared Coolief to popular cortisone injections, with patients reporting greater, longer-lasting pain relief with the new treatment than injections. Coolief reduces pain for about to 6 to 12 months, depending on how fast the nerves in the knee regenerate.
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Osteoarthritis can affect any joint when the cartilage wears off over time, often striking big joints like the knee, causing pain, swelling and stiffness. According to the American Academy of Orthopedic Surgeons, nearly 10 million Americans had osteoarthritis of the knee in 2010.
The three current recommended approaches for knee arthritis pain are physical therapy, non-steroidal anti-inflammatory drugs such as ibuprofen and naproxen, or the opioid painkiller tramadol.
But those didn’t help Felicia McCloden, a 65-year-old grandmother from outside of Chicago. The excruciating pain in her right knee made simple tasks like grocery shopping impossible.
I had inflammation, swelling, and my knee was like the size of a golf ball, McCloden told NBC News. “The arthritis was so bad that I could barely step down without severe pain.
“I thought I was going to limp for the rest of my life,” she said.
Treatments Targeting Inflammatory Mediators And Pathways
It is now commonly accepted that OA has an inflammatory component that might be more dominant in specific patient subgroups and joint tissues. The release of various pro-inflammatory mediators like prostaglandins, cytokines, and chemokines has been demonstrated in numerous pre-clinical OA animal models and in patients74. Synovitis is a common feature of inflammatory OA, and technical progress in imaging technologies like ultrasound and MRI revealed synovitis in a large number of patients at different disease stages75,76. A plethora of triggers including aberrant mechanical forces, metabolic syndrome, increased age, and fragments of cartilage extracellular matrix or crystals might induce the release of these mediators from various responsive joint tissue cell types. A large number of recent review articles address cells and components of the innate immune system as the main drivers of OA inflammatory processes77,78. Non-steroidal anti-inflammatory drugs and glucocorticoids are commonly used to treat OA but are not optimal owing to moderate effectiveness and serious side-effects in long-term use79,80.
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Investigational Drugs Targeting Cartilage Metabolism
The characteristic sign of OA is cartilage destruction, so emerging drugs targeting the molecular mechanism of articular cartilage should be an attractive therapeutic strategy for OA. The research direction is mainly to delay cartilage destruction by anti-catabolic agents and stimulate cartilage development and repair by anabolic agents.
Targeting Peripheral Opioid Receptors
Opioids are effective analgesics but their use is limited due to serious adverse side effects like constipation, respiratory depression, tolerance, and dependence. Currently, new opioid receptor agonists with an improved safety profile targeting the µ, , and subtypes are in development. Selectively targeting the peripheral -OR might avoid side effects observed when drugs target the µ-OR. Cara Therapeutics developed the selective -OR agonist CR845 and evaluated its efficacy in knee and hip OA , reporting dose-dependent efficacy in the reduction of pain in hip OA over knee OA38 .
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How Is Oa Treated
There is no cure for OA, so doctors usually treat OA symptoms with a combination of therapies, which may include the following:
- Increasing physical activity
- Medications, including over-the-counter pain relievers and prescription drugs
- Supportive devices such as crutches or canes
In addition to these treatments, people can gain confidence in managing their OA with self-management strategies. These strategies help reduce pain and disability so people with osteoarthritis can pursue the activities that are important to them. These five simple and effective arthritis management strategies can help.
Physical Activity for Arthritis
Some people are concerned that physical activity will make their arthritis worse, but joint-friendly physical activity can actually improve arthritis pain, function, and quality of life.
Drugs Targeting Bone Cells
New therapeutic approaches include neutralization of cathepsin K, the major osteolytic protease released by osteoclasts. The small molecule cathepsin K inhibitor MIV-711 effectively attenuated joint pathology in a rabbit OA model66 and slowed bone and cartilage degeneration in a phase IIa multicenter trial of primary knee OA20. With 26 weeks duration, the study was relatively short, and MIV-711 did not reduce pain during this time . Denosumab, a monoclonal antibody directed against RANKL and thereby inhibiting osteoclastogenesis, is currently tested in erosive OA of interphalangeal finger joints and in knee OA , but results have not been published to date. Potential new targets to address subchondral bone include TGF, which is elevated in OA synovial fluid67. Systemic blocking of TGF prevented bone and cartilage degeneration in a rodent OA model68, but targeting this specific molecule needs to take into consideration the physiological role of TGF as a differentiation stimulus for chondrocyte precursor cells67. Furthermore, OA bone is targeted by anabolic therapies. Teriparatide, a synthetic parathyroid hormone, effectively reduced chondrocyte apoptosis and attenuated OA progression after i.a. application in a surgical rat OA model69. Its effectivity is currently being evaluated in a phase II trial of knee OA .
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Another Look At This Study Of Canakinumab
The reanalysis compares rates of hip or knee replacement due to osteoarthritis in those receiving canakinumab with rates among those who received a placebo. The study authors thought that since canakinumab reduces inflammation, it might help the inflammation found in the joints of people with osteoarthritis while also offering cardiovascular benefits.
Osteoarthritis has long been considered a wear-and-tear, age-related, and non-inflammatory form of joint disease. But over the last decade or so, research has demonstrated that some degree of inflammation occurs in osteoarthritis. So its not too much of a stretch to think a drug like canakinumab might be effective for osteoarthritis. This drug is already approved for a number of inflammatory conditions, including certain forms of pediatric arthritis.
The results of this new study surprised me: over about four years, those receiving canakinumab were at least 40% less likely to have a hip or knee replacement than those receiving placebo.
Monoclonal Antibodies Neutralizing Nerve Growth Factor
NGF is a neurotrophin that stimulates the growth of nociceptive nerve fibers and the expression of nociceptive cell surface receptors . Almost all structures in the joint are innervated with nociceptive nerve fibers, and elevated NGF levels may be sources of refractory knee pain in OA . NGF is therefore an attractive target for novel analgesic agents. Tanezumab, Fulranumab, and Fasinumab are monoclonal antibodies that specifically target NGF and inhibit binding to its receptors . Tanezumab is the most widely studied and has completed pivotal phase III clinical trials, and Fasinumab is in the midst of phase III clinical trials , while Janssen has discontinued the clinical development of Fulranumab, with no active trials being underway . The US FDA recently has granted fast-track certification for Tanezumab for the treatment of chronic pain in patients with OA or chronic low back pain, and Tanezumab is expected to be approved for clinical use soon.
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Extracellular Vesicles Derived From Stem Cells
Our literature search shows that stem cells, specifically autologous stem cells derived from bone marrow and adipose tissue , are preferred over other cell types for regenerative strategies. However, there is doubt among surgeons and researchers about whether or not stem cells are really the optimal tool for regenerative therapy.
How Can I Get Access To This Treatment
ACI is now available on the NHS. This means that more peopleacross the UK can access ACI and its benefits. However, it is only offered to specific patients, usually those with small areas of cartilage damage or early osteoarthritis, as set out by NICE guidelines. You can speak to your GP or consultant to find out more.
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Editorial Note On The Review Process
F1000 Faculty Reviews are commissioned from members of the prestigiousF1000 Faculty and are edited as a service to readers. In order to make these reviews as comprehensive and accessible as possible, the referees provide input before publication and only the final, revised version is published. The referees who approved the final version are listed with their names and affiliations but without their reports on earlier versions .
The referees who approved this article are:
- Frank Zaucke, Orthopaedic University Hospital Friedrichsheim gGmbh, Frankfurt, GermanyNo competing interests were disclosed.
- Andrew Pitsillides, Skeletal Biology Group, Department of Comparative Biomedical Sciences, Royal Veterinary College, University of London, London, NW1 0TU, UKNo competing interests were disclosed.
- Changhai Ding, Menzies Research Institute, University of Tasmania, Hobart, Tasmania, 7000, AustraliaNo competing interests were disclosed.
New Trends In Pharmacological Treatments For Osteoarthritis
- 1Department of Rheumatology, Guangzhou First Peoples Hospital, School of Medicine, South China University of Technology, Guangzhou, China
- 2Clinical Research Centre, Zhujiang Hospital, Southern Medical University, Guangzhou, China
- 3Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS, Australia
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Osteoarthritis: New Trial Drug Has Powerful Anti
A new drug that researchers are currently trialing to treat osteoarthritis can dampen the harmful effects of an overactive immune system while protecting its beneficial functions. The drug could, therefore, potentially treat rheumatoid arthritis, as well as other conditions resulting from inflammation.
The network of cells and signaling molecules that make up the bodys immune system are critical to our survival. In the time of COVID-19, this has perhaps never been clearer.
Yet the human immune system must maintain a delicate balance. If this balance tips over into overactivity, the immune system can be extremely harmful to the body.
Indeed, an overambitious immune system causes a raft of diseases. These include inflammatory bowel disease, multiple sclerosis, and some forms of arthritis, which the medical community groups as autoimmune disorders. Scientists usually consider osteoarthritis, in contrast, to be a disease of wear and tear, and they have only recently begun to understand the role of inflammation in its progression.
In a study that the journal Inflammopharmacology recently published, researchers from the University of Liverpool in the United Kingdom found that a new trial drug for osteoarthritis could help keep the immune system in check while ensuring that its protective functions remain intact.
Walking For Exercise May Actually Prevent The Progression Of Knee Osteoarthritis
Walking is widely recommended as low-impact exercise for people with knee osteoarthritis. It can also help with weight management, which is important for reducing stress on arthritic knees. Now research shows that people with knee arthritis who walk for exercise may actually have fewer painful symptoms and less structural damage over time.
Researchers studied 1,203 participants, taking X-rays of their knees at the start of the study and then four years later. About three-quarters of people said they walked for exercise. New knee pain was less common in people who walked and walking was associated with less structural progression of OA in patients with certain types of knee alignment.
The studys authors concluded that these findings support that walking for exercise should be encouraged for most people with knee OA.
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Knee Replacement Alternatives To Consider
Crunching sounds as you climb stairs, chronic aching and swelling: Knee osteoarthritis is a real pain. If youre suffering with it, you may be considering surgery.
Getting a knee replacement is one approach, but you may not need surgery, at least not right away. And some patients cannot undergo knee replacement surgery for various reasons. Other people with knee pain are too young for a knee replacement the artificial knee is only likely to last 15 or 20 years, after which the person may need revision surgery.
There are several things you can try first, on your own or with a professionals help, that can help with knee pain and even delay the need for replacement.
Arthritis doesnt go away, but there are things you can do to lessen the pain and stay more active.
Stopping Osteoarthritis: Could Recent Heart Research Provide A Clue
- By Robert H. Shmerling, MD, Senior Faculty Editor, Harvard Health Publishing
Heres a recent headline that I found confusing: Could the first drug that slows arthritis be here?
Its confusing because it depends on which of the more than 100 types of arthritis were discussing. Weve had drugs that slow rheumatoid arthritis for decades. In fact, more than a dozen FDA-approved drugs can reduce, or even halt, joint damage in people with rheumatoid arthritis. We also have effective medications to slow or stop gout, another common type of arthritis.
But the headline refers to osteoarthritis, the most common type of arthritis. And currently, no medications can safely and reliably slow the pace of this worsening joint disease. Thats one reason so many knee and hip replacements are performed: more than 1.2 million each year in the US alone.
A drug that can slow down joint degeneration in osteoarthritis has long been the holy grail of arthritis treatments, because it could
- relieve pain and lessen suffering for millions of people
- help prevent the loss of function that accompanies osteoarthritis
- reduce the need for surgery, along with its attendant risks, expense, and time needed for recovery.
And, needless to say, such a drug would generate enormous profits for the pharmaceutical company that comes up with it first.
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Dietary Supplementation Of Vitamin D3
Additional dietary supplementation of vitamin D3 might be an option to target and strengthen bone in OA owing to its ability to increase calcium and phosphate uptake from the gut and its direct effect on bone cell metabolism70. Numerous trials for vitamin D3 supplementation in OA patients can be found at clinicaltrials.gov, but there are contradictory reports about a relationship between vitamin D levels and a higher risk for OA incidence and progression71. A meta-analysis of randomized controlled trials revealed a reduction in WOMAC pain and improved joint function in OA patients after vitamin D3 intake, but only at a concentration of 2,000 IU72. Cartilage degradation was not affected. Generally, vitamin D3 intake might be beneficial for a large proportion of the population, as its deficiency is a worldwide problem and elderly people, who are also at an increased risk of OA, are often affected73.
Restoration of bone metabolism and structure might be a worthwhile goal because of the huge importance of this structure as a mechanic buffer for proper load perception and distribution. A detailed knowledge of timely changes in OA-related bone metabolism might enable a more precise use of bone anabolic and anti-catabolic therapies to restore or prevent bone degradation. Maintenance of bone structure and shock-absorbing abilities might prevent cartilage alterations and therefore put a hold on subsequent degradative events culminating in joint failure.
Bariatric Surgery Can Help Improve Knee Function And Delay Knee Replacement
Obesity is a known risk factor for osteoarthritis. Many people who are obese and require knee replacement surgery are counseled to lose weight first, which helps reduce the risk of post-surgery complications. However, weight loss is often difficult and bariatric surgery may be recommended.
A team of researchers is studying people who receive bariatric surgery to understand the impact on knee pain and function compared with obese patients who have knee replacement surgery without weight loss surgery first.
In initial findings, people who underwent bariatric surgery had comparable improvements in certain measures of pain and knee function compared with people who had knee replacement surgery. The researchers concluded that bariatric surgery may result in modest improvements in knee outcomes and may eventually delay the need for a .
Rheumatologist , Professor of Medicine in the Division of Rheumatology and Epidemiology and Biostatistics at the University of Western Ontario in Canada, said in a video on RheumNow that this research shows if you get bariatric surgery, your knee OA does improve a bit, so thats another benefit for those patients.
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