Is Osteoarthritis a Vascular Disease?

Osteoarthritis (OA) is now considered as a multifaceted disease affecting various articular tissues, including cartilage, bone, synovium, and surrounding ligaments. The pathophysiology strongly implicates intricate chemical communication, primarily through cytokines, leading to the production of degradative enzymes in cartilage, inflammatory peptides in synovium, and structural changes in bone, resulting in characteristic clinical features such as joint deformities and loss of cartilage space seen on X-rays. Recent studies highlight the previously underestimated role of subchondral bone in OA, revealing its permeability to cytokines and raising questions about the influence of abnormal perfusion on OA pathophysiology, suggesting a vascular component in the disease's etiology. In essence, alterations in bone perfusion, including reduced venous outflow and intraosseous hypertension, play a crucial role in influencing the physicochemical environment of subchondral bone, impacting osteoblast cytokine expression and contributing to trabecular remodeling, changes in chondrocyte phenotype, and ultimately cartilage matrix degeneration in OA. Dynamic contrast (gadolinium) enhanced magnetic resonance imaging (DCE-MRI) was used to quantify perfusion kinetics in normal and osteoarthritic subchondral bone, demonstrating that decreased perfusion temporally precedes and spatially correlates with cartilage lesions in both young Dunkin-Hartley (D-H) guinea pigs and humans with osteoarthritis. Pharmacokinetic analysis of DCE-MRI generated data reveals decreased tracer clearance and outflow obstruction in the medial tibial plateau of osteoarthritic guinea pigs, coinciding with progressive cartilage degradation, loss of Safranin O staining, and increased expression of matrix metalloproteinases and interleukin-1. Positron emission tomographic (PET) scanning using 18F-Fluoride reveals a relationship among bone blood flow, cartilage lesions, and 18F-Fluoride influx rate in OA, highlighting the intricate relationships between decreased perfusion, altered bone metabolism, and the progression of osteoarthritis. These findings, supported by 18F-Fluoride PET data, suggest the presence of venous stasis associated with outflow obstruction, emphasizing the role of decreased subchondral bone perfusion in the pathophysiology of OA and its association with reduced osteoblast activity and advanced cartilage degeneration.

Management of Garden-I and II Femoral Neck Fractures: Perspectives on Primary Arthroplasty.

This review compares internal fixation versus arthroplasty in the treatment of nondisplaced femoral neck fractures (FNFs) calling attention to evolving areas of consensus that influence clinical decision-making. The Garden classification system, typically dichotomized into nondisplaced (types I and II) and displaced (types III and IV) fractures, has been used as a guide for surgical decision-making. Conventionally, treatment of nondisplaced FNF in the elderly has been with internal fixation, and treatment of a displaced FNF has been hemi-, or more recently total hip, arthroplasty. Studies over the last decade have raised concern over the appropriate treatment of nondisplaced FNFs due to high rates of reoperation of nondisplaced FNFs treated with internal fixation. Avascular necrosis (AVN), failure of internal fixation, secondary malunion, and pin/nail penetration through the femoral head have all been observed. Several studies have attributed fixation failure to a degree of femoral neck tilt ≥20°, either posteriorly or anteriorly as seen on the lateral X-ray. Because of these observations of fixation failures, the suggestion has been made that arthroplasty be used when the degree of posterior tilt exceeds a threshold of ≥20° tilt with the expectation of diminishing failure of fixation, decreasing the risk of reoperation and preserving function without increasing mortality rate. Frustrating additional analyses are uncertainties over the mechanisms of failure of internal fixation with ≥20° tilt and the persistently substantial 1-year mortality rate after FNF, which has not been influenced by fixation or replacement type. Due to the lack of consensus regarding the determination of the appropriate surgical intervention for nondisplaced FNFs, an improved algorithm for surgical decision-making for these fractures may prove useful.

LRP5, Bone Mass Polymorphisms and Skeletal Disorders.

The formation and maintenance of the gross structure and microarchitecture of the human skeleton require the concerted functioning of a plethora of morphogenic signaling processes. Through recent discoveries in the field of genetics, numerous genotypic variants have been implicated in pathologic skeletal phenotypes and disorders arising from the disturbance of one or more of these processes. For example, total loss-of-function variants of LRP5 were found to be the cause of osteoporosis-pseudoglioma syndrome (OPPG). LRP5 encodes for the low-density lipoprotein receptor-related protein 5, a co-receptor in the canonical WNT-ß-catenin signaling pathway and a crucial protein involved in the formation and maintenance of homeostasis of the human skeleton. Beyond OPPG, other partial loss-of-function variants of LRP5 have been found to be associated with other low bone mass phenotypes and disorders, while LRP5 gain-of-function variants have been implicated in high bone mass phenotypes. This review introduces the roles that LRP5 plays in skeletal morphogenesis and discusses some of the structural consequences that result from abnormalities in LRP5. A greater understanding of how the LRP5 receptor functions in bone and other body tissues could provide insights into a variety of pathologies and their potential treatments, from osteoporosis and a variety of skeletal abnormalities to congenital disorders that can lead to lifelong disabilities.

Ochronotic Chondropathy: A Case Report.

Endogenous ochronosis, also known as alkaptonuria, is a rare disease known for its bluish-black discoloration of the skin, sclerae, and pinnae, as well as urine that turns black upon standing. Though rarely fatal, joint degradation is a common sequela, and many patients require multiple large joint arthroplasties throughout their lifetime. Though many aspects of the pathophysiological mechanisms of the disease have been described, questions remain, such as how the initiation of ochronotic pigmentation is prompted and the specific circumstances that make some tissues more resistant to pigmentation-related damage than others. In this report, we present the case of an 83-year-old female previously diagnosed with alkaptonuria including high-quality arthroscopic images displaying the fraying of articular cartilage. We also offer a summary of the latest literature on the pathophysiological mechanisms of the disease, including cellular-level changes observed in ochronotic chondrocytes, biochemical and mechanical alterations to the cartilaginous extracellular matrix, and patterns of pigmentation and joint degradation observed in humans and mice models. With these, we present an overview of the mechanisms of ochronotic chondropathy and joint degradation as the processes are currently understood. While alkaptonuria itself is rare, it has been termed a "fundamental disease," implying that its study and greater understanding have the potential to lead to insights in skeletal biology in general, as well as more common pathologies such as osteoarthritis and their potential treatment mechanisms.

The Effect of Surgical Duration on Complications and Patient Reported Outcomes in Total Hip Replacement as Evaluated Through Multi-Surgeon Pooled FORCE Registry Data from a Tertiary Care Referral Total Joint Center.

BACKGROUND: The relationship between operative times and patient outcomes in total hip arthroplasty (THA) has not been well defined. METHODS: From January 2016 to December 2019, data were prospectively collected for THA patients in the FORCE-TJR registry and hospital EMR of an academic total-joint center. RESULTS: 1,123 patients were included. Operative times ranged from 36 to 366 minutes, with a mean operative time of 111.26+/-31.37 minutes. Unadjusted GLM showed HOOS pain, ADL, and QoL scores differed across operative times, with patients who had operative times between 106 and 120 minutes having significantly lower pain, higher function, and better quality of life at 12 months, especially compared to patients with operative times < 90 minutes. Patients who had operative times between 106 and 120 minutes had significantly better VR-12 PCS and MCS at 12 months. Although statistically significant, differences were small and did not persist after controlling for within-surgeon effects, patient socio-demographics and baseline patient-reported outcomes, suggesting that patient characteristics or within-surgeon effects may play a more significant role in these patient-reported outcomes than operative time. CONCLUSION: This study showed that among THA patients, operative times were significantly associated with patient-reported outcomes at 12 months post-operatively, but is one of many surgeon and patient-related factors with effect on THA outcome.

Metabolic Bone Disorders Are Predictors for 2-year Adverse Outcomes in Patients Undergoing 2-3 Level Anterior Cervical Discectomy and Fusion for Cervical Radiculopathy or Myelopathy.

STUDY DESIGN: Retrospective cohort study utilizing the New York statewide planning and research cooperative system. STUDY OBJECTIVE: To investigate postoperative complications of patients with metabolic bone disorders (MBDs) who undergo 2-3 levels of anterior cervical discectomy and fusion (ACDF). SUMMARY OF BACKGROUND DATA: MBDs and cervical degenerative pathologies, including cervical radiculopathy (CR) and cervical myelopathy (CM), are prevalent in the aging population. Complications with ACDF procedures can lead to increased hospitalization times, more expensive overhead, and worse patient outcomes. METHOD: Patients with CM/CR who underwent an ACDF of 2-3 vertebrae from 2009 to 2011 with a minimum 2-year follow-up were identified. Patients diagnosed with 1 or more MBD at baseline were compared with a control cohort without any MBD diagnosis. Cohorts were compared for demographics, hospital-related parameters, and 2-year medical, surgical, and overall complications. Binary multivariate logistic regression was used to identify independent predictors. RESULTS: A total of 22,276 patients were identified (MBD: 214; no-MBD: 22,062). Among MBD patients, the majority had vitamin D deficiency (n = 194, 90.7%). MBD patients were older (53.0 vs 49.7 y, P < 0.001), and with higher Deyo index (1.0 vs 0.5, P < 0.001). MBD patients had higher rates of medical complications, including anemia (6.1% vs 2.3%), pneumonia (4.7% vs 2.1%), hematoma (3.3% vs 0.7%), infection (2.8% vs 0.9%), and sepsis (3.7% vs 0.9%), as well as overall medical complications (23.8% vs 9.6%) (all, P ≤0.033). MBD patients also experienced higher surgical complications, including implant-related (5.7% vs 1.9%), wound infection (4.2% vs 1.2%), and wound disruption (0.9% vs 0.2%), and overall surgical complications (9.8% vs 3.2%) (all, P ≤0.039). Regression analysis revealed that a baseline diagnosis of MBD was independently associated with an increased risk of 2-year surgical complications (odds ratio = 2.10, P < 0.001) and medical complications (odds ratio = 1.84, P = 0.001). CONCLUSIONS: MBD as a comorbidity was associated with an increased risk of 2-year postoperative complications after 2-3 level ACDF for CR or CM.

Stimulation of Chondrogenesis in a Developmental Model of Endochondral Bone Formation by Pulsed Electromagnetic Fields.

Notable characteristics of the skeleton are its responsiveness to physical stimuli and its ability to remodel secondary to changing biophysical environments and thereby fulfill its physiological roles of stability and movement. Bone and cartilage cells have many mechanisms to sense physical cues and activate a variety of genes to synthesize structural molecules to remodel their extracellular matrix and soluble molecules for paracrine signaling. This review describes the response of a developmental model of endochondral bone formation which is translationally relevant to embryogenesis, growth, and repair to an externally applied pulsed electromagnetic field (PEMF). The use of a PEMF allows for the exploration of morphogenesis in the absence of distracting stimuli such as mechanical load and fluid flow. The response of the system is described in terms of the cell differentiation and extracellular matrix synthesis in chondrogenesis. Emphasis is placed upon dosimetry of the applied physical stimulus and some of the mechanisms of tissue response through a developmental process of maturation. PEMFs are used clinically for bone repair and have other potential clinical applications. These features of tissue response and signal dosimetry can be extrapolated to the design of clinically optimal stimulation.

Rehabilitation for Total Knee Arthroplasty: A Systematic Review.

ABSTRACT: We sought to determine the comparative benefit and harm of rehabilitation interventions for patients who have undergone elective, unilateral total knee arthroplasty for the treatment of primary osteoarthritis. We searched PubMed, Embase, The Cochrane Register of Clinical Trials, CINAHL, PsycINFO, Scopus, and ClinicalTrials.gov from January 1, 2005, through May 3, 2021. We included randomized controlled trials and adequately adjusted nonrandomized comparative studies of rehabilitation programs reporting performance-based, patient-reported, or healthcare utilization outcomes. Three researchers extracted study data and assessed risk of bias, verified by an independent researcher. The team assessed strength of evidence. Evidence from 53 studies randomized controlled trials suggests that various rehabilitation programs after total knee arthroplasty may lead to comparable improvements in pain, range of motion, and activities of daily living. Rehabilitation in the acute phase may lead to increased strength but result in similar strength when delivered in the postacute phase. No studies reported evidence of risk of harms due to rehabilitation delivered in the acute period after total knee arthroplasty; risk of harms among various postacute rehabilitation programs seems comparable. All findings were of low strength of evidence. Evaluation of rehabilitation after total knee arthroplasty needs a systematic overhaul to sufficiently guide future practice or research including the use of standardized intervention components and core outcomes.

Prehabilitation for Total Knee or Total Hip Arthroplasty: A Systematic Review.

ABSTRACT: We sought to systematically review the evidence on the benefits and harms of prehabilitation interventions for patients who are scheduled to undergo elective, unilateral total knee arthroplasty or total hip arthroplasty surgery for the treatment of primary osteoarthritis. We searched PubMed, Embase, The Cochrane Central Register of Controlled Trials, CINAHL, PsycINFO, Scopus, and ClinicalTrials.gov from January 1, 2005, through May 3, 2021. We selected for inclusion randomized controlled trials and adequately adjusted nonrandomized comparative studies of prehabilitation programs reporting performance-based, patient-reported, or healthcare utilization outcomes. Three researchers extracted study data and assessed risk of bias, verified by an independent researcher. Experts in rehabilitation content and complex interventions independently coded rehabilitation interventions. The team assessed strength of evidence. While large heterogeneity across evaluated prehabilitation programs limited strong conclusions, evidence from 13 total knee arthroplasty randomized controlled trials suggest that prehabilitation may result in increased strength and reduced length of stay and may not lead to increased harms but may be comparable in terms of pain, range of motion, and activities of daily living (all low strength of evidence). There was no evidence or insufficient evidence for all other outcomes after total knee arthroplasty. Although there were six total hip arthroplasty randomized controlled trials, there was no evidence or insufficient evidence for all total hip arthroplasty outcomes.

Rehabilitation for Total Hip Arthroplasty: A Systematic Review.

ABSTRACT: We sought to determine the comparative benefits and harms of rehabilitation interventions for patients who have undergone elective, unilateral THA surgery for the treatment of primary osteoarthritis. We searched PubMed, Embase, The Cochrane Register of Clinical Trials, CINAHL, PsycINFO, Scopus, and ClinicalTrials.gov from January 1, 2005, through May 3, 2021. We included randomized controlled trials and adequately adjusted nonrandomized comparative studies of rehabilitation programs reporting performance-based, patient-reported, or healthcare utilization outcomes. Three researchers extracted study data and assessed risk of bias, verified by an independent researcher. Experts in rehabilitation content and complex interventions independently coded rehabilitation interventions. The team assessed strength of evidence. Large heterogeneity across evaluated rehabilitation programs limited conclusions. Evidence from 15 studies suggests that diverse rehabilitation programs may not differ in terms of risk of harm or outcomes of pain, strength, activities of daily living, or quality of life (all low strength of evidence). Evidence is insufficient for other outcomes. In conclusion, no differences in outcomes were found between different rehabilitation programs after THA. Further evidence is needed to inform decisions on what attributes of rehabilitation programs are most effective for various outcomes.

Osteoporosis and Fragility Fractures.

Osteoporosis and fragility fractures (FFs) are closely intertwined as the former is a common predisposing factor to the latter. This causal relationship is due to low bone density of osteoporosis and compromised bone microarchitecture, leading to structural failure, decreased ability to withstand applied stresses, and increased propensity to fracture. Osteoporosis can be idiopathic or due to a variety of secondary causes, and numerous treatment strategies are available. FFs are common injuries among the elderly and are caused by factors both intrinsic and extrinsic to the patient. The clinical and economic significances of osteoporosis and FFs are substantial, with considerable associated morbidity and mortality, and billions spent on healthcare expenditures in the US annually. Osteoporosis and FFs are two of the most important topics related to fracture liaison services (FLSs), and their understanding is integral to appreciating the benefits an FLS can provide for patients and providers.

Monoclonal Gammopathies in a Fracture Liaison Service.

Monoclonal gammopathies are a spectrum of disorders characterized by the overproduction of plasma B-cells and immunoglobulin. Monoclonal gammopathy of uncertain significance (MGUS), a pre-malignant form of multiple myeloma, is defined by relatively low bone marrow concentration of clonal plasma cells and asymptomatic clinical presentation. New evidence, however, points to an association of MGUS with osteoporosis, microarchitectural bone deficiency, and fractures, and it has been suggested that it be renamed "Monoclonal Gammopathy of Skeletal Significance." The prevalence of MGUS in the general geriatric population is estimated to be 3-8%, while the prevalence in geriatric vertebral fracture patients is 15%, and the prevalence in all fracture patients within the Rhode Island Fracture Liaison Service is 10%. Therefore, MGUS and other monoclonal gammopathies should be suspected in all patients diagnosed with osteoporosis or an osteoporotic fracture, and patients diagnosed with monoclonal gammopathies should be evaluated for osteoporosis and fracture risk and treated appropriately.

Hyperparathyroidism in a Fracture Population.

Primary hyperparathyroidism (PHPT) is a common endocrine disorder that results in excess parathyroid hormone (PTH) secretion and hypercalcemia. PHPT is usually caused by an adenoma and its presentation is often asymptomatic, though it can negatively impact the skeleton via osteoporosis mostly affecting cortical bone and fracture. The diagnosis of PHPT is made by clinical presentation and biochemical and hormonal assessment. Surgical treatment guided by ultrasound sonography and/or 99mTc-sestamibi scintigraphy is generally curative. Normocalcemic hyperparathyroidism (NPHPT) is a variant of hyperparathyroidism defined by normal serum calcium and persistently elevated serum PTH levels. Limited data exist on NPHPT's effects on the skeleton, though current evidence suggests a positive correlation between the disorder and the presence of osteoporotic fractures. Taken together, patients affected by the various manifestations of hyperparathyroidism and their associated homeostatic disturbances represent a not insignificant portion of fracture patients seen in a fracture liaison service.

Bounding the Implications of Noncompliance in Randomized Controlled Trials in Orthopaedics: An Example in Arthroscopic Surgery.

INTRODUCTION: Randomized controlled trials (RCTs) are not impervious to bias especially when there are substantial numbers of patients who cross over from the treatment assigned by randomization to another treatment group, leading to loss of confidence in study results. The goals of this study were to (1) quantify the effects of crossovers on RCTs, (2) describe the specific effects of crossovers on RCTs for arthroscopic meniscectomy for osteoarthritis of the knee (APM/OAK), and (3) assess the confidence in APM/OAK in which there have been substantial numbers of patients crossing over to another treatment group than that assigned. METHODS: Studies were included that were RCTs of APM/OAK with intention-to-treat (ITT) analysis and illustrated the problem of crossovers on confidence in the analysis. Studies were excluded if they consisted of APM for conditions other than OAK or had unavailability of data needed for the analysis. For eligible RCTs, the ITT effect was calculated; bounds for the average treatment effect (ATE) and the complier ATE were assessed by estimating confidence intervals for the bound through robust Bayesian analysis. RESULTS: The eligible studies had different comparators and, therefore, were analyzed individually. Data were not pooled. The most extreme point estimates (with 95% confidence interval) for ITT ranged from -0.01 to 0.04 (-0.16 to 0.16); for ATE with no assumptions, 0.38 (-0.58 to 0.43) to 0.62 (0.56 to 0.70); for ATE with minimum assumptions, -0.50 (-0.22 to 0.10) to 0.61 (0.53 to 0.57); and for complier ATE, -0.01 to 0.07 (-0.22 to 0.24). DISCUSSION: These data suggest large bounds, crossing the threshold of "no effect," which indicates a high degree of uncertainty and low confidence in the RCTs studied. The results demonstrate that when there are crossovers, ITT analyses do not estimate the ATE and confidence in the results of these RCTs is low. DATA AVAILABILITY: All analyzed data are provided in the article. LEVEL OF EVIDENCE: Level I (therapeutic study = RCT).

Pulsed electromagnetic fields promote repair of focal articular cartilage defects with engineered osteochondral constructs.

Articular cartilage injuries are a common source of joint pain and dysfunction. We hypothesized that pulsed electromagnetic fields (PEMFs) would improve growth and healing of tissue-engineered cartilage grafts in a direction-dependent manner. PEMF stimulation of engineered cartilage constructs was first evaluated in vitro using passaged adult canine chondrocytes embedded in an agarose hydrogel scaffold. PEMF coils oriented parallel to the articular surface induced superior repair stiffness compared to both perpendicular PEMF (p = .026) and control (p = .012). This was correlated with increased glycosaminoglycan deposition in both parallel and perpendicular PEMF orientations compared to control (p = .010 and .028, respectively). Following in vitro optimization, the potential clinical translation of PEMF was evaluated in a preliminary in vivo preclinical adult canine model. Engineered osteochondral constructs (∅ 6 mm × 6 mm thick, devitalized bone base) were cultured to maturity and implanted into focal defects created in the stifle (knee) joint. To assess expedited early repair, animals were assessed after a 3-month recovery period, with microfracture repairs serving as an additional clinical control. In vivo, PEMF led to a greater likelihood of normal chondrocyte (odds ratio [OR]: 2.5, p = .051) and proteoglycan (OR: 5.0, p = .013) histological scores in engineered constructs. Interestingly, engineered constructs outperformed microfracture in clinical scoring, regardless of PEMF treatment (p < .05). Overall, the studies provided evidence that PEMF stimulation enhanced engineered cartilage growth and repair, demonstrating a potential low-cost, low-risk, noninvasive treatment modality for expediting early cartilage repair.

Pulsed Electromagnetic Field Stimulation of Bone Healing and Joint Preservation: Cellular Mechanisms of Skeletal Response.

The US FDA has approved pulsed electromagnetic fields (PEMFs) as a safe and effective treatment for nonunions of bone. Despite its clinical use, the mechanisms of action of electromagnetic stimulation of the skeleton have been elusive. Recently, cell membrane receptors have been identified as the site of action of PEMF and provide a mechanistic rationale for clinical use. This review highlights key processes in cell responses to PEMF as follows: (1) signal transduction through A2A and A3 adenosine cell membrane receptors and (2) dose-response effects on the synthesis of structural and signaling extracellular matrix (ECM) components. Through these actions, PEMF can increase the structural integrity of bone and cartilage ECM, enhancing repair, and alter the homeostatic balance of signaling cytokines, producing anti-inflammatory effects. PEMFs exert a proanabolic effect on the bone and cartilage matrix and a chondroprotective effect counteracting the catabolic effects of inflammation in the joint environment. Understanding of PEMF membrane targets, and of the specific intracellular pathways involved, culminating in the synthesis of ECM proteins and reduction in inflammatory cytokines, should enhance confidence in the clinical use of PEMF and the identification of clinical conditions likely to be affected by PEMF exposure.

Contribution of Circulatory Disturbances in Subchondral Bone to the Pathophysiology of Osteoarthritis.

PURPOSE OF REVIEW: This review describes the contributions of abnormal bone circulation to the pathophysiology of osteoarthritis. Combining dynamic imaging with MRI and PET with previous observations reveals that venous stasis and a venous outlet syndrome is most likely the key circulatory pathology associated with the initiation or progression of osteoarthritis. RECENT FINDINGS: MRI and PET have revealed that venous outflow obstruction results in physicochemical changes in subchondral bone to which osteoblasts are responsive. The osteoblasts express an altered pattern of cytokines, many of which can serve as structural or signaling molecules contributing to both bone remodeling and cartilage degeneration. The patterns of circulatory changes are associated with alterations in the physicochemical environment of subchondral bone, including hypoxia. Osteoblast cytokines can transit the subchondral bone plate and calcified cartilage and communicate with chondrocytes.

Effects of Chondroitinase ABC-Mediated Proteoglycan Digestion on Decellularization and Recellularization of Articular Cartilage.

Articular cartilage has a limited capacity to heal itself and thus focal defects often result in the development of osteoarthritis. Current cartilage tissue engineering strategies seek to regenerate injured tissue by creating scaffolds that aim to mimic the unique structure and composition of native articular cartilage. Decellularization is a novel strategy that aims to preserve the bioactive factors and 3D biophysical environment of the native extracellular matrix while removing potentially immunogenic factors. The purpose of this study was to develop a procedure that can enable decellularization and recellularization of intact articular cartilage matrix. Full-thickness porcine articular cartilage plugs were decellularized with a series of freeze-thaw cycles and 0.1% (w/v) sodium dodecyl sulfate detergent cycles. Chondroitinase ABC (ChABC) was applied before the detergent cycles to digest glycosaminoglycans in order to enhance donor chondrocyte removal and seeded cell migration. Porcine synovium-derived mesenchymal stem cells were seeded onto the decellularized cartilage scaffolds and cultured for up to 28 days. The optimized decellularization protocol removed 94% of native DNA per sample wet weight, while collagen content and alignment were preserved. Glycosaminoglycan depletion prior to the detergent cycles increased removal of nuclear material. Seeded cells infiltrated up to 100 µm into the cartilage deep zone after 28 days in culture. ChABC treatment enhances decellularization of the relatively dense, impermeable articular cartilage by reducing glycosaminoglycan content. ChABC treatment did not appear to affect cell migration during recellularization under static, in vitro culture, highlighting the need for more dynamic seeding methods.

Controversial role of arthroscopic meniscectomy of the knee: A review.

The role of arthroscopic partial meniscectomy (APM) in reducing pain and improving function in patients with meniscal tears remains controversial. Five recent high-quality randomized controlled trials (RCTs) compared non-operative management of meniscal tears to APM, with four showing no difference and one demonstrating superiority of APM. In this review, we examined the strengths and weaknesses of each of these RCTs, with particular attention to the occurrence of inadvertent biases. We also completed a quantitative analysis that compares treatment successes in each treatment arm, considering crossovers as treatment failures. Our analysis revealed that each study was an excellent attempt to compare APM with non-surgical treatment but suffered from selection, performance, detection, and/or transfer biases that reduce confidence in its conclusions. While the RCT remains the methodological gold standard for establishing treatment efficacy, the use of an RCT design does not in itself ensure internal or external validity. Furthermore, under our alternative analysis of treatment successes, two studies had significantly more treatment successes in the APM arm than the non-operative arm although original intention-to-treat analyses showed no difference between these two groups. Crossovers remain an important problem in surgical trials with no perfect analytical solution. With the studies available at present, no conclusion can be drawn concerning the optimal treatment modality for meniscal tears. Further work that minimizes significant biases and crossovers and incorporates sub-group and cost-benefit analyses may clarify therapeutic indications.