Physiotherapists And Knee Osteoarthritis

How consistent are physiotherapists in the advice they give to knee osteoarthritis patients?  It could be better, it seems.  The important message from the linked paper's abstract: 

Quality indicator compliance less than 50% was found for: education on the importance of weight loss, providing self-management strategies, spreading treatment session over longer periods and regular evaluations of the exercise therapy.

Less than 50% give advice for weight loss!  Shouldn't that be one of the first things one would say, given how many people in Belgium, where this study was conducted, are overweight?

Exercise For Hip Osteoarthritis

Can a specific exercise program enhance hip muscle strength and therefore be of benefit to patients suffering from hip osteoarthritis?  Here is a paper that says yes, abstract:

PURPOSE: To evaluate the effect of an exercise therapy concept (the Tübingen exercise therapy approach THüKo) for increasing hip muscle strength (HMS) in patients with hip osteoarthritis (OA), and to investigate whether patients do adhere to the intervention and if there are any adverse events related to the intervention.
METHODS: A total of 210 hip OA patients (89 females, 121 males) were randomized into a 12-week exercise intervention (THüKo) including group sessions (1/week) and home exercising (2/week), a placebo ultrasound group (1/week) or a control group (no treatment). HMS was measured as isometric peak torque of hip abduction, adduction, flexion, and extension. Adherence to exercise and safety aspects were monitored as additional outcomes.
RESULTS: Baseline adjusted post intervention HMS of the THüKo group were higher compared to the control group (differences of 0.11-0.27 Nm/kg, p < 0.01) and to the placebo ultrasound group (differences of 0.09-0.19 Nm/kg, p < 0.01). Adherence to exercise was high (about 90%). No subject had to refuse from training because of an exercise related adverse event and exercise related pain was only of intermittent nature without sustainable adverse effects.
CONCLUSIONS: The Tübingen exercise therapy approach has shown to have a significant positive effect on HMS. Its implementation has shown to be feasible and safe according to the percentage of exercise participation and the absence of sustainable adverse events.

More details about the exercise program can be found in this paper here.  If you have hip osteoarthritis, this may be something you can discuss with your physician.

The Genetic Architecture Of Osteoarthritis

Genetic links between higher BMI and osteoarthritis exist. Abstract:

Osteoarthritis is a common complex disease imposing a large public-health burden. Here, we performed a genome-wide association study for osteoarthritis, using data across 16.5 million variants from the UK Biobank resource. After performing replication and meta-analysis in up to 30,727 cases and 297,191 controls, we identified nine new osteoarthritis loci, in all of which the most likely causal variant was noncoding. For three loci, we detected association with biologically relevant radiographic endophenotypes, and in five signals we identified genes that were differentially expressed in degraded compared with intact articular cartilage from patients with osteoarthritis. We established causal effects on osteoarthritis for higher body mass index but not for triglyceride levels or genetic predisposition to type 2 diabetes.

Cartilage Repair, Cell Signaling, And Osteoarthritis

Cartilage repair, aging, and osteoarthritis; new findings described here.  Cell signaling pathways are involved; modulating these pathways may be part of new, optimized treatments for this disease.  

Ageing processes play a major contributing role for the development of Osteoarthritis (OA). This prototypic degenerative condition of ageing is the most common form of arthritis and is accompanied by a general decline, chronic pain and mobility deficits. The disease is primarily characterized by articular cartilage degradation, followed by subchondral bone thickening, osteophyte formation, synovial inflammation and joint degeneration. In the early stages, osteoarthritic chondrocytes undergo phenotypic changes that increase cell proliferation and cluster formation and enhance the production of matrix-remodelling enzymes. In fact, chondrocytes exhibit differentiation plasticity and undergo phenotypic changes during the healing process. Current studies are focusing on unravelling whether OA is a consequence of an abnormal wound healing response. Recent investigations suggest that alterations in different proteins, such as TGF-ß/BMPs, NF-Kß, Wnt, and Cx43, or SASP factors involved in signalling pathways in wound healing response, could be directly implicated in the initiation of OA. Several findings suggest that osteoarthritic chondrocytes remain in an immature state expressing stemness-associated cell surface markers. In fact, the efficacy of new disease-modifying OA drugs that promote chondrogenic differentiation in animal models indicates that this may be a drug-sensible state. In this review, we highlight the current knowledge regarding cellular plasticity in chondrocytes and OA. A better comprehension of the mechanisms involved in these processes may enable us to understand the molecular pathways that promote abnormal repair and cartilage degradation in OA. This understanding would be advantageous in identifying novel targets and designing therapies to promote effective cartilage repair and successful joint ageing by preventing functional limitations and disability.

Exercise Instead Of Drugs For Knee Osteoarthritis

It should come as no surprise of readers of this blog that quadriceps (muscles of the front of the thigh) exercise can as effective as nonsteroidal anti-inflammatory drugs against knee osteoarthritis.  And yet, taking pills is the “default” for the medical profession – everything “solved” with drugs.  Abstract:

OBJECTIVES:

To examine the effect of home-based exercise on knee osteoarthritis among Japanese in comparison with that of nonsteroidal antiinflammatory drugs (NSAIDs).

DESIGN:

An open-labeled, randomized, controlled, multiclinic trial compared home-based quadriceps exercise with NSAIDs. Treatments were basically evaluated after 8 wks and compared with the baseline scores. Outcomes were evaluated with a set of psychometric measurements including the Western Ontario and McMaster Universities Arthritis Index (WOMAC), 36-Item Short-Form Health Survey (SF-36), Japanese Knee Osteoarthritis Measure (JKOM), and pain with the visual analog scale.

RESULTS:

A total of 142 patients entered this trial to provide the baseline data. After 21 cases withdrew, the final number analyzed was 121 cases: 63 for the exercise group and 58 for the NSAIDs group. Between these two groups, there was no significant difference in gender, age, body height and weight, body mass index, or each score at baseline. The subjects in both groups showed improvements in all scores at the end of intervention. The difference in improvement rate of each score between the two groups was not statistically significant, though the mean rank score measured with JKOM in the exercise was slightly better than that of the NSAIDs.

CONCLUSIONS:

Home-based exercise using quadriceps strengthening improves knee osteoarthritis no less than NSAIDs.

HMGB Proteins, Wnt Signaling, And Arthritis

HMGB proteins bind DNS to affect gene expression, and are associated with arthritis.  HMGB1 has been linked to inflammation in rheumatoid arthritis, and HMGB2 is associated with age-related osteoarthritis.  Effects of HMGB2 on bone is related to Wnt signaling, which is also often deregulated in cancer. These findings may lead to novel therapies for arthritis, particularly, with respect to Wnt signaling, for osteoarthritis. Abstract: 

The high-mobility group box (HMGB) family includes four members: HMGB1, 2, 3 and 4. HMGB proteins have two functions. In the nucleus, HMGB proteins bind to DNA in a DNA structure-dependent but nucleotide sequence-independent manner to function in chromatin remodeling. Extracellularly, HMGB proteins function as alarmins, which are endogenous molecules released upon tissue damage to activate the immune system. HMGB1 acts as a late mediator of inflammation and contributes to prolonged and sustained systemic inflammation in subjects with rheumatoid arthritis. By contrast, Hmgb2 -/- mice represent a relevant model of aging-related osteoarthritis (OA), which is associated with the suppression of HMGB2 expression in cartilage. Hmgb2 mutant mice not only develop early-onset OA but also exhibit a specific phenotype in the superficial zone (SZ) of articular cartilage. Given the similar expression and activation patterns of HMGB2 and β-catenin in articular cartilage, the loss of these pathways in the SZ of articular cartilage may lead to altered gene expression, cell death and OA-like pathogenesis. Moreover, HMGB2 regulates chondrocyte hypertrophy by mediating Runt-related transcription factor 2 expression and Wnt signaling. Therefore, one possible mechanism explaining the modulation of lymphoid enhancer binding factor 1 (LEF1)-dependent transactivation by HMGB2 is that a differential interaction between HMGB2 and nuclear factors affects the transcription of genes containing LEF1-responsive elements. The multiple functions of HMGB proteins reveal the complex roles of these proteins as innate and endogenous regulators of inflammation in joints and their cooperative roles in cartilage hypertrophy as well as in the maintenance of joint tissue.

Wnt Signaling In Arthritis

http://www.mayoclinic.org/diseases-conditions/arthritis/home/ovc-20168903

A review on the role of Wnt signaling - often deregulated  in cancer particularly colon cancer - in arthritis can be found here. This is an example of the benefits of basic science research: first, by understanding Wnt signaling in general we better understand the diseases that exhibit aberrant forms of this signaling; second, by dissecting the finer details of how this signaling is controlled and what the downstream effects are, therapeutic interventions can be developed that targets this signaling to treat disease. Perhaps even preventive approaches can be devised as well. Arthritis may be another example of this pathway from lab bench to clinic. Abstract:

PURPOSE OF REVIEW:Arthritis defines a large group of diseases primarily affecting the joint. It is the leading cause of pain and disability in adults. Osteoarthritis (OA) affecting the knee or hip is the most common form among over 100 types of arthritis. Other types of arthritis include erosive hand OA, temporomandibular joint (TMJ) OA, facet joint OA, diffuse idiopathic skeletal hyperostosis (DISH), and spondyloarthritis (SpA). However, the specific molecular signals involved in the development and progression of OA and related forms of arthritis remain largely unknown. The canonical wingless/integrated (Wnt)/β-catenin signaling pathway could play a unique role in the pathogenesis of arthritis. In this review article, we will focus on the molecular mechanisms of Wnt/β-catenin signaling in the pathogenesis of OA and other types of arthritis.RECENT FINDINGS:Emerging evidence demonstrates that Wnts and Wnt-related molecules are involved in arthritis development and progression in human genetic studies and in vitro studies. Also, mouse models have been generated to determine the role of Wnt/β-catenin signaling in the pathogenesis of arthritis. Wnt/β-catenin signaling represents a unique signaling pathway regulating arthritis development and progression, and the molecules in this particular pathway may serve as targets for the therapeutic intervention of arthritis. Mediators and downstream effectors of Wnt/β-catenin signaling are increased in OA as well other forms of arthritis, including DISH and SpA. Through extensive investigations, including pre-clinical studies in transgenic mice and translational and human studies, the Wnt/β-catenin signaling pathway has been proven to play roles in bone and joint pathology by directly affecting bone, cartilage, and synovial tissue; further, these pathologies can be reduced through targeting this pathway. Continued investigation into the distinct molecular signaling of the Wnt/β-catenin pathway will provide additional insights toward the therapeutic intervention in arthritis.