Muscle architectural changes after massive human rotator cuff tear

Rotator cuff (RC) tendon tears lead to negative structural and functional changes in the associated musculature. The structural features of muscle that predict function are termed “muscle architecture.” Although the architectural features of “normal” rotator cuff muscles are known, they are poorly understood in the context of cuff pathology. The purpose of this study was to investigate the effects of tear and repair on RC muscle architecture. To this end thirty cadaveric shoulders were grouped into one of four categories based on tear magnitude: Intact, Full‐thickness tear (FTT), Massive tear (MT), or Intervention if sutures or hardware were present, and key parameters of muscle architecture were measured. We found that muscle mass and fiber length decreased proportionally with tear size, with significant differences between all groups. Conversely, sarcomere number was reduced in both FTT and MT with no significant difference between these two groups, in large part because sarcomere length was significantly reduced in MT but not FTT. The loss of muscle mass in FTT is due, in part, to subtraction of serial sarcomeres, which may help preserve sarcomere length. This indicates that function in FTT may be impaired, but there is some remaining mechanical loading to maintain “normal” sarcomere length‐tension relationships. However, the changes resulting from MT suggest more severe limitations in force‐generating capacity because sarcomere length‐tension relationships are no longer normal. The architectural deficits observed in MT muscles may indicate deeper deficiencies in muscle adaptability to length change, which could negatively impact RC function despite successful anatomical repair. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:2089–2095, 2016.     

Muscle stem cell activation in a mouse model of rotator cuff injury

Rotator cuff (RC) tears are frequently complicated by muscle atrophy. Muscle stem cells (MuSCs) repair damaged myofibers following injury, but their role in the prevention or pathogenesis of atrophy following RC tears remains undefined. We hypothesized that the RC MuSC population would be affected by supraspinatus (SS) and infraspinatus (IS) tendon transection (TT) compared to uninjured muscle in a mouse model of RC tear. C57BL6/J mice underwent unilateral SS and IS TT and contralateral sham surgery. At 3, 8, or 14 weeks after injury, mice were euthanized, and SS and IS were harvested for FACS sorting of CD31‐/CD45‐/Sca1‐/ITGa7+/VCAM+ MuSCs or histological analysis. Ki‐67+ MuSCs from injured muscle increased 3.4‐fold at 3 weeks (p = 0.03) and 8.1‐fold at 8 weeks (p = 0.04) following TT injury, but returned to baseline by 14 weeks (p = 0.91). Myod1 remained upregulated 3.3‐fold at 3 weeks (p = 0.03) and 2.0‐fold at 14 weeks (p = 0.0003), respectively. Myofiber cross‐sectional area was decreased at both 3 and 14 weeks after injury, but the number of MuSCs per fiber remained relatively constant at 3 (p = 0.3) and 14 (p = 0.6) weeks after TT. In this study, we characterized the longitudinal effect of RC tendon injury on the MuSC population in supraspinatus and infraspinatus muscles. MuSCs are transiently activated, and are not depleted, in spite of persistent muscle atrophy. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1370–1376, 2018.

     

The effects of chronic unloading and gap formation on tendon‐to‐bone healing in a rat model of massive rotator cuff tears

The objective of this study was to understand the effect of pre‐repair rotator cuff chronicity on post‐repair healing outcomes using a chronic and acute multi‐tendon rat rotator cuff injury model. Full‐thickness dual tendon injuries (supra‐ and infraspinatus) were created unilaterally in adult male Sprague Dawley rats, and left chronically detached for 8 or 16 weeks. After chronic detachment, tears were repaired and acute dual tendon injuries were created and immediately repaired on contralateral shoulders. Tissue level outcomes for bone, tendon, and muscle were assessed 4 or 8 weeks after repair using histology, microcomputed tomography, biomechanical testing, and biochemical assays. Substantial gap formation was seen in 35% of acute repairs and 44% of chronic repairs. Gap formation negatively correlated with mechanical and structural outcomes for both healing time points regardless of injury duration. Bone and histomorphometry, as well as biomechanics, were similar between acute and chronic injury and repair regardless of chronicity and duration of healing. This study was the first to implement a multi‐tendon rotator cuff injury with surgical repair following both chronic and acute injuries. Massive tear in a rodent model resulted in gap formation regardless of injury duration which had detrimental effects on repair outcomes. © 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:439–447, 2014.     

Muscle Fibers are Injured at the Time of Acute and Chronic Rotator Cuff Repair

BackgroundRotator cuff tears are a common source of shoulder pain and disability. Even after surgical repair, some patients continue to have reduced function and progression of fatty degeneration. Because patients with chronic cuff tears often experience muscle shortening, it is possible that repairing the tendon to its anatomic footprint induces a stretch-induced muscle injury that could contribute to failures of the repair and perhaps ongoing pain.Questions/purposesWe hypothesized that, compared with acutely torn and repaired muscles, the stretch that is required to repair a chronically torn cuff would result in more muscle fiber damage. Specifically, we asked: (1) Is there muscle fiber damage that occurs from repair of an acutely torn rotator cuff and does it vary by location in the muscle; and (2) is the damage greater in the case of repair of a chronic injury?MethodsWe used an open surgical approach to create a full-thickness rotator cuff tear in rats, and measured changes in muscle mass, length, and the number of fibers containing the membrane impermeable Evans Blue Dye after acute (1 day) or chronic (28 days) cuff tear or repair in rats. Differences between groups were tested using a one-way ANOVA followed by Tukey’s post hoc sorting.ResultsChronic tears resulted in 24% to 35% decreases in mass and a 20% decrease in length. The repair of acutely and chronically torn muscles resulted in damage to 90% of fibers in the distal portion of the muscle. In the proximal portion, no differences between the acutely torn and repaired groups and controls were observed, whereas repairing the chronically torn group resulted in injury to almost 70% of fibers.ConclusionsIn a rat model, marked injury to muscle fibers is induced when the tendons of torn rotator cuffs are repaired to their anatomic footprint.

Clinical Relevance

In this animal model, we found that repair of chronically torn cuff muscles results in extensive injury throughout the muscle. Based on these findings, we posit that inducing a widespread injury at the time of surgical repair of chronically torn rotator cuff muscles may contribute to the problems of failed repairs or continued progression of fatty degeneration that is observed in some patients that undergo rotator cuff repair. Therapeutic interventions to protect muscle fiber membranes potentially could enhance outcomes for patients undergoing rotator cuff repair. To evaluate this, future studies that evaluate the use of membrane sealing compounds or drugs that upregulate endogenous membrane-sealing proteins are warranted.     

A rat model of massive rotator cuff tears

Rotator cuff tears (RCTs) are the most common tendon injury seen in orthopedic patients. Massive RCT does not heal spontaneously and results in poor clinical outcomes. Muscle atrophy and fatty infiltration in rotator cuff muscles are major complications of chronic massive RCT and are thought to be the key factors responsible for the failure of attempted massive RCT repair. However, the pathophysiology of rotator cuff muscle atrophy and fat infiltration remains largely unknown, and no small animal model has been shown to reproduce the histologic and molecular changes seen in massive RCT. In this article, we report a novel rat massive RCT model, in which significant and consistent muscle atrophy and fat infiltration were observed in the rotator cuff muscles after rotator cuff tendon transection and denervation. The supraspinatus and infraspinatus muscle lost 25.4% and 28.9% of their wet weight 2 weeks after complete tendon transection, respectively. Six weeks after surgery, the average wet weight of supraspinatus and infraspinatus muscles decreased 13.2% and 28.3%, respectively. Significant fat infiltration was only observed in infraspinatus 6 weeks after tendon transection. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 29:588–595, 2011     

Beige FAPs Transplantation Improves Muscle Quality and Shoulder Function After Massive Rotator Cuff Tears

Rotator cuff (RC) tears are a common cause of upper extremity disability. Any tear size can result in subsequent muscle atrophy and fatty infiltration (FI). Preoperative muscle degeneration can predict repair and postoperative functional outcomes. Muscle residential fibro-adipogenic progenitors (FAPs) are found to be capable of differentiating into beige adipocytes that release factors to promote muscle growth. This study evaluated the regenerative potential of local cell transplantation of beige FAPs to mitigate muscle degeneration in a murine massive RC tear model. Beige FAPs were isolated from muscle in UCP-1 reporter mice by flow cytometry as UCP-1⁺/Sca1⁺/PDGFR⁺/CD31⁻/CD45⁻/integrin α7⁻. C57/BL6J mice undergoing supraspinatus tendon tear with suprascapular nerve transection (TT + DN) received either no additional treatment, phosphate-buffered saline injection, or beige FAP injection 2 weeks after the initial injury. Forelimb gait analysis was used to assess shoulder function with DigiGait. Mice were sacrificed 6 weeks after cell transplantation. FI, fibrosis, fiber size, vascularity were analyzed and quantified via ImageJ. Our results showed that beige FAP transplantation significantly decreased fibrosis, FI, and atrophy, enhanced vascularization compared with saline injection and non-treatment groups. Beige FAP transplantation also significantly improved shoulder function as measured by gait analysis. This study suggests that beige-differentiated FAPs may serve as a treatment option for RC muscle atrophy and FI, thus improving shoulder function in patients with massive RC tendon tears. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:1159-1166, 2020     

Rat rotator cuff muscle responds differently from hindlimb muscle to a combined tendon‐nerve injury

Rotator cuff tears (RCTs) are among the most common musculoskeletal injuries seen by orthopaedic surgeons. Clinically, massive cuff tears lead to unique pathophysiological changes in rotator cuff muscle, including atrophy, and massive fatty infiltration, which are rarely seen in other skeletal muscles. Studies in a rodent model for RCT have demonstrated that these histologic findings are accompanied by activation of the Akt/mammalian target of rapamycin (mTOR) and transforming growth factor‐β (TGF‐β) pathways following combined tendon‐nerve injury. The purpose of this study was to compare the histologic and molecular features of rotator cuff muscle and gastrocnemius muscle—a major hindlimb muscle, following combined tendon‐nerve injury. Six weeks after injury, the rat gastrocnemius did not exhibit notable fatty infiltration compared to the rotator cuff. Likewise, the adipogenic markers SREBP‐1 and PPARγ as well as the TGF‐β canonical pathway were upregulated in the rotator cuff, but not the gastrocnemius. Our study suggests that the rat rotator cuff and hindlimb muscles differ significantly in their response to a combined tendon‐nerve injury. Clinically, these findings highlight the unique response of the rotator cuff to injury, and may begin to explain the poor outcomes of massive RCTs compared to other muscle‐tendon injuries. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:1046–1053, 2015.     

Evaluation of Akt/mTOR activity in muscle atrophy after rotator cuff tears in a rat model

Atrophy of the rotator cuff muscles is a factor that complicates the treatment of a massive rotator cuff tear (RCT). However, the molecular mechanisms that govern the development of muscle atrophy after RCTs have not been well defined. The Akt/mammalian target of rapamycin (mTOR) signaling pathway plays a central role in maintaining muscle mass in response to mechanical loading. The role of this pathway in the development of muscle atrophy after a massive RCT remains unknown. The purpose of this study was to investigate the regulation of the Akt/mTOR pathway in the development of muscle atrophy after a RCT and suprascapular nerve (SSN) injury. We evaluated the activity of the Akt/mTOR signaling pathway and how this pathway interacts with two atrophy‐related genes, MuRF‐1 and MAFbx, in supraspinatus muscles of rats that underwent unilateral complete rotator cuff tendon transection or SSN transection. Akt/mTOR activity was significantly reduced after tendon rupture, but increased after nerve injury. MuRF‐1 and MAFbx were only up‐regulated following denervation. These results suggest that tendon transection leads to a decrease in protein synthesis with down‐regulation of the Akt/mTOR signaling pathway, whereas denervation leads to an increase in protein degradation via up‐regulation of expression of MuRF‐1 and MAFbx. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 30:1440–1446, 2012     

Successful return to high level sports following early surgical repair of complete tears of the proximal hamstring tendons

The purpose of this study was to investigate the outcome of surgical management of acute complete proximal hamstring tendon tears. This was a prospective review of a case series from a tertiary referral centre. Ten patients presenting with complete proximal hamstring tendon tears were confirmed on MRI. All patients underwent surgical exploration and repair of the torn tendons with the aim of returning to normal activities and sports. Isokinetic muscle testing was performed using a dynamometer. The Cybex dynamometer (Cybex International, Ronkonkowa, NY) testing revealed almost comparable readings for the operated versus the non-operated side. An average peak torque of the operated hamstring muscles of 82.78% (range 47.16–117.88%), compared to the contralateral leg, was noted at six months. An excellent outcome was found in terms of return to normal activities and sports. Early surgical repair and physiotherapy has been noted to be associated with a good outcome and enables an early return to high level sports after complete tear of the proximal hamstring tendons.     

Rabbit supraspinatus motor endplates are unaffected by a rotator cuff tear

Rotator cuff tears are a major cause of morbidity. Following rotator cuff tears, muscle atrophy and fatty infiltration begin in the tissue, limiting repair potential and leading to a higher re‐tear rate and a worse functional outcome. We evaluated whether fatty degeneration resulting from a complete supraspinatus tear with retraction is associated with an injury to the suprascapular nerve. Four skeletally mature New Zealand white rabbits were randomized to receive an index procedure on either their right or left shoulder with the opposite shoulder serving as a control. At the index procedure, the supraspinatus tendon was transected at its insertion and allowed to retract. At 3 months, the rabbits were euthanized, and both supraspinatus muscles were harvested. The specimens were then examined with confocal microscopy and histology. Atrophy was grossly visible in all four test muscles, and fatty infiltration was confirmed with osmium tetroxide staining. In all four rabbits, the degree of denervation (p = 0.71) and partial denervation (p = 0.91) was not significantly different between control and experimental muscle. Rotator cuff tear does not affect the motor endplate or innervation status of the supraspinatus. Fatty infiltration occurs independent of denervation of the supraspinatus. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31:99–104, 2012     

Asymmetric atrophy of the supraspinatus muscle following tendon tear.

Muscle atrophy is a known consequence of muscle disuse, muscle denervation and tendon tear. Whereas after nerve injury muscle atrophies in the denervated area, the distribution of muscle atrophy following tear of its tendon is not known. Standardized MRI scans of 64 consecutive, painful shoulders were evaluated for supraspinatus tendon tearing, myotendinous retraction, supraspinatus muscle atrophy, fatty infiltration, ratio of the scapular (deep) and fascial (superficial) muscle area ("symmetry") and position of the central tendon within the supraspinatus fossa. There were thirteen shoulders with no and eleven shoulders with partial thickness supraspinatus tendon tears. In the forty cases with full thickness tendon tear, there was significant muscle atrophy and fatty infiltration. Atrophy of the fascial muscle portion was 43%, on the bony side it was 9% (p<0.005). The position of the central tendon within the supraspinatus fossa, was unaltered. Muscular changes following tendon tear occur highly asymmetrically: the muscle portion originating from the fascia primarily atrophies, the portion originating from the scapula primarily undergoes fatty infiltration. Muscular changes are not simply a consequence of muscle disuse, but dependent on architectural changes in the muscle.     

Role of biomechanical assessment in rotator cuff tear repair: Arthroscopic vs mini-open approach

BACKGROUNDRotator cuff (RC) tears are one of the most frequent pathologies within the shoulder girdle. Hand dominance and older age are associated with RC tears. Two different surgical procedures, the mini-open (MO) and all-arthroscopic (AA) approach, represented the standard of treatment.AIMTo compare the clinical and biomechanical outcomes of two surgical techniques (AA vs MO procedure) performed to address the painful shoulder syndrome with partial or total supraspinatus tendon tear.METHODSEighty-eight participants, 50 following RC repair with AA and 38 with MO approach, were recruited in the present cross-sectional case-control study (ORTHO-SHOULDER, Prot. 0054602). All patients underwent postoperative clinical evaluation for pain (Visual analogic scale), impairment, and disability (disability of the arm, shoulder, and hand) and limitation in daily activity (Constant-Murley score). Patients’ shoulder mobility was also assessed in our Laboratory of Functional Movement through a wearable inertial sensor and surface electromyography to monitor kinematics and muscle activity during the movement on the frontal (abduction/adduction) and sagittal (flexion-extension) planes.RESULTSNo statistically significant differences between the two procedures were observed in either main clinical score or range of motion. A significant increase in velocity during the movement execution and a higher contribution of upper trapezius muscles were found in the AA group compared with MO patients.CONCLUSIONIn terms of clinical scores, our findings were in line with previous results. However, the use of technology-based assessment of shoulder mobility has revealed significant differences between the two techniques in terms of mean velocity and pattern of muscle activation.     

Skeletal muscle fibrosis and stiffness increase after rotator cuff tendon injury and neuromuscular compromise in a rat model

Rotator cuff tears can cause irreversible changes (e.g., fibrosis) to the structure and function of the injured muscle(s). Fibrosis leads to increased muscle stiffness resulting in increased tension at the rotator cuff repair site. This tension influences repairability and healing potential in the clinical setting. However, the micro‐ and meso‐scale structural and molecular sources of these whole‐muscle mechanical changes are poorly understood. Here, single muscle fiber and fiber bundle passive mechanical testing was performed on rat supraspinatus and infraspinatus muscles with experimentally induced massive rotator cuff tears (Tenotomy) as well as massive tears with chemical denervation (Tenotomy + BTX) at 8 and 16 weeks post‐injury. Titin molecular weight, collagen content, and myosin heavy chain profiles were measured and correlated with mechanical variables. Single fiber stiffness was not different between controls and experimental groups. However, fiber bundle stiffness was significantly increased at 8 weeks in the Tenotomy + BTX group compared to Tenotomy or control groups. Many of the changes were resolved by 16 weeks. Only fiber bundle passive mechanics was weakly correlated with collagen content. These data suggest that tendon injury with concomitant neuromuscular compromise results in extra‐cellular matrix production and increases in stiffness of the muscle, potentially complicating subsequent attempts for surgical repair. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:1111–1116, 2014.     

Die endoskopisch subakromiale Dekompression bei artikularseitigen Supraspinatuspartialrupturen – Klinische und strukturelle Ergebnisse

Patients with primary impingement and articular sided partial tears of the supraspinatus tendon are often treated by subacromial decompression without repair, if the extent of the tear is estimated to be below 50% of tendon thickness. It has been questioned whether repair of these cuff lesions is necessary because these tears could progress to full thickness tears with deteriorating clinical results. Our hypothesis was that subacromial decompression without repair of the supraspinatus tendon leads to significant clinical improvement for patients with grades I and II articular sided tears without progression to a full thickness tear on a regular basis. A total of 46 consecutive patients (average age 59.2 years, range 33–76.6 years) were retrospectively reviewed after an average follow-up of 50.3 months (36–86 months). Of these patients 26 (43.5%) had a grade I tear according to Ellman which was not treated and 20 patients suffered from a grade II tear which was treated by intra-articular debridement. Clinical outcome was assessed with the ASES score and ultrasound evaluation was performed on all patients to detect possible progression to a full thickness tear. The average ASES score significantly improved from 37.4 to 86.6 points (p<0.0001). The mean postoperative Constant score was 87.6 points. Only three patients (6.5%) progressed to a full thickness tear detectable by ultrasound examination. Only one of these patients had a poor result with an ASES score of 35 points, the other two were very satisfied with the results and had an ASES score above 90 points. Overall clinical outcome was rated excellent in 35 cases (76.1%), good in 5 (10.9%), average in 2 (4.3%) and poor in 4 (8.7%). Our results indicate that good and excellent results can be achieved mid-term by acromioplasty without repair of the rotator cuff in articular sided partial tears of the supraspinatus tendon grades I and II. Progression to a full thickness tear was rare in our study group (6.5%) and not always associated with a poor outcome. However, with follow-up in excess of 5 years the clinical outcome was significantly worse.     

The tension required at repair to reappose the supraspinatus tendon to bone rapidly increases after injury

Rotator cuff tears occur frequently and can cause significant pain and reduced shoulder function. A high percentage of patients are satisfied after surgical repair of rotator cuff tears, but a smaller percentage of patients with chronic tears continue to have pain and poor shoulder function. This may be partly attributable to an increase in the repair tension, the force required at repair to reappose the tendon to its original insertion site on the humerus. Increases in repair tension have been shown to occur for long-standing ruptures of the supraspinatus tendon, but the precise tension at various times after injury are unknown. Therefore, the objective of the current study was to determine the repair tension at various times after a rotator cuff tear. This was achieved by creating a full-thickness supraspinatus tendon tear in a rat model and measuring the mechanical characteristics of the musculotendinous unit at 0, 2, 4, 9, and 16 weeks after injury. The repair tension rapidly increased initially after injury followed by a progressive, but less dramatic, increase with additional time. These findings suggest that rotator cuff tears should be repaired early in the clinical setting. Future studies will investigate the effect of repair tension on tendon to bone healing after repair.     

Correlations between biochemical markers in the synovial fluid and severity of rotator cuff disease

The role of biochemical factors in the onset and natural history of rotator cuff disease is not fully understood, but it is generally recognised that they could induce tendon damage in association with mechanical and vascular factors. In this study, 5 biochemical parameters were analysed (total protein concentration, matrix metalloproteinase (MMP)-2 or gelatinase A, MMP-9 or gelatinase B, type I collagen telopeptides, hyaluronic acid) in the synovial fluid (SF) aspirated from the gleno-humeral joint of 29 patients undergoing surgical therapy for rotator cuff lesions. Four different groups of patients were identified according to the severity of the lesion: partial tear of the rotator cuff, full thickness tear involving <-1 tendon, full thickness tear involving >1 tendon and cuff tear arthropathy (CTA). The total SF protein concentration progressively increased with loss of integrity of the rotator cuff, reaching the highest levels in CTA. The absolute enzymatic activity of gelatinases was greater in full thickness tears than in partial tears, while it decreased in CTA. Conversely, the ratio between gelatinases and total protein content reached the highest level in partial tears and then progressively decreased. Collagen I telopeptides were significantly increased in full thickness tears and CTA, whereas the levels of hyaluronic acid decreased with worsening of rotator cuff disease. These findings support the hypothesis that gelatinases, which are involved in physiological tendon remodelling, intervene in the evolution of rotator cuff disease, too. Increased levels of type I collagen telopeptides give evidence that tendon tears are associated with an anatomic loss of tendon tissue and not with simple tendon retraction.     

Rotator Cuff Fibro-Adipogenic Progenitors Demonstrate Highest Concentration,Proliferative Capacity,and Adipogenic Potential Across Muscle Groups

Fatty infiltration (FI) of rotator cuff (RC) muscles is common in patients with RC tears. Studies have demonstrated that fibro-adipogenic progenitors (FAPs), a population of resident muscle stem cells, are the main contributors of FI, which adversely affects muscle quality and RC repair success. Although FI is common in RC injuries, it is not frequently reported after other musculotendinous injuries. Additionally, studies have shown the development of different pathology patterns across muscle groups suggestive of intrinsic differences in cellular composition and behavior. This study evaluates FAP distribution and differentiation properties across anatomic locations in mice. Muscles from seven different anatomic locations were harvested from PDGFRα-eGFP FAP reporter mice. FAPs were quantified using histology and FACS sorting with BD Aria II with CD31⁻/CD45⁻/Integrinα7⁻/Sca-1⁺ and PDGFRα reporter signal (n = 3 per muscle). The cells were analyzed for adipogenesis using immunocytochemistry and for proliferation properties with Brdu-Ki67 staining. In a separate group of mice, RC and tibialis anterior muscles received glycerol injection and were harvested after 2 weeks for FI quantification (n = 4). One-way analysis of variance was used for statistical comparisons among groups, with significance at p < 0.05. FAPs from the RC, masseter, and paraspinal muscles were more numerous and demonstrated greater proliferative capacity and adipogenic potency than those from the tibialis anterior and gastrocnemius. The RC demonstrated significantly greater levels of FI than the tibialis anterior after glycerol-injection injury. Clinical Significance: This study suggests differences in FAP distribution and differentiation characteristics may account for the propensity to develop FI in RC tears as compared with other musculotendinous injuries. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:1113-1121, 2020