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This study examined if costamere turnover is affected by a rotator cuff tear in a previously established ovine model. We found the activity of focal adhesion kinase (FAK), a main regulator of costamere turnover, was unchanged at 2 weeks but decreased by 27% 16 weeks after surgical release of the <jats:italic>infraspinatus<\/jats:italic> tendon. This was accompanied by cleavage of the costamere protein talin into a 190\u2009kDa fragment while full length talin remained unchanged. At 2 weeks after tendon release, muscle volume decreased by 17\u2009cm<jats:sup>3<\/jats:sup> from an initial 185\u2009cm<jats:sup>3<\/jats:sup>, the fatty tissue volume was halved, and the contractile tissue volume remained unchanged. After 16 weeks, the muscle volume decreased by 36\u2009cm<jats:sup>3<\/jats:sup>, contractile tissue was quantitatively lost, and the fat content increased by 184%. Nandrolone administration mitigated the loss of contractile tissue by 26% and prevented fat accumulation, alterations in FAK activity, and talin cleavage. Taken together, these findings imply that muscle remodeling after tendon release occurs in two stages. The early decrease of muscle volume is associated with reduction of fat; while, the second stage is characterized by substantial loss of contractile tissue accompanied by massive fat accumulation. Regulation of costamere turnover is associated with the loss of contractile tissue and seems to be impacted by nandrolone treatment. Clinically, the costamere may represent a potential intervention target to mitigate muscle loss after a rotator cuff tear. \u00a9 2017 The Authors. <jats:italic>Journal of Orthopaedic Research<\/jats:italic>\u00ae published by Wiley Periodicals, Inc. on behalf of the Orthopaedic Research Society. 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