Osteoarthritis - L12 Flashcards
What are the advantages of exercise for osteoarthritis?
- Pain relieve
- Improved performance of activities
What are possible reasons why physical exercisy therapy for knee osteoarthritis is beneficial for pain, physical function, and QoL, but where the effects are moderate?
- Heterogeneous population with different underlying mechanisms for the development of osteoarthritis.
- Progression of osteoarthritis.
- Variability in exercise dose.
Name factors that are associated with increasing muscle weakness in osteoarthritis.
- Avoidance of activities due to pain
- Low-grade inflammation
A key process in osteoarthritis is local and systemic inflammation. Explain how local and systemic inflammation is seen in patients with osteoarthritis.
- Local inflammation: synovial inflammation foundin 40-50% of knee osteoarthritis patients.
- Systemic inflammation: slight-moderate increases in CRP and ESR and elevated levels of circulatory cytokines (e.g. IL-6, TNF-a) and adipokines (e.g. leptin).
Explain the role of inflammation in osteoarthritis.
- Inflamed synovium results in the production of pro-inflammatory mediators.
- Pro-inflammatory mediators have their effect on angiogenesis, immune cells and chondrocytes.
- Chondrocytes are stimulated to produce pro-inflammatory mediators and MMPs that result in tissue damage.
- The synovium becomes more inflamed due to tissue damage, which initiates a vicious cycle.
Osteoarthritis can be a result of joint instability and abnormal loading. Explain what the consequence is of this and how this leads to osteoarthritis.
- Joint instability and abnormal loading
- Integrin-cytoskeleton and ion-stretch mechanoreceptors stimulate catabolic pathway.
- MMPs are produced which lead to the breakdown of cartilage ECM.
- The breakdown of ECM initiates a vicious cycle where ECM breakdown products are sensed by specific chondrocyte receptors, where catabolic pathways are stimulated again.
- Ultimately, this leads to articular cartilage degradation and osteoarthritis.
What evidence is there that suggests that exercise influences inflammation in osteoarthritis?
- Evidence on the effect of exercise on knee osteoarthritis suggests that exercise has an anti-inflammatory effect.
- Decreases in markers of inflammation (CRP, TNF-a, leptin, IL-6) after 12 weeks of resistance training.
- Physical inactivity leads to accumulation of visceral fat, which might further enhance the development of chronic diseases in a vicious cycle of chronic inflammation
- Myokines produced by skeletal muscle in response to exercise, might mediate either direct anti-inflammatory responses or improve comorbidities.
What is the difference between a rheumatoid arthritis joint and a osteoarthritis joint?
- Rheumatoid arthritis joint: bone and cartilage destruction, presence of B cells, macrophages, cytokines, and T cells.
- Osteoarthritis joint: multifactorial degenerative joint disease affecting many tissues in the joint such as: collateral ligament, articular cartilage, meniscus. Additionally, slight to moderate systemic elevation of CRP and ESR and elevated levels of circulating cytokines.
The underlying idea of the slide was to highlight that these diseases fall under the category rheumatic and musculoskeletal disease (RMD) and that they have inflammation as a common factor.
What is commonly reported in patients with RMD?
Decreased muscle mass, weakness and fatigue, leading to a decreased QoL.
What is the difference between atrophy and intrinsic muscle dysfunctioning?
- Atrophy: loss of muscle mass
- Intrinsic muscle dysfunction: decreased muscle function due to intra-muscular dysfunction in force production.
What is excitation-contraction coupling (ECC)?
The events leading to the contraction of skeletal muscle fibers.
So intrinsic muscle dysfunction can be due to problems in excitation-contraction coupling (ECC). What could be causes of problems in ECC?
- Reduced SR Ca2+ release
- Decreased myofibrillar Ca2+ sensitivity
- Impaired ability of cross-bridges to generate muscle force
These dysfunctioning process could be due to oxidative stress, impaired glucose metabolism and mitochondrial dysfunctioning.
How can oxidative stress impair muscle functioning?
Oxidative stress can cause post-translational modifications causing decreased muscle force.
PET imaging could be used to study intra-muscular differences in the whole body. Why is PET imaging not yet used to its full extend regarding DRM diseases?
Because there is not much known about muscle PET imaging and there are no comparative studies between RMDs.
