Plain radiography as an outcome measure in clinical trials involving patients with knee osteoarthritis

The identification of pharmacologic agents that inhibit matrix metalloproteinase activity and may serve as effective disease-modifying osteoarthritis drugs (DMOADs) in humans has led to interest in the ability of plain radiographic methods to detect early cartilage damage and assess progressive cartilage changes of knee osteoarthritis (OA). Conventional knee radiography lacks sufficient standardization of key elements of the radioanatomic positioning of the knee to avoid significant, probably insurmountable, error variation in the measurement of tibiofemoral joint space width (JSW), the surrogate for the thickness of articular cartilage in radiographic images. Recently, several protocols for the use of fluoroscopy to standardize the radioanatomic position of the knee in a plain radiograph have been shown to afford notably more precise measurement of medial tibiofemoral JSW than can be derived from unstandardized, conventional techniques. A field test of one of these protocols suggests that DMOAD trials with respect to sample size or duration of treatment necessary to detect true OA progression and demonstrate a drug effect may be more feasible.