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Ultra-endurance sports are associated with prolonged physical exercise both during training and competition. Musculoskeletal injuries are common as a result of the repetitive physical stresses. Stress fractures in the weight-bearing bones should always be suspected when ultra-endurance athletes present with pain over bony structures. Most stress fractures can be treated with activity modifications but some such as femoral neck and tibial shaft stress fractures may require operative fixation. The knee seems to be the most frequent source of injuries in ultra-endurance athletes. Patellofemoral symptoms from tendon injuries or chondral problems are common injuries and can be challenging to treat. Lower leg, ankle, and foot injuries also make up a significant portion of the ultra-endurance injuries. Peritendinitis of the extensor tendons at the extensor retinaculum of the anterior ankle or “ultramarathoner’s ankle” seems to be a unique injury associated with ultramarathons. Other lower leg injuries include medial tibial stress syndrome (MTSS) and chronic exercise-induced compartment syndrome (CECS).