Three decades of advancements in osteoarthritis research: insights from transcriptomic, proteomic, and metabolomic studies.

OBJECTIVE: Osteoarthritis (OA) is a complex disease involving contributions from both local joint tissues and systemic sources. Patient characteristics, encompassing sociodemographic and clinical variables, are intricately linked with OA rendering its understanding challenging. Technological advancements have allowed for a comprehensive analysis of transcripts, proteomes and metabolomes in OA tissues/fluids through omic analyses. The objective of this review is to highlight the advancements achieved by omic studies in enhancing our understanding of OA pathogenesis over the last three decades. DESIGN: We conducted an extensive literature search focusing on transcriptomics, proteomics and metabolomics within the context of OA. Specifically, we explore how these technologies have identified individual transcripts, proteins, and metabolites, as well as distinctive endotype signatures from various body tissues or fluids of OA patients, including insights at the single-cell level, to advance our understanding of this highly complex disease. RESULTS: Omic studies reveal the description of numerous individual molecules and molecular patterns within OA-associated tissues and fluids. This includes the identification of specific cell (sub)types and associated pathways that contribute to disease mechanisms. However, there remains a necessity to further advance these technologies to delineate the spatial organization of cellular subtypes and molecular patterns within OA-afflicted tissues. CONCLUSIONS: Leveraging a multi-omics approach that integrates datasets from diverse molecular detection technologies, combined with patients' clinical and sociodemographic features, and molecular and regulatory networks, holds promise for identifying unique patient endophenotypes. This holistic approach can illuminate the heterogeneity among OA patients and, in turn, facilitate the development of tailored therapeutic interventions.

Evolution and advancements in genomics and epigenomics in OA research: How far we have come.

OBJECTIVE: Osteoarthritis (OA) is the most prevalent musculoskeletal disease affecting articulating joint tissues, resulting in local and systemic changes that contribute to increased pain and reduced function. Diverse technological advancements have culminated in the advent of high throughput "omic" technologies, enabling identification of comprehensive changes in molecular mediators associated with the disease. Amongst these technologies, genomics and epigenomics - including methylomics and miRNomics, have emerged as important tools to aid our biological understanding of disease. DESIGN: In this narrative review, we selected articles discussing advancements and applications of these technologies to OA biology and pathology. We discuss how genomics, deoxyribonucleic acid (DNA) methylomics, and miRNomics have uncovered disease-related molecular markers in the local and systemic tissues or fluids of OA patients. RESULTS: Genomics investigations into the genetic links of OA, including using genome-wide association studies, have evolved to identify 100+ genetic susceptibility markers of OA. Epigenomic investigations of gene methylation status have identified the importance of methylation to OA-related catabolic gene expression. Furthermore, miRNomic studies have identified key microRNA signatures in various tissues and fluids related to OA disease. CONCLUSIONS: Sharing of standardized, well-annotated omic datasets in curated repositories will be key to enhancing statistical power to detect smaller and targetable changes in the biological signatures underlying OA pathogenesis. Additionally, continued technological developments and analysis methods, including using computational molecular and regulatory networks, are likely to facilitate improved detection of disease-relevant targets, in-turn, supporting precision medicine approaches and new treatment strategies for OA.

Inflammation in osteoarthritis: the latest progress and ongoing challenges.

PURPOSE OF REVIEW: The understanding of inflammation in osteoarthritis is rapidly evolving. This review highlights important basic science, mechanistic, and clinical findings since 2020 that underscore the current notion of osteoarthritis as an inflammatory disease. RECENT FINDINGS: There exists a disconnect between clinical radiographic findings and patient symptoms in osteoarthritis. Inflammation, in particular synovitis, has been put forward as a potential explanation for this disconnect. New findings have shed light on the temporal dynamics and activation states of joint-resident or systemically derived immune cell populations, notably macrophages, that participate in the inflammatory response. The intricate crosstalk in which they engage may underpin disparate pain and symptoms in patients, for instance during osteoarthritis flares. The role of biological and environmental factors such as exercise, age, and diet, have been the subject of recent studies for their protective or destructive roles in osteoarthritis inflammation. Despite these advances, no disease-modifying osteoarthritis treatments targeting inflammation have emerged. SUMMARY: Osteoarthritis is a debilitating chronic disease that manifests with widely varying symptomatology. Inflammation is now appreciated as a key pathophysiological process in osteoarthritis, but there remain considerable gaps in our understanding of its role in disease progression and how best to target the inflammatory response for therapeutic interventions.

Macrophage-mediated PDGF Activation Correlates With Regenerative Outcomes Following Musculoskeletal Trauma.

OBJECTIVE: Our objective was to identify macrophage subpopulations and gene signatures associated with regenerative or fibrotic healing across different musculoskeletal injury types. BACKGROUND: Subpopulations of macrophages are hypothesized to fine tune the immune response after damage, promoting either normal regenerative, or aberrant fibrotic healing. METHODS: Mouse single-cell RNA sequencing data before and after injury were assembled from models of musculoskeletal injury, including regenerative and fibrotic mouse volumetric muscle loss (VML), regenerative digit tip amputation, and fibrotic heterotopic ossification. R packages Harmony , MacSpectrum , and Seurat were used for data integration, analysis, and visualizations. RESULTS: There was a substantial overlap between macrophages from the regenerative VML (2 mm injury) and regenerative bone models, as well as a separate overlap between the fibrotic VML (3 mm injury) and fibrotic bone (heterotopic ossification) models. We identified 2 fibrotic-like (FL 1 and FL 2) along with 3 regenerative-like (RL 1, RL 2, and RL 3) subpopulations of macrophages, each of which was transcriptionally distinct. We found that regenerative and fibrotic conditions had similar compositions of proinflammatory and anti-inflammatory macrophages, suggesting that macrophage polarization state did not correlate with healing outcomes. Receptor/ligand analysis of macrophage-to-mesenchymal progenitor cell crosstalk showed enhanced transforming growth factor ß in fibrotic conditions and enhanced platelet-derived growth factor signaling in regenerative conditions. CONCLUSION: Characterization of macrophage subtypes could be used to predict fibrotic responses following injury and provide a therapeutic target to tune the healing microenvironment towards more regenerative conditions.

Synovial fibroblasts assume distinct functional identities and secrete R-spondin 2 in osteoarthritis.

OBJECTIVES: Synovium is acutely affected following joint trauma and contributes to post-traumatic osteoarthritis (PTOA) progression. Little is known about discrete cell types and molecular mechanisms in PTOA synovium. We aimed to describe synovial cell populations and their dynamics in PTOA, with a focus on fibroblasts. We also sought to define mechanisms of synovial Wnt/ß-catenin signalling, given its emerging importance in arthritis. METHODS: We subjected mice to non-invasive anterior cruciate ligament rupture as a model of human joint injury. We performed single-cell RNA-sequencing to assess synovial cell populations, subjected Wnt-GFP reporter mice to joint injury to study Wnt-active cells, and performed intra-articular injections of the Wnt agonist R-spondin 2 (Rspo2) to assess whether gain of function induced pathologies characteristic of PTOA. Lastly, we used cultured fibroblasts, macrophages and chondrocytes to study how Rspo2 orchestrates crosstalk between joint cell types. RESULTS: We uncovered seven distinct functional subsets of synovial fibroblasts in healthy and injured synovium, and defined their temporal dynamics in early and established PTOA. Wnt/ß-catenin signalling was overactive in PTOA synovium, and Rspo2 was strongly induced after injury and secreted exclusively by Prg4hi lining fibroblasts. Trajectory analyses predicted that Prg4hi lining fibroblasts arise from a pool of Dpp4+ mesenchymal progenitors in synovium, with SOX5 identified as a potential regulator of this emergence. We also showed that Rspo2 orchestrated pathological crosstalk between synovial fibroblasts, macrophages and chondrocytes. CONCLUSIONS: Synovial fibroblasts assume distinct functional identities during PTOA in mice, and Prg4hi lining fibroblasts secrete Rspo2 that may drive pathological joint crosstalk after injury.

Sexual dimorphism of the synovial transcriptome underpins greater PTOA disease severity in male mice following joint injury.

OBJECTIVE: Osteoarthritis (OA) is a disease with sex-dependent prevalence and severity in both human and animal models. We sought to elucidate sex differences in synovitis, mechanical sensitization, structural damage, bone remodeling, and the synovial transcriptome in the anterior cruciate ligament rupture (ACLR) mouse model of post-traumatic OA (PTOA). DESIGN: Male and female 12-week-old C57/BL6J mice were randomized to Sham or noninvasive ACLR with harvests at 7d or 28d post-ACLR (n = 9 per sex in each group - Sham, 7d ACLR, 28d ACLR). Knee hyperalgesia, mechanical allodynia, and intra-articular matrix metalloproteinase (MMP) activity (via intravital imaging) were measured longitudinally. Trabecular and subchondral bone (SCB) remodeling and osteophyte formation were assessed by µCT. Histological scoring of PTOA, synovitis, and anti-MMP13 immunostaining were performed. NaV1.8-Cre;tdTomato mice were used to document localization and sprouting of nociceptors. Bulk RNA-seq of synovium in Sham, 7d, and 28d post-ACLR, and contralateral joints (n = 6 per group per sex) assessed injury-induced and sex-dependent gene expression. RESULTS: Male mice exhibited more severe joint damage at 7d and 28d and more severe synovitis at 28d, accompanied by 19% greater MMP activity, 8% lower knee hyperalgesia threshold, and 43% lower hindpaw withdrawal threshold in injured limbs compared to female injured limbs. Females had injury-induced catabolic responses in trabecular and SCB, whereas males exhibited 133% greater normalized osteophyte volume relative to females and sclerotic remodeling of trabecular and SCB. NaV1.8+ nociceptor sprouting in SCB and medial synovium was induced by injury and comparable between sexes. RNA-seq of synovium demonstrated similar injury-induced transcriptomic programs between the sexes at 7d, but only female mice exhibited a transcriptomic signature indicative of synovial inflammatory resolution by 28d, whereas males had persistent pro-inflammatory, pro-fibrotic, pro-neurogenic, and pro-angiogenic gene expression. CONCLUSION: Male mice exhibited more severe overall joint damage and pain behavior after ACLR, which was associated with persistent activation of synovial inflammatory, fibrotic, and neuroangiogenic processes, implicating persistent synovitis in driving sex differences in murine PTOA.

Early patellofemoral cartilage and bone pathology in a rat model of noninvasive anterior cruciate ligament rupture.

OBJECTIVE: Anterior cruciate ligament rupture (ACLR) is a risk factor for the development of post-traumatic osteoarthritis (PTOA). While PTOA in the tibiofemoral joint compartment is well-characterized, very little is known about pathology in the patellofemoral compartment after ACL injury. Here, we evaluated the extent to which ACLR induces early patellofemoral joint damage in a rat model. METHODS: Adult female Lewis rats were randomized to noninvasive ACLR or Sham. Two weeks post-injury, contrast-enhanced micro-computed tomography (µCT) of femoral and patellar cartilage was performed using 20% v/v ioxaglate. Morphometric parameters of femoral trochlear and patellar cartilage, subchondral bone, and trabecular bone were derived from µCT. Sagittal Safranin-O/Fast-Green-stained histologic sections were graded using the OARSI score in a blinded fashion. RESULTS: Cartilage and bone remodelling consistent with an early PTOA phenotype were observed in both femoral trochleas and patellae. ACLR caused osteophyte formation of the patella and pathology in the superficial zone of articular cartilage, including surface fibrillation, fissures, increased cellularity, and abnormal chondrocyte clustering. There were significant increases in thickness of patellar and trochlear cartilage. Loss of subchondral bone thickness, bone volume fraction, and tissue mineral density, as well as changes to patellar and trochlear trabecular microarchitecture, were indicative of catabolic bone remodelling. Several injury-induced changes, including increased cartilage thickness and trabecular spacing and decreased trabecular number were more severe in the patella compared to the trochlea. CONCLUSION: The patellofemoral joint develops mild but evident pathology in the early period following ACL rupture, extending the utility of this model to the study of patellofemoral PTOA.

An efficient R1ρ dispersion imaging method for human knee cartilage using constant magnetization prepared turbo-FLASH.

This work aimed to develop an efficient R1ρ dispersion imaging method for clinical studies of human knee cartilage at 3 T. Eight constant magnetizations (Mprep ) were prepared by tailoring both the duration and amplitude (ω1 ) of a fully refocused spin-lock preparation pulse. The limited Mprep dynamic range was expanded by the measure, equivalent to that with ω1 = ∞, from the magic angle location in the deep femoral cartilage. The developed protocol with Mprep = 60% was demonstrated on one subject's bilateral and two subjects' unilateral asymptomatic knees. The repeatability of the proposed protocol was estimated by two repeated scans with a three-month gap for the last two subjects. The synthetic R1ρ and R2 derived from R1ρ dispersions were compared with the published references using state-of-the-art R1ρ and R2 mapping (MAPSS). The proposed protocol demonstrated good (<5%) repeatability quantified by the intra- and intersubject coefficients of variation in the femoral and tibial cartilage. The synthetic R1ρ (1/s) and the references were comparable in the femoral (23.0 ± 5.3 versus 24.1 ± 3.8, P = 0.67) and the tibial (29.1 ± 8.8 versus 27.1 ± 5.1, P = 0.62), but not the patellar (16.5 ± 4.9 versus 22.7 ± 1.6, P < 0.01) cartilage. The same trends were also observed for the current and the previous R2 . In conclusion, the developed R1ρ dispersion imaging scheme has been revealed to be not only efficient but also robust for clinical studies of human knee cartilage at 3 T.

Longitudinal characterization of intervertebral disc remodeling following acute annular injury in a rat model of degenerative disc disease.

Objective: Characterize 3D remodeling of the rat intervertebral disc (IVD) following acute annular injury via in vivo micro-computed tomography (µCT), ex vivo contrast-enhanced (CE)-µCT, and histology. Design: Female Lewis rats (N = 4/group) underwent either sham surgery or anterior annular puncture to L3-L4 and L5-L6 (n = 8 IVDs/group) to induce IVD degeneration. Rats were allowed ad libidum cage activity before and after surgery and underwent in vivo µCT scanning at baseline and every 2 weeks post-op for 12 weeks to characterize longitudinal changes in IVD height. At 12 weeks, lumbar spines were dissected and underwent CE-µCT scanning to characterize endpoint glycosaminoglycan distribution and nucleus pulposus (NP) volume ratio. Spines were processed for safranin-O-stained sagittal histology, and IVD degeneration was graded via the Rutges scale. Results: Puncture IVDs exhibited loss of IVD height at all time points from 4 weeks onward compared to Sham-the most severe height loss occurred posteriorly, with significant changes also occurring in the NP and laterally. Puncture IVDs exhibited higher CE-µCT attenuation, indicative of lower glycosaminoglycan content, and reduced NP volume ratio compared to Sham. Histologically, Puncture IVDs had higher Rutges damage scores and exhibited reduced NP cellularity and hydration, disorganized annulus fibrosus (AF) lamellae with evidence of the stab tract, and indistinct AF-NP border compared to Sham. Conclusions: Characterization of the complex, 3D alterations involved in the onset and early progression of IVD degeneration can foster greater understanding of the pathoetiology of IVD degeneration and may inform future studies assessing more sensitive diagnostic techniques or novel therapies.

Vault perforation after eccentric glenoid reaming for deformity correction in anatomic total shoulder arthroplasty.

BACKGROUND: The management of glenoid deformity during anatomic total shoulder arthroplasty remains controversial. In this study, we evaluate variable correction of glenoid deformity by eccentric reaming. We hypothesize that partial correction of modified Walch B/C-type glenoid deformities can achieve 75% bone-implant contact area (BICA) with a reduced vault perforation risk compared with complete correction. METHODS: Fifty shoulder computed tomographic scans with glenohumeral osteoarthritis were retrospectively evaluated. The Tornier BluePrint v2.1.5 software simulated 3 eccentric reaming scenarios including no, partial, and complete deformity correction. Each scenario was evaluated at 4 BICAs and using 3 implant fixation types. Three-dimensional surface representations were used to evaluate medialization and vault perforation. RESULTS: The patients had mean glenoid retroversion and inclination of 18.5° and 8.8°, respectively, and mean posterior humeral head subluxation of 76%. With 75% BICA, the 3 fixation types had glenoid vault perforation in 6%-26% and 26%-54% of cases for partial and complete glenoid deformity correction, respectively. The central and posterior-inferior implant components were most likely to perforate across all scenarios. DISCUSSION: Eccentric reaming for glenoid deformity correction increases the risk of vault perforation. Severe glenoid deformity required increased medialization to achieve 75% BICA. Pegged implants have increased chances of perforation compared with a keeled design; the central and posterior-inferior components were most likely to perforate during deformity correction. CONCLUSION: Partial deformity correction of modified Walch B/C-type glenoid deformities can achieve 75% BICA while reducing the risk of vault perforation compared with complete correction at the time of anatomic total shoulder arthroplasty.

Biomechanical properties of the repaired and non-repaired rat supraspinatus tendon in the acute postoperative period.

PURPOSE: The rat rotator cuff (RC) model is used to study RC pathology and potential treatment; however, native scar-mediated healing allows the rat RC to recover at 4-6 weeks but little is known about acute healing. This study characterized the properties of the repaired and non-repaired rat RC following surgical detachment. MATERIALS AND METHODS: Forty-eight rats underwent surgical RC detachment and received surgical repair (Repair) or left unrepaired (Defect) to either 12 or 19 days. Healthy controls were obtained from contralateral limbs. Biomechanical properties were assessed using stress relaxation and failure testing and mechanical modeling performed using quasilinear viscoelastic (QLV) and structurally based elastic models. Histology and micro-magnetic resonance imaging were used to qualitatively grade tendon-to-bone healing. RESULTS: Repair and Defect exhibited significantly inferior mechanical properties compared to Healthy at both time points. Repair had significant increases in peak, equilibrium, and ultimate stress, modulus, and stiffness and significant decreases in cross-sectional area, % relaxation, and QLV constant "C" between 12 and 19 days, whereas Defect showed no change. CONCLUSIONS: This study demonstrates acute differences in mechanical properties of the rat supraspinatus tendon in the presence and absence of surgical repair. Understanding the longitudinal recovery of mechanical properties can facilitate more accurate characterization of RC pathology or future treatments.

Exposure of articular chondrocytes to wear particles induces phagocytosis, differential inflammatory gene expression, and reduced proliferation.

The production of wear debris particulate remains a concern due to its association with implant failure through complex biologic interactions. In the setting of unicompartmental knee arthroplasty (UKA), damage and wear of the components may introduce debris particulate into the adjacent, otherwise, healthy compartment. The purpose of this study was to investigate the in vitro effect of polymeric and metallic wear debris particles on cell proliferation, extracellular matrix regulation, and phagocytosis index of normal human articular chondrocytes (nHACs). In culture, nHACs were exposed to both cobalt-chromium-molybdenum (CoCrMo) and polymethyl-methacrylate (PMMA) wear debris particulate for 3 and 10 days. At 3 days, no significant difference in cell proliferation was found between control cells and cells exposed to both CoCrMo or PMMA particles. However, cell proliferation was significantly decreased for CoCrMo exposed nHACs at both 6 (P < 0.001) and 10 days (P < 0.001) and PMMA at 10 days (P < 0.001). Target gene expression displayed both a time- and material-dependent response to CoCrMo and PMMA particles. Significant differences in COL10A1, ACAN, VCAN, IL-1ß, TNF-α, MMP3, ADAMTS1, CASP3, and CASP9 regulation were found between CoCrMo and PMMA exposed nHACs at day 3 with gene regulation returning to near baseline at 10 days. Results from our study indicate a role of wear debris induced cartilage degeneration after exposure to polymeric and metallic wear debris particulate, suggesting an additional pathway of cartilage breakdown, potentially manifesting in traditional clinical symptoms.

In vivo bone formation by and inflammatory response to resorbable polymer-nanoclay constructs.

The development of synthetic bone grafts with requisite mechanical and morphological properties remains a key challenge in orthopaedics. Supercritical carbon dioxide (scCO2)-processed nanocomposites consisting of organically-modified montmorillonite clay dispersed in poly-d-lactide (PDLA) have shown structural and mechanical properties similar to corticocancellous bone. Using quantitative undecalcified histology and micro-computed tomography (µCT), time and material-dependent influences on in vivo bone formation, and inflammatory response were characterized. This represents the first in vivo evidence of the ability of scCO2-processed PDLA-nanoclay constructs to support osteogenesis, while eliciting an inflammatory response comparable to PDLA-hydroxyapatite materials. Histologic analyses demonstrated that the in vivo performance of nanoclay-containing PDLA constructs was similar to pure PDLA constructs, though nanocomposites demonstrated more radiodense bone at all time points (µCT analysis), and higher bone volume at 6 weeks. Taken with previous structural and mechanical studies, these in vivo analyses suggest that scCO2-processed, polymer-clay nanocomposites may be suitable structural bone graft materials. FROM THE CLINICAL EDITOR: With advances in science, orthopedic researchers have devoted significant amount of time in developing synthetic bone graft materials. Many of which are indeed currently in clinical use. In their previous studies, the authors described and studied supercritical carbon dioxide (scCO2)-processed nanocomposites consisting of organically modified montmorillonite clay dispersed in poly-D-lactide (PDLA) in in-vitro experiments. Here, in-vivo experiments were performed to investigate if this new material had improved mechanical properties, as well as the induction of inflammatory response. The overall positive findings may mean that this material could be used for future bone graft substitute applications.

The effect of granulocyte-colony stimulating factor on rotator cuff healing after injury and repair.

BACKGROUND: The failure rate of tendon-bone healing after repair of rotator cuff tears remains high. A variety of biologic- and cell-based therapies aimed at improving rotator cuff healing have been investigated, and stem cell-based techniques have become increasingly more common. However, most studies have focused on the implantation of exogenous cells, which introduces higher risk and cost. We aimed to improve rotator cuff healing by inducing endogenous stem cell mobilization with systemic administration of granulocyte-colony stimulating factor (G-CSF). QUESTIONS/PURPOSES: We asked: (1) Does G-CSF administration increase local cellularity after acute rotator cuff repair? (2) Is there histologic evidence that G-CSF improved organization at the healing enthesis? (3) Does G-CSF administration improve biomechanical properties of the healing supraspinatus tendon-bone complex? (4) Are there micro-MRI-based observations indicating G-CSF-augmented tendon-bone healing? METHODS: After creation of full-thickness supraspinatus tendon defects with immediate repair, 52 rats were randomized to control or G-CSF-treated groups. G-CSF was administered for 5 days after repair and rats were euthanized at 12 or 19 postoperative days. Shoulders were subjected to micro-MR imaging, stress relaxation, and load-to-failure as well as blinded histologic and histomorphometric analyses. RESULTS: G-CSF-treated animals had significantly higher cellularity composite scores at 12 and 19 days compared with both control (12 days: 7.40 ± 1.14 [confidence interval {CI}, 5.98-8.81] versus 4.50 ± 0.57 [CI, 3.58-5.41], p = 0.038; 19 days: 8.00 ± 1.00 [CI, 6.75-9.24] versus 5.40 ± 0.89 [CI, 4.28-6.51], p = 0.023) and normal animals (12 days: p = 0.029; 19 days: p = 0.019). There was no significant difference between G-CSF-treated animals or control animals in ultimate stress (MPa) and strain, modulus (MPa), or yield stress (MPa) and strain at either 12 days (p = 1.000, p = 0.104, p = 1.000, p = 0.909, and p = 0.483, respectively) or 19 days (p = 0.999, p = 0.964, p = 1.000, p = 0.988, and p = 0.904, respectively). There was no difference in MRI score between G-CSF and control animals at either 12 days (2.7 ± 1.8 [CI, 1.08-4.24] versus 2.3 ± 1.8 [CI, 0.49-4.17], p = 0.623) or 19 days (2.5 ± 1.4 [CI, 1.05-3.94] versus 2.3 ± 1.5 [CI, 0.75-3.91], p = 0.737). G-CSF-treated animals exhibited significantly lower relative bone volume compared with normal animals in the entire humeral head (24.89 ± 3.80 [CI, 20.17-29.60) versus 32.50 ± 2.38 [CI, 29.99-35.01], p = 0.009) and at the supraspinatus insertion (25.67 ± 5.33 [CI, 19.04-32.29] versus 33.36 ± 1.69 [CI, 31.58-35.14], p = 0.027) at 12 days. Further analysis did not reveal any additional significant relationships with respect to regional bone volume or trabecular thickness between groups and time points (p > 0.05). CLINICAL RELEVANCE: Postoperative stem cell mobilization agents may be an effective way to enhance rotator cuff repair. Future studies regarding the kinetics of mobilization, the homing capacity of mobilized cells to injured tissues, and the ability of homing cells to participate in regenerative pathways are necessary.

Preoperative deltoid size and fatty infiltration of the deltoid and rotator cuff correlate to outcomes after reverse total shoulder arthroplasty.

BACKGROUND: Reverse total shoulder arthroplasty (RTSA) allows the deltoid to substitute for the nonfunctioning rotator cuff. To date, it is unknown whether preoperative deltoid and rotator cuff parameters correlate with clinical outcomes. QUESTIONS/PURPOSES: We asked whether associations exist between 2-year postoperative results (ROM, strength, and outcomes scores) and preoperative (1) deltoid size; (2) fatty infiltration of the deltoid; and/or (3) fatty infiltration of the rotator cuff. METHODS: A prospective RTSA registry was reviewed for patients with cuff tear arthropathy or massive rotator cuff tears, minimum 2-year followup, and preoperative shoulder MRI. Final analysis included 30 patients (average age, 71±10 years; eight males, 22 females). Only a small proportion of patients who received an RTSA at our center met inclusion and minimum followup requirements (30 of 222; 14%); however, these patients were found to be similar at baseline to the overall group of patients who underwent surgery in terms of age, gender, and preoperative outcomes scores. The cross-sectional area of the anterior, middle, and posterior deltoid was measured on axial proton density-weighted MRI. Fatty infiltration of the deltoid, supraspinatus, infraspinatus, teres minor, and subscapularis were quantitatively assessed on sagittal T1-weighted MR images. Patients were followed for Constant-Murley score, American Shoulder and Elbow Surgeons (ASES) scores, subjective shoulder value, pain, ROM, and strength. Correlations of muscle parameters with all outcomes measures were calculated. RESULTS: Preoperative deltoid size correlated positively with postoperative Constant-Murley score (67.27±13.07) (ρ=0.432, p=0.017), ASES (82.64±14.25) (ρ=0.377; p=0.40), subjective shoulder value (82.67±17.89) (ρ=0.427; p=0.019), and strength (3.72 pounds±2.99 pounds) (ρ=0.454; p=0.015). Quantitative deltoid fatty infiltration (7.91%±4.32%) correlated with decreased postoperative ASES scores (ρ=-0.401; p=0.047). Quantitative fatty infiltration of the infraspinatus (30.47%±15.01%) correlated with decreased postoperative external rotation (34.13°±16.80°) (ρ=-0.494; p=0.037). CONCLUSIONS: Larger preoperative deltoid size correlates with improved validated outcomes scores, whereas fatty infiltration of the deltoid and infraspinatus may have deleterious effects on validated outcomes scores and ROM after RTSA. The current study is a preliminary exploration of this topic; future studies should include prospective enrollment and standardized MRI with a multivariate statistical approach. Quantitative information attained from preoperative imaging not only holds diagnostic value, but, should future studies confirm our findings, also might provide prognostic value. This information may prove beneficial in preoperative patient counseling and might aid preoperative and postoperative decision-making by identifying subpopulations of patients who may benefit by therapy aimed at improving muscle properties. LEVEL OF EVIDENCE: Level III, prognostic study.

A review of the anterolateral ligament of the knee: current knowledge regarding its incidence, anatomy, biomechanics, and surgical dissection.

PURPOSE: To systematically review current literature on the anterolateral ligament (ALL) of the knee. METHODS: We searched the PubMed/Medline database for publications specifically addressing the ALL. We excluded studies not written in English, studies not using human cadavers or subjects, and studies not specifically addressing the ALL. Data extraction related to the incidence, anatomy, morphometry, biomechanics, and histology of the ALL and its relation to the Segond fracture was performed. RESULTS: The incidence of the ALL ranged from 83% to 100%, and this range occurs because of small discrepancies in the definition of the ALL's bony insertions. The ALL originates anterior and distal to the femoral attachment of the lateral collateral ligament. It spans the joint in an oblique fashion and inserts between the fibular head and Gerdy tubercle on the tibia. Exact anatomic and morphometric descriptions vary in the literature, and there are discrepancies regarding the ALL's attachment to the capsule and lateral meniscus. The ALL is a contributor to tibial internal rotation stability, and histologically, it exhibits parallel, crimped fibers consistent with a ligamentous microstructure. The footprint of the ALL has been shown to be at the exact location of the Segond fracture. CONCLUSIONS: The ALL is a distinct ligamentous structure at the anterolateral aspect of the knee, and it is likely involved in tibial internal rotation stability and the Segond fracture. LEVEL OF EVIDENCE: Level IV, systematic review of anatomic and imaging studies.

Retear Rates After Arthroscopic Single-Row, Double-Row, and Suture Bridge Rotator Cuff Repair at a Minimum of 1 Year of Imaging Follow-up: A Systematic Review.

PURPOSE: To determine whether there are differences in retear rates among arthroscopic single-row, double-row, and suture bridge rotator cuff repair. METHODS: The literature was systematically reviewed for clinical outcome studies assessing arthroscopic single-row, double-row, or suture bridge rotator cuff repair. All included studies indicated the imaging-diagnosed retear rate stratified by preoperative tear size at a minimum of 1 year of follow-up, and retears were diagnosed with either magnetic resonance imaging, ultrasound, or arthrogram. Only studies with comprehensive surgical methods were included, and the repair type was confirmed by the number of rows of fixation and suture configuration. Studies from journals with an impact factor below 1.5 were excluded. Retear rates were grouped and statistically compared using χ(2) tests. RESULTS: Thirty-two studies met the inclusion criteria, yielding a total of 2,048 repairs. Double-row repair (DR) and suture bridge repair (SB) both had significantly lower retear rates than single-row repair (SR) for tears sized 1 to 3 cm (DR, P < .001; SB, P < .001), less than 3 cm (DR, P < .001; SB, P = .004), greater than 3 cm (DR, P = .016; SB, P = .003), and greater than 5 cm (DR, P = .003; SB, P = .003), as well as total retear rates (DR, P = .024; SB, P = .022). DR and SB did not differ significantly from each other in any tear size category. CONCLUSIONS: Both DR and SB have lower retear rates than SR in most tear size categories. No differences in retear rates were found between DR and SB. LEVEL OF EVIDENCE: Level IV, systematic review of Level I through IV studies.

Rehabilitation following arthroscopic rotator cuff repair: a review of current literature.

Physical rehabilitation following arthroscopic rotator cuff repair has conventionally involved a 4- to 6-week period of immobilization; there are two schools of thought regarding activity level during this period. Some authors encourage early, more aggressive rehabilitation along with the use of a continuous passive motion device; others propose later, more conservative rehabilitation. Although some studies report trends in improved early range of motion, pain relief, and outcomes scores with aggressive rehabilitation following rotator cuff repair, no definitive consensus exists supporting a clinical difference resulting from rehabilitation timing in the early stages of healing. Rehabilitation timing does not affect outcomes after 6 to 12 months postoperatively. Given the lack of information regarding which patient groups benefit from aggressive rehabilitation, individualized patient care is warranted.