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A comprehensive review covers current understanding of the mechanisms of osteoarthritis, including histology and signaling pathways, and options for early intervention and prevention of progression.
Glyn-Jones S, Palmer AJR, Agricola R, et al. Seminar: OsteoarthritisLancet, Online: 2015; doi: 10.1016/S0140-6736(14)60802-3
This review covers current understanding of the mechanisms of osteoarthritis (OA), including histology and signaling pathways, and options for early intervention and prevention of progression.
Tissues are eroded by mechanical stress, but respond to erosion and mechanical stress itself by producing cytokines, so OA can be alleviated by addressing both mechanical and chemical targets.
Figure 3 summarizes the signaling pathways and structural changes in the development of OA.
• In the cartilage, chondrocytes produce inflammatory response proteins and metalloproteinases. The authors see OA as a loss of regenerative capacity (which declines with age), so matrix remodeling proteins might be stimulated to restore that regenerative capacity.
• In the subchondral bone, new MRI imaging can visualize vascular penetration, formation of osteophytes and subchondral cysts.
• Synoviocytes also release inflammatory mediators and degradative enzymes after the initial insult, and synovitis is a target for intervention.
OA is diagnosed by symptoms, but by the time the patient has symptoms, the damage is advanced and probably irreversible. The authors define structural OA as cartilage loss without inflammatory or crystal arthropathy, even without symptoms.
Structural OA can be assayed by newly available biomarkers. The authors also favor MRI for measuringearly changes. Physiological MRI can assess biochemical composition of tissues. Other MRI protocols are responsive to cartilage orientation and water content. Bone marrow, meniscal status, and synovitis on MRI can further predict disease progression.
Since much of OA is caused by misalignment of bones, the authors review surgical corrections, along with grafting, which are widely adopted although hard evidence is limited.
• Significantly, periarticular osteotomy and joint distraction are supported by evidence of cartilage regeneration.
• Microfracture of subchondral bone, and cell-based therapies such as autologous chondrocyte implantation, have weaker results but are promising.
• Glucosamine, chondroitin, hyaluronic acid, doxycycline, and FGF-18 all show the difficulty of demonstrating meaningful benefits.
Weight loss and exercise head the list of interventions, as always. With markers to indicate subclinical OA before the symptoms start, this effective treatment could be started early enough to prevent or reduce further damage.
It is still puzzling why obesity should be a risk factor for OA even in non-weight-bearing joints, such as those in the hand.