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Background: Muscle volume is important in shoulder function. It can be used to estimate shoulder muscle balance in health, pathology, and repair and is indicative of strength based on muscle size. Although prior studies have shown that muscle area on two-dimensional (2-D) images correlates with three-dimensional (3-D) muscle volume, they have not provided equations to predict muscle volume from imaging nor validation of the measurements.Questions/purposes: We wished to create an algorithm that quickly, accurately, and reliably estimates the volume of the shoulder muscles using cross-sectional area on MR images with low error. Specifically, we wished to (1) determine which MR imaging planes provide the highest correlation between shoulder muscle cross-sectional area and volume; (2) derive equations to predict muscle volume from cross-sectional area and validate their predictive capability; and (3) quantify the reliability of muscle cross-sectional area measurement.Methods: Three-dimensional MRI was performed on 10 cadaver shoulders, with sample size chosen for comparison to prior studies of shoulder muscle volume and in consideration of the cost of comprehensive analysis, followed by dissection for muscle volume measurement via water displacement. From each MR series, 3-D models of the rotator cuff and deltoid muscles were generated, and 2-D slices of these muscle models were selected at defined anatomic landmarks. Linear regression equations were generated to predict muscle volume at the plane(s) with the highest correlation between volume and area and for planes identified in prior studies of muscle volume and area. Volume predictions from MR scans of six different cadaver shoulders were also made, after which they were dissected to quantify muscle volume. This validation population allowed the calculation of the predictive error compared with actual muscle volume. Finally, reliability of measuring muscle areas on MR images was calculated using intraclass correlation coefficients for inter-rater reliability, as measured between two observers at a single time point.Results: The rotator cuff planes with the highest correlation between volume and area were the sum of the glenoid face and the midpoint of the scapula, and for the deltoid, it was the transverse plane at the top of the greater tuberosity. Water and digital muscle volumes were highly correlated (r ≥ 0.993, error < 4%), and muscle areas correlated highly with volumes (r ≥ 0.992, error < 2%). All correlations had p < 0.001. Muscle volume was predicted with low mean error (< 10%). All intraclass correlation coefficients were > 0.925, suggesting high inter-rater reliability in determining muscle areas from MR images.Conclusion: Deltoid and rotator cuff muscle cross-sectional areas can be reliably measured on MRI and predict muscle volumes with low error.Clinical Relevance: Using simple linear equations, 2-D muscle area measurements from common clinical image analysis software can be used to estimate 3-D muscle volumes from MR image data. Future studies should determine if these muscle volume estimations can be used in the evaluation of patient function, changes in shoulder health, and in populations with muscle atrophy. Additionally, these muscle volume estimation techniques can be used as inputs to musculoskeletal models examining kinetics and kinematics of humans that rely on subject-specific muscle architecture. [ABSTRACT FROM AUTHOR]

Background: Although glenoid morphology has been associated with fatty infiltration of the rotator cuff in arthritic shoulders, the association of rotator cuff muscle area with specific patterns of glenoid wear has not been studied. The purpose of our study was to assess the associations of glenoid deformity in primary glenohumeral osteoarthritis and rotator cuff muscle area.Methods: A retrospective study of 370 computed tomographic (CT) scans of osteoarthritic shoulders was performed. Glenoid deformity according to the modified Walch classification was determined, and retroversion, inclination, and humeral-head subluxation were calculated using automated 3-dimensional software. Rotator cuff muscle area was measured on sagittal CT scan reconstructions. A ratio of the area of the posterior rotator cuff muscles to the subscapularis was calculated to approximate axial plane potential force imbalance. Univariate and multivariate analyses to determine associations with glenoid bone deformity and rotator cuff measurements were performed.Results: Patient age and sex were significantly related to cuff muscle area across glenoid types. Multivariate analysis did not find significant differences in individual rotator cuff cross-sectional areas across glenoid types, with the exception of a larger supraspinatus area in Type-B2 glenoids compared with Type-A glenoids (odds ratio [OR], 1.5; p = 0.04). An increased ratio of the posterior cuff area to the subscapularis area was associated with increased odds of a Type-B2 deformity (OR, 1.3; p = 0.002). Similarly, an increase in this ratio was significantly associated with increased glenoid retroversion (beta = 0.92; p = 0.01) and humeral-head subluxation (beta = 1.48; p = 0.001). Within the Type-B glenoids, only posterior humeral subluxation was related to the ratio of the posterior cuff to the subscapularis (beta = 1.15; p = 0.001).Conclusions: Age and sex are significantly associated with cuff muscle area in arthritic shoulders. Asymmetric glenoid wear and humeral-head subluxation in osteoarthritis are associated with asymmetric atrophy within the rotator cuff transverse plane. Increased posterior rotator cuff muscle area compared with anterior rotator cuff muscle area is associated with greater posterior glenoid wear and subluxation. It is unclear if the results are causative or associative; further research is required to clarify the relationship.Level Of Evidence: Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence. [ABSTRACT FROM AUTHOR]

Background: Humeral bone loss is commonly encountered during revision shoulder arthroplasty and anticipating humeral bone defects can help the revision surgeon make appropriate plans to achieve adequate fixation and stability. No validated classification system exists to characterize humeral bone loss in the setting of revision shoulder arthroplasty.Questions/purposes: The purposes of this study were (1) to create a classification system for humeral bone loss in revision shoulder arthroplasty; (2) to determine the classification system's reliability; and (3) to determine whether humeral bone loss type is associated with intraoperative humeral-related reconstruction characteristics.Methods: This was a comparative retrospective radiographic study. First, six surgeons from five centers collaborated to create a classification by consensus. Second, two surgeons from two other centers who had fellowship training in shoulder and elbow surgery, who were blinded to each other's grades and all patient details other than plain radiographs, and who were not involved in creation of the system, classified true AP, AP, and lateral (axillary and/or scapular-Y) radiographs from 108 revision (413 radiographs) from one center that were performed between November 15, 2006, and January 4, 2018. Interobserver reliability was calculated by comparing those two reviews and determining Cohen's κ. In addition, one reviewer repeated his assessments twice, 4 months apart, to determine intraobserver reliability using Cohen's κ. Third, we performed a retrospective chart study of these same revisions to determine intraoperative humeral-related reconstruction characteristics such as the use of greater tuberosity fixation, stem length, humeral bone grafting, and the use of proximal humeral replacement or total humeral replacement; at the center where these revisions were performed during that timespan, no attempt to classify bone loss was made. During that period, the general indications for greater tuberosity fixation included the absence of a stable osseous connection between the greater tuberosity and the shaft of the humerus with a tuberosity amendable to repair; the general indications for use of longer stems were inability to obtain a minimum of two cortical widths of overlap between the implant and the humeral diaphysis and/or loss of the greater tuberosity; and the general indications for proximal and total humeral replacement were bone loss that was felt to be too severe to allow reconstruction with allograft.Results: The classification system consists of three types of humeral bone loss: Type 1 is loss of the epiphysis with subtypes for loss of the calcar and loss of the greater tuberosity; Type 2 is loss of the metadiaphysis above the deltoid attachment with a subtype for cortical thinning; and Type 3 is bone loss extending below the deltoid attachment with a subtype for cortical thinning. We studied 108 revisions: 38 (35%) without bone loss, 34 (31%) Type 1, 27 (25%) Type 2, and nine (8%) Type 3. For reliability, interrater κ was 0.545 and in 71% (77 of 108) of revisions, the two raters agreed on a numeric type. Intrarater κ was 0.615 and in 77% (83 of 108) of revisions, the rater agreed with himself as to the numeric type. Stem length increased with class type (Type 1 median [range] 130 [70-210], Type 2 150 [70-210], Type 3 190 [70-240], p = 0.005). Most greater tuberosity fixation for intraoperative fracture was in Types 1 and 2 (13 of 18 compared with the five of 18 of greater tuberosity fixation that was within Types 0 and 3, p = 0.043). Most bone grafting was in Types 2 and 3 (eight of 13 compared with five of 13 of bone grafting was in Types 0 and 1, p = 0.044). Most proximal humeral and total humeral replacements were in Type 3 (three of four compared with one of four, p < 0.001).Conclusions: We developed the Proximal Humeral Arthroplasty Revision Osseous inSufficiency (PHAROS) system, which has adequate, if imperfect, reliability to classify humeral bone loss in the setting of revision shoulder arthroplasty. This classification system may be useful to anticipate the complexity of humeral reconstruction. Further validation incorporating advanced imaging and further evaluators will be necessary.Level Of Evidence: Level III, diagnostic study. [ABSTRACT FROM AUTHOR]

Age affects gross shoulder range of motion (ROM), but biomechanical changes over a lifetime are typically only characterized for the humerothoracic joint. Suitable age-related baselines for the scapulothoracic and glenohumeral contributions to humerothoracic motion are needed to advance understanding of shoulder injuries and pathology. Notably, biomechanical comparisons between younger or older populations may obscure detected differences in underlying shoulder motion. Herein, biplane fluoroscopy and skin-marker motion analysis quantified humerothoracic, scapulothoracic, and glenohumeral motion during 3 static poses (resting neutral, internal rotation to L4-L5, and internal rotation to maximum reach) and 2 dynamic activities (scapular plane abduction and external rotation in adduction). Orientations during static poses and rotations during active ROM were compared between subjects <35 years and >45 years of age (N = 10 subjects per group). Numerous age-related kinematic differences were measured, ranging 5–22°, where variations in scapular orientation and motion were consistently observed. These disparities are on par with or exceed mean clinically important differences and standard error of measurement of clinical ROM, which indicates that high resolution techniques and appropriately matched controls are required to avoid confounding results of studies that investigate shoulder kinematics. Understanding these dissimilarities will help clinicians manage expectations and treatment protocols where indications and prevalence between age groups tend to differ. Where possible, it is advised to select age-matched control cohorts when studying the kinematics of shoulder injury, pathology, or surgical/physical therapy interventions to ensure clinically important differences are not overlooked. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to determine whether the addition of hydrogen peroxide to the preoperative skin preparation for primary total shoulder arthroplasty is associated with a difference in patient-reported outcomes, risk for postoperative infection, and risk for revision surgery at a minimum of 2-year follow-up., Methods: This was a prospective, blinded, and controlled trial, which included a consecutive series of patients undergoing primary shoulder arthroplasty. The control group underwent standard sterile skin preparation using ethyl alcohol and ChloraPrep applicators, and the peroxide group had the same preparation with the addition of hydrogen peroxide between the alcohol and ChloraPrep applications. We then compared patient-reported outcome scores (American Shoulder and Elbow Surgeons Shoulder Score [ASES], simple shoulder test [SST], visual analog scale [VAS]), infections, and revision surgeries between the two groups at 2-year follow-up., Results: Of the 61 patients included in the original study, 52 of 58 (85%) living patients agreed to participate in this study. No preoperative differences were observed between groups. No difference was observed in ASES, SST, or VAS scores at 2 years. More revision surgeries were done in the control group (7 versus 2, P = 0.268) and Cutibacterium acnes infections (2 versus 0, P = 0.168)., Conclusion: The addition of hydrogen peroxide to the preoperative skin preparation before primary shoulder arthroplasty is safe, and additional research is warranted to investigate whether it may decrease the risk for revision surgery and postoperative C acnes infection., Level of Evidence: III., (Copyright © 2024 by the American Academy of Orthopaedic Surgeons.)

Background: Over-prescription of opioids in the United States increases risks of opioid dependence, overdose, and death. Increased perioperative and postoperative opioid use during orthopedic shoulder surgery is a significant risk factor for long term opioid dependence. The authors hypothesized that a multidisciplinary perioperative pain management program (Transitional Pain Service or TPS) for major shoulder surgery would lead to a reduced amount of opioids required postoperatively., Methods: A TPS was implemented at a Veterans Affairs Medical Center focused on non-opioid pain management and cessation support. Opioid consumption during the implementation of the TPS was compared to a historical cohort. All patients undergoing shoulder arthroplasty or rotator cuff repair were included. The primary outcome was the proportion of patients continuing opioid use at 90 days postoperatively. Secondary outcomes included postoperative pain scores, time to opioid cessation, and median opioid tablets consumed at 90-days. A multivariable model was developed to predict total opioid use at 90-days postoperatively. Kaplan Meier curves were calculated for time to opioid cessation., Results: The TPS group demonstrated decreased persistent opioid use at 90 days post-discharge (12.6% vs. 28.6%; p=0.018). Independent predictors associated with increased total opioid tablet prescriptions at 90 days included length of stay (β=19.17), anxiety diagnosis (β=37.627), and number of tablets prescribed at discharge (β=1.353). Shoulder arthroplasty surgery (TSA) was associated with decreased 90-day opioid utilization (β= -32.535) when compared to cuff repair (RCR). Median time to cessation was shorter in TSA (6 days) when compared with RCR (8 days). Pain scores were reduced compared to population mean by post-discharge day 2 for TSA and by post-discharge day 7 for RCR. Median number of post-discharge opioid tablets (oxycodone 5 mg) consumed under TPS management was 25 in both RCR and TSA surgery groups (180 MME)., Discussion and Conclusions: This study demonstrates that a TPS reduces the amount of opioid use of patients undergoing shoulder arthroplasty or cuff repair at 90 days when compared with a historical control. Multivariable regression indicated that fewer opioid tablets at discharge was a modifiable factor that may aid in reducing opioid consumption and that anxiety diagnosis, increased length of stay, and cuff repair surgery were other factors independently associated with increased opioid consumption. This data will assist surgeons in counseling patients, setting narcotic use expectations, and minimizing overprescribing. Use of a similar multidisciplinary perioperative pain management program may greatly reduce opioid over prescriptions nationally., (Copyright © 2024. Published by Elsevier Inc.)

Background: One method to augment rotator cuff repair is to pass dermal allograft pledgets along the sutures that bridge from the medial to the lateral row. It remains unclear whether this augmentation method alters repair biomechanics., Methods: This was a controlled laboratory study. After an a priori power analysis, 9 pairs of rotator cuffs underwent double-row suture bridge rotator cuff repair, half randomized to augmentation with dermal allograft pledgets passed along the suture bridge sutures. Repairs were then mounted on a material testing system and loaded cyclically 500 cycles to measure applied force and displacement. Repairs then underwent ultimate failure testing, and stiffness, ultimate failure force, and ultimate failure displacement were measured. Paired t tests were performed to compare between groups., Results: There were no differences between groups in construct gapping with cyclic loading after 500 cycles (P = .885). There were no differences between the augmented and control groups in yield force (103.5 ± 5.0 vs. 101.4 ± 5.9 N, respectively, P = .183), stiffness (94.2 ± 13.9 vs. 90.9 ± 13.8, P = .585), or ultimate failure force (255.3 ± 65.8 vs. 285.3 ± 83.2, P = .315). There were no differences between groups in failure modes, with most specimens failing by cuff tissue tearing within or medial to the construct., Conclusion: The addition of dermal allograft pledgets does not positively or negatively influence the time-zero biomechanical characteristics of double-row suture bridge rotator cuff repair., (Copyright © 2024. Published by Elsevier Inc.)

Background: Both inlay and onlay humeral implants are available for reverse total shoulder arthroplasty (rTSA), but biomechanical data comparing these components remain limited. This study investigated the effects of inlay and onlay rTSA humeral components on shoulder biomechanics using a biorobotic shoulder simulator., Methods: Twenty fresh-frozen cadaveric shoulders were tested before and after rTSA with either an inlay or onlay humeral implant. Comparisons were performed between the most commonly implanted configurations for each implant (baseline) and with a modification to provide equivalent neck-shaft angles (NSAs) for the inlay and onlay configurations. Specimens underwent passive range-of-motion (ROM) assessment with the scapula held static, and scapular-plane abduction was performed, driven by previously collected human-subject scapulothoracic and glenohumeral kinematics. Passive ROM glenohumeral joint angles were compared using t tests, whereas muscle force and excursion data during scapular-plane elevation were evaluated with statistical parametric mapping and t tests., Results: Maximum passive elevation was reduced for the inlay vs. onlay humeral components, although both implants caused reduced passive elevation vs. the native joint. Inlay rTSA also demonstrated reduced passive internal rotation at rest and increased external rotation at 90° of humerothoracic elevation vs. the native joint. All preoperative planning estimates of ROM differed from experiments. Rotator cuff forces were elevated with an onlay vs. inlay humeral implant, but simulated muscle excursions did not differ between systems. Compared with the native joint, rotator cuff forces were increased for both inlay and onlay implants and deltoid forces were reduced for inlay implants. Muscle excursions were dramatically altered by rTSA vs. the native joint. Comparisons of inlay and onlay humeral implants with equivalent NSAs were consistent with the baseline comparisons., Conclusions: Rotator cuff forces required to perform scapular-plane abduction increase following rTSA using both inlay and onlay implants. Rotator cuff forces are lower with inlay implants compared with onlay implants, although inlay implants also result in reduced passive-elevation ROM. Deltoid forces are lower with inlay implants in comparison to the native joint but not with onlay implants. The differences between inlay and onlay components are largely unaffected by NSA, indicating that these differences are inherent to the inlay and onlay designs. In those patients with an intact rotator cuff, decreased rotator cuff forces to perform abduction with an inlay humeral implant compared with an onlay implant may promote improved long-term outcomes owing to reduced deltoid muscle fatigue when using an inlay implant., (Copyright © 2023 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.)

Background: Preoperative planning is an integral aspect of managing complex deformity in reverse shoulder arthroplasty (RSA). The purpose of this study was to compare the success of patient-specific instrumentation (PSI) and 3D computer-assisted planning with standard instrumentation (non-PSI) in achieving planned corrections of the glenoid among patients undergoing RSA with severe bony deformity requiring glenoid bone grafts., Methods: A retrospective case-control study was performed, including all patients that underwent RSA with combined bone grafting procedures (BIO-RSA or structural bone grafting) for severe glenoid deformity by a single study between June 2016 and July 2023. Patients were required to have preoperative and postoperative CT scans as well as preoperative 3D planning performed for inclusion. Patients were divided into two groups based on the use of 3D computer-assisted planning with or without PSI (PSI vs. non-PSI). The corrected inclination and version were measured by two separate reviewers on preoperative and postoperative 2D CT scans and compared to their corresponding preoperative planning goals utilizing bivariate analyses., Results: We identified 45 patients that met our inclusion criteria (22 PSI and 23 non-PSI). Preoperative inclination (mean ± SD) (PSI 10.12° ± 15.86°, non-PSI 9.43° ± 10.64°; P = .864) and version (PSI -18.78° ± 18.3°, non-PSI -17.82° ± 11.49°; P = .835) measurements were similar between groups. No significant differences in the mean deviation (error) between the postoperative and planned inclination (PSI 5.49° ± 3.72; non-PSI 6.91° ± 5.05; P = .437) and version (PSI 8.37° ± 5.7; non-PSI 5.37° ± 4.43; P = .054) were found between groups. No difference in the rate of outliers (>10° error) was noted in inclination (P = .135) or version (P = .445) between groups. Greater planned version correction was correlated with greater error when PSI was utilized (PSI r = 0.519, P = .013; non-PSI r = 0.362, P = .089)., Conclusion: Both PSI and 3D computer-assisted planning without PSI (non-PSI) appear to be useful techniques to achieve version and inclination correction among patients undergoing RSA with severe glenoid deformity required glenoid bone grafting with no clear superiority of one method over the other. Surgeons should be aware that when utilizing PSI, slightly greater error in achieving version goals may occur as version correction is increased., (Copyright © 2024 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.)

Background: The purpose of this study was to evaluate the relationship between multiple radiographic measures of lateralization and distalization and clinical outcome scores after a reverse total shoulder arthroplasty (RTSA)., Methods: We retrospectively evaluated all RTSAs performed by the senior author between January 1, 2007, and November 1, 2017. We then evaluated the visual analog scale for pain (VAS pain), Simple Shoulder Test (SST), and American Shoulder and Elbow Surgeons (ASES) scores and complication and reoperation rates at a minimum of 2-year follow-up. We measured preoperative and postoperative (2-week) radiographs for the lateralization shoulder angle (LSA), the distalization shoulder angle (DSA), lateral humeral offset, and the distance from the glenoid to the lateral aspect of the greater tuberosity. A multivariable analysis was performed to evaluate the effect of the postoperative radiographic measurements on final patient-reported outcomes (ASES scores, SST, and VAS pain)., Results: The cohort included 216 shoulders from unique patients who had patient-reported outcome scores available at a minimum of 2-year follow-up (average, 4.0 ± 1.9 years) for a total follow-up rate of 70%. In the multivariable models, more lateralization (LSA) was associated with worse final ASES scores -0.52 (95% confidence interval [CI]: -0.88, -0.17; P = .004), and more distalization (DSA) was associated with better final ASES scores 0.40 (95% CI: 0.11, 0.69; P = .007). More lateralization (LSA) was associated with worse final SST scores -0.06 (95% CI: -0.11, -0.003; P = .039). Finally, greater distalization (DSA) was associated with lower final VAS pain scores, ratio = 0.98 (95% CI: 0.96, 1.00; P = .021)., Conclusions: Greater distalization and less lateralization are associated with better function and less pain after a Grammont-style RTSA. When using a Grammont-style implant, remaining consistent with Grammont's principles of implant placement will afford better final clinical outcomes., (Copyright © 2024 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.)

Background: The purpose of this study was to determine whether preoperative planning software (PPS) accurately predicts clinical range of motion (ROM) in patients with reverse total shoulder arthroplasty 1 year postoperatively with preoperative and postoperative computed tomography (CT) scans., Methods: This was a retrospective study of 16 reverse total shoulder arthroplasty patients with preoperative and postoperative (CT) scans obtained at least 1 year postoperatively. Clinical ROM was measured in abduction, external rotation at resting abduction, extension, and flexion at a minimum of 1 year postoperatively. All clinical measurements were obtained before generation of PPS ROM values. Using postoperative CT scans, the achieved implant component positions were quantified and then replicated in PPS on the preoperative CT scans. The preoperative predicted ROM was then recorded, both with and without osteophyte removal. Bland-Altman plots were generated within each motion comparing the differences between clinically measured motion and software-predicted motion., Results: The variation in clinically measured ROM in abduction, external rotation at resting abduction, extension, and flexion were 118 ± 27 (65° to 180°), 33 ± 16 (10° to 75°), 56 ± 8 (50° to 65°), and 137 ± 25 (80° to 160°), respectively. Clinically measured motion differed greatly from PPS-predicted ROM, with mean differences of 33 ± 29 (-32 to 93) for abduction, 44 ± 25 (-38 to 57) for external rotation, 44 ± 25 (-35 to 65) for extension, and 54 ± 50 (-51 to 147) for flexion with no significant correlations between clinically measured and PPS-predicted ROM ( P > 0.05). With humeral or humeral and glenoid osteophyte resection, correlations for only flexion became significant ( P = 0.002 for both)., Conclusion: The passive glenohumeral impingement-free ROM generated from PPS incompletely predicts clinically measured active humerothoracic ROM, possibly because of the unmeasured factors of soft-tissue tension, muscular strength, humeral torsion, resting scapular posture, and, most importantly, scapulothoracic motion., Level of Evidence: IV., (Copyright © 2023 by the American Academy of Orthopaedic Surgeons.)

Background: Common genetic variants with small effect sizes have been associated with rotator cuff tearing although very few rare, highly penetrant variants have been identified. The purpose of this pilot study was to identify dominant coding variants that segregated with affected individuals in pedigrees at high risk for rotator cuff tears (RCTs). We hypothesize that rare variants contribute to symptomatic RCTs and that they can be identified in related cases with a full-thickness tear requiring surgical management., Methods: We used the Utah Population Database to identify pedigrees that exhibited a significant excess of individuals who had undergone surgical repair of a full-thickness RCT. We analyzed whole exome sequence analysis to identify rare coding variants in 9 independent affected cousin pairs (first or second cousins) who had undergone arthroscopic surgery for repair of a full-thickness RCT (mean age at diagnosis 68 years). Validation of association of the candidate variants with risk for rotator cuff tearing was accomplished utilizing data from the UK Biobank and a separate cohort of unrelated cases of full-thickness RCTs., Results: A total of 82 rare (minor allele frequency <0.005) coding variants were identified as shared in at least one cousin pair affected with full-thickness rotator cuff tearing belonging to a high-risk pedigree, which included variants in RUNX1, ADAM12 , TGFBR2 , APBB1 , PDLIM7, LTBP1 , MAP3K4, and MAP3K1 . Analysis of 39 of these variants with data available in the UK Biobank (3899 cases with rotator cuff injury and 11,697 matched controls; mean case age 59.9 years) identified a significant association with the APBB1 gene (OR = 2.37, P  = .007, uncorrected). The PDLIM7 allele was found to be in significant excess in RCT cases in a separate cohort of Utah patients with full-thickness RCTs (10 carriers out of 458 independent, unrelated patients; minor allele frequency of 0.022) compared to a minor allele frequency of 0.0058 for the European (non-Finnish) control population rate (749 carriers out of 128612 tested) (chi-square test: 19.3 [ P  < .001])., Discussion: The analysis of closely related individuals with confirmed full-thickness RCTs from high-risk pedigrees has identified 82 rare, shared candidate genetic predisposition coding variants. Association of the PDLIM7 allele with risk for tear was confirmed in an independent cohort of RCTs. Further analysis of the variant alleles is required for confirmation of these genes in rotator cuff tearing., (© 2024 The Authors.)

Failure of healing after rotator cuff repair (RCR) is common. The purpose of the current study was to evaluate the effect of systemic estrogen or testosterone supplementation on tendon healing after RCR. Seventy-two adult male mice were utilized for all experiments. The supraspinatus tendon was transected and repaired with 6-0 Prolene suture on the left shoulder of 51 animals. Mice were segregated into three groups postoperative: (1) vehicle group (VG; n = 18), (2) estrogen group (EST; n = 17), and (3) testosterone group (TST; n = 16). An unrepaired control group (unrepaired, n = 21) did not have surgery. Utilizing these animals, histological analysis, activity testing, biomechanical testing and RNA sequencing (RNA-seq) was performed. At 8 weeks post-RCR, TST, and EST supplementation improved the overall histologic structure of the repaired enthesis site. No differences in ultimate failure loads or stiffness were detected between VG, EST, and TST groups after biomechanical testing. RCR caused a reduction in wheel activity compared to unrepaired controls and supplementation with TST restored wheel activity. RNA-seq analysis indicated that estrogen and testosterone regulated different pathways associated with enthesis healing, including a suppression of inflammatory signaling. Supplementation with sex hormones improved the structure of the repaired tendon enthesis and significantly regulated expression of diverse pathways regulating multiple biological processes. Testosterone administration following RCR restored wheel activity without having a detrimental impact on biomechanical strength. Future human studies of sex hormone supplementation after RCR are warranted as supplementation in an animal model may improve tendon enthesis healing., (© 2023 Orthopaedic Research Society.)