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Muscles of the rotator cuff undergo retraction, atrophy, and fatty infiltration after a chronic tear, and a rabbit model has been used to investigate these changes. The purpose of this study was to test the hypothesis that the administration of anabolic steroids can diminish these muscular changes following experimental supraspinatus tendon release in the rabbit.The supraspinatus tendon was released in twenty New Zealand White rabbits. Musculotendinous retraction was monitored over a period of six weeks. The seven animals in group I had no additional intervention, the six animals in group II had local and systemic administration of nandrolone decanoate, and the seven animals in group III had systemic administration of nandrolone decanoate during the six weeks. Two animals (group III) developed a postoperative infection and were excluded from the analysis. At the time that the animals were killed, in vivo muscle performance as well as imaging and histological muscle changes were investigated.The mean supraspinatus retraction was higher in group I (1.8 cm; 95% confidence interval: 1.64, 2.02 cm) than in group II (1.5 cm; 95% confidence interval: 1.29, 1.81 cm) or III (1.2 cm; 95% confidence interval: 0.86, 1.54 cm). Histologically, no fatty infiltration was measured in either treated group II (mean, 2.2%; range, 0% to 8%) or III (mean, 1%; range, 0% to 3.4%), but it was measured in the untreated group I (mean, 5.9%; range, 0% to 14.1%; p = 0.031). The radiographic cross-sectional area indicating atrophy and the work of the respective muscle during one standardized contraction with supramaximal stimulation decreased in all groups, but the work of the muscle was ultimately highest in group III.To our knowledge, this is the first documentation of partial prevention of important muscle alterations after retraction of the supraspinatus musculotendinous unit caused by tendon disruption. Nandrolone decanoate administration in the phase after tendon release prevented fatty infiltration of the supraspinatus muscle and reduced functional muscle impairment caused by myotendinous retraction in this rabbit rotator cuff model, but two of seven rabbits that received the drug developed infections.This study provides a novel approach that may have potential to diminish the irreparable structural and functional changes of the musculotendinous unit associated with chronic rotator cuff tear, but complications of anabolic steroid use also need to be considered.