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Glenoid morphology and rotator cuff muscle quality are important anatomic factors that can impact longevity of the glenoid component following total shoulder arthroplasty (TSA). We hypothesized that rotator cuff muscle fatty infiltration is associated with increased pathologic glenoid bone loss in glenohumeral osteoarthritis (OA).We retrospectively reviewed 190 preoperative computed tomography (CT) scans of 175 patients (mean age, 66 years; range, 44 to 90 years) who underwent TSA for the treatment of primary glenohumeral OA. Two-dimensional orthogonal CT images were reformatted in the plane of the scapula from 3-dimensional images. Pathologic joint-line medialization was defined with use of the glenoid vault model. Pathologic glenoid version was measured directly. Glenoid morphology was graded according to a modified Walch classification (subtypes A1, A2, B1, B2, B3, C1, and C2). Rotator cuff muscle fatty infiltration was assessed and assigned a Goutallier score on the sagittal CT slice just medial to the spinoglenoid notch for each muscle.There was a significant difference in the Goutallier score for the supraspinatus, infraspinatus, and teres minor muscles between Walch subtypes (p ≤ 0.05). High-grade posterior rotator cuff muscle fatty infiltration was present in 55% (21) of 38 B3 glenoids compared with 8% (3) of 39 A1 glenoids. Increasing joint-line medialization was associated with increasing fatty infiltration of all rotator cuff muscles (p ≤ 0.05). Higher fatty infiltration of the infraspinatus, teres minor, and combined posterior rotator cuff muscles was associated with increasing glenoid retroversion (p ≤ 0.05). After controlling for joint-line medialization and retroversion, B3 glenoids were more likely to have fatty infiltration of the supraspinatus and infraspinatus muscles than B2 glenoids were.High-grade rotator cuff muscle fatty infiltration is associated with B3 glenoids, increased pathologic glenoid retroversion, and increased joint-line medialization. Additional studies are needed to determine the causal relationship between these muscle changes and glenoid wear, whether these muscle changes independently affect clinical and radiographic outcomes in anatomic TSA, and whether fatty infiltration can improve postoperatively with correction of pathologic version and/or joint-line restoration.This study investigates the association between different patterns of glenoid bone loss and rotator cuff muscle fatty infiltration. Both factors have been shown to affect clinical outcome following TSA.