Glyn-Jones et al. Osteoarthritis Lancet 2015;386:376-387
- The epidemiology of the disorder is complex and multifactorial,with genetic, biological, and biomechanical components.
- Functional outcomes (of joint replacement) can be poor and the lifespan of prosthesis is limited. Consequently, the focus is shifting to disease prevention and the treatment of early osteoarthritis.
- Epidemiology
- joint biomechanics anatomical/functional
- Anatomical joint morphology
- Functional poor quadriceps function
- Systemic factors
- Estrogen due to female dominance
- Knee injury, obesity
- Genetic
- cartilage
- type II colloagen cartilege oligomeric matrix protein
- collagenases (MMP 1,3,13) and aggrecan-degrading enzymes( ADAMTS 4 and 5), seems to have important pathogenesis effects
- innate immune system
- subchondral bone
- subchondral bone is highly innervated and probably contributes to the generation of pain in disease
- Synovium
- prolifferation of synoviocytes and tissue hypertrophy is notable in established osteoarthritis.
- synoviocytes synthesis lubricants such as hyaluronic acid and lubricin.
- synoviocytesm, like chondrocytes and osteoblasts also release inflammatory mediators and degradative enzymes
- synovitis predicts the development and progression of symptoms
- Systemic inflammation
- adipokines
- Diagnosis
- The greatest limitation of addressing structural osteoarthritis is our inability to predict whether it will progress to clinical osteoarthritis.
- To the poor relation between symptoms and structure, clinical benefit from treatment of structural osteoarthritis is not guaranteed. Therefore, studies trying to target the earliest osteoarthritis by modifying structural disease must also take symptoms into account.
- Imaging
- Joint space width is the only structural endpoint accepted by the European medicines agency and the USS food and drug administration to prove effectiveness of disease-modifying osteoarthritis drugs, yet it has many limitations. It lacks sensitivity and cannot detect localized cartilage damage.
- MRI is more sensitive in detecting early structural changes.
- Physiological MRI permits detection of the very first changes that occur during osteoarthritis development by assessing the biochemical composition of tissues.
- protocol used to assay glycosaminoglycan content include delayed gadlinium-ennhanced MRI of cartilege, chemical exchange saturation transfer, sodium scanning
- dGMRIC, CEST
- Both effector molecules, such as cytokines and enzymes, and extracellular matrix constituents, such as precursors or degradation products of collagen and proteoglycan, have potential as biochemical markers.
- CTX-II (C-terminal telopeptie of collagen type II) urine, cartilege oligomeric matrix protein (serum)
- sensitivity and specificity are poor for all biochemical markers and worse than those of imaging measures.
- The combination of CTX-II with MRI measurements has the greatest prognostic value for progression of structural knee osteoarthritis 9OR 5.8)
