Fig.1.

Theoretical natural history of symptomatic OA progression. The impact of intermittent discrete (potentially benign) flare-up episodes (red bars) progress in frequency, intensity (height of bars) and duration (width of bars), with reducing periods of remission and capacity for complete symptom resolution. These acute symptom events drive the underlying disease process, eventually resulting in constant pain, complete loss of organ reserve (capacity to restore homeostasis) and synovial joint failure. Each red bar representing a flare-up is preceded by potential exposure flare-up triggers. The black vertical dashed line represents a period of time after which flare-ups may no longer be potentially benign. The black dotted line represents the course of pain over time. The blue dotted line represents the organ reserve over time, which theoretically may diminish with repeated and/or frequent flare-ups.