» Arthroscopic partial meniscectomy (APM) for the treatment of degenerative meniscal tears has been controversial, and quantification of its benefits has been limited by methodological problems and varying clinical definitions.» Among the problems with APM are patients crossing over from the treatment arm to which they have been randomized to another treatment and analyzed by the randomized treatment, whether they received that treatment or not.» Aggregated information suggests that a program of structured exercise is a reasonable initial treatment for degenerative meniscal tears with APM reserved for patients who fail nonsurgical therapy.

McCune–Albright Syndrome (MAS) is a rare mosaic disorder caused by somatic activating mutations of the GNAS gene, resulting in constitutive Gsα signaling and a broad spectrum of clinical phenotypes. The syndrome typically presents with fibrous dysplasia (FD) of bone, café-au-lait macules, and endocrinopathies such as gonadotropin-independent precocious puberty, hyperthyroidism, and/or growth hormone excess. FD, which characterizes the skeletal phenotype, results in the replacement of normal bone with disorganized fibro-osseous tissue, often leading to pain, deformities, and increased risk of fractures. This review discusses the following: 1. The molecular biology of the GNAS locus and its relation to the pathophysiology of FD/MAS; 2. The skeletal manifestations of FD/MAS; 3. Bone biomechanics and organizational skeletal aberrations observed in FD/MAS; and 4. Current and future therapeutic strategies for patients with FD/MAS. While there is much current literature available regarding FD/MAS, this review specifically aims to outline core understandings and summarize some of the latest investigations into the genotypic and phenotypic foundations of the disorders, while shedding new light on the biomechanical aberrations observed in skeletal structure within them and comparing them to those observed in related disease processes such as osteoporosis and Paget’s disease.

Pulsed Electromagnetic Fields (PEMF) are widely used, with excellent clinical outcomes. However, their mechanism of action has not yet been completely understood. The purpose of this review is to describe current observations on the mechanisms of PEMF, together with its clinical efficacy. Osteoblast responsiveness to PEMF is described on several scales, from the cell membrane to clinically relevant bone formation. PEMF has been shown to activate membrane adenosine receptors. The role of adenosine receptors in activating intracellular second messenger pathways, such as the canonical Wnt/β-catenin pathway and the mitogen-activated protein kinases (MAPK) pathway, is described. The responsiveness of osteoblasts and the synthesis of structural and signaling proteins constitute the role of PEMFs in promoting osteogenesis and bone matrix synthesis, and they are described. Multiple studies, ranging from observational and randomized to meta-analyses that investigate the clinical efficacy of PEMF, are described. This review presents a favorable conclusion on the clinical effects of PEMF while unlocking the “black box” of PEMF’s mechanism of action, thus improving confidence in the clinical utility of PEMF in bone repair.

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 degrees, 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 degrees 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 degrees 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.

Background Osteoarthritis (OA) is a widespread chronic joint disorder characterized by the degeneration of articular cartilage, extensive bone remodeling, ligamentous fibrosis, and synovial inflammation impacting millions. Shared factors like phenotypic similarities, hypofibrinolysis, and inflammation constitute similarities in pathophysiology and clinical manifestations between OA and peripheral vascular disease (PVD). This study investigated peripheral arterial flow characteristics, vascular wall thickness, and stiffness in knee OA to clarify a potential association with early atherosclerosis. Methods The OA cohort consisted of 35 knees with a mean age of 69 years. The control cohort consisted of 58 knees with a mean age of 68 years. Subjects underwent arterial ultrasound scanning of the common femoral, superficial femoral, and popliteal arteries. Data measured included peak systolic volumetric flow, intima-media thickness, systolic and diastolic vessel diameter, and simultaneous EKG and flow curves. Structural and functional vascular data were quantified using the incremental Young's modulus, pulse wave velocity (PWV), and distensibility. Results Significantly elevated arterial volumetric flow, measures of arterial stiffness, and intima-media wall thickness were observed in those with OA compared to those without. PWV as calculated by the Bramwell-Hill equation were found to be significantly greater in all three vessels of patients with OA. Conclusions This study supports the association between peripheral arterial pathology and knee OA, consistent with shared clinical and phenotypic traits. The observed characteristics of early vascular pathology suggest potential pathophysiologic linkages between OA and PVD. This foundational framework provides avenues for mechanistic studies exploring the relationship between these two disease processes.

Osteoarthritis (OA) is a prevalent, chronic joint disorder affecting millions of people worldwide, characterized by articular cartilage degradation, subchondral bone remodeling, synovial cytokine secretion, and osteophyte formation. OA primarily affects the hips, knees, hands, and spine. Patients with OA exhibit a higher prevalence of cardiovascular comorbidities and potentially important associations between OA and cardiovascular diseases have prompted investigations into potentially similar pathophysiological associations. This review explores the coexistence of atherosclerotic peripheral vascular disease (ASPVD) in OA patients, including evidence from a contemporary study suggesting associations between OA and arterial wall thickness and blood flow changes which are characteristic of early atherosclerosis, and which stimulate reactive pathology in endothelial cells. Observations from this study demonstrate elevated arterial flow volume and increased intima-media thickness in arteries ipsilateral to OA knees, suggesting a potential link between OA and arterial wall disease. We further explore the intricate relationship between the vascular system and skeletal health, highlighting bidirectional interactions among endothelial cells, inflammatory cells, and various bone cells. Mechanical endothelial cell dysfunction is discussed, emphasizing the impact of vessel wall material changes and endothelial cell responses to alterations in fluid shear stress. Inflammatory changes in OA and ASPVD are also explored, showcasing shared pathophysiological processes involving immune cell infiltration and pro-inflammatory cytokines. Additionally, the role of hypofibrinolysis in OA and ASPVD is discussed, highlighting similarities in elevations of the hypercoagulative and hypofibrinolytic factor, plasminogen activator inhibitor (PAI-1). The review suggests a provocative relationship among low-grade chronic inflammation, endothelial dysfunction, and hypofibrinolytic states in OA and ASPVD, warranting further investigation. In conclusion, this review provides an exploration of the possible associations between OA and ASPVD. While the ongoing study’s findings and other reports are observational, they suggest shared pathophysiological processes and emphasize the need for further research to elucidate additional potentially correlative linkages between these conditions. Understanding common molecular pathways may pave a way for targeted interventions that address both OA and ASPVD.

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.

Background Total knee arthroplasties (TKAs) exhibit an 8 to 30% risk of suboptimal outcomes, resulting in persistent symptoms, individual morbidity, and revision surgery, prompting a contemporary focus on risk reduction and outcome improvement. This study introduces hierarchical cluster analysis as a way of preoperatively assessing the likelihood of success/failure of TKA based on several patient-reported outcome measures (PROMs), which have been analyzed both intact and with component questions as individual variables. Methods The study utilized data on 1,433 TKAs from The Miriam Hospital's Function and Outcomes Research for Comparative Effectiveness in Total Joint Replacement registry. Outcomes are expressed as Knee Injury and Osteoarthritis Outcome Score pain and function scores. Criteria for success/failure were developed with an integrative, anchor-based, minimum clinically important difference. Preoperative and postoperative PROMs were studied by cluster analysis. Results There were three sequential cluster analyses that revealed clusters of patients, based upon preoperative patient responses that were predictive of surgical outcomes. Clusters varied most significantly in their responses to individual component questions of preoperative PROMs. Extracting and combining the clinically meaningful patient-reported component questions yielded a new, and clinically relevant, outcome measure that has the potential to preoperatively predict postoperative outcomes of TKA. Conclusions In contrast to a single medical, psychological, or social variable, cluster analysis offers the opportunity to develop a whole-patient profile that reflects the contextual interactions of sociodemographic and clinical variables in predicting outcomes. In the context of determining clinical meaningfulness, cluster analysis has one of its major strengths.

Bone marrow edema (BME), also termed bone marrow lesions, is a syndrome characterized by bone pain and the appearance of high signal intensity on T2 fat-suppressed and short tau inversion recovery (STIR) MRI sequences. BME can be related to trauma or a variety of non-traumatic diseases, and current treatment modalities include non-steroidal anti-inflammatory drugs (NSAIDS), bisphosphonates, denosumab, extracorporeal shockwave therapy (ESWT), the vasoactive prostacyclin analogue iloprost, and surgical decompression. Spontaneous BME is a subset that has been observed with no apparent causative conditions. It is most likely caused by venous outflow obstruction and intraosseous hypertension. These are mechanistically related to impaired perfusion and ischemia in several models of BME and are related to bone remodeling. The association of perfusion abnormalities and bone pain provides the pathophysiological rationale for surgical decompression. We present a case of spontaneous BME and a second case of spontaneous migratory BME treated with surgical decompression and demonstrate resolution of pain and the high signal intensity on MRI. This report provides an integration of the clinical syndrome, MR imaging characteristics, circulatory pathophysiology, and treatment. It draws upon several studies to suggest that both the bone pain and the MRI characteristics are related to venous stasis, and when circulatory pathologies are relieved by decompression or fenestration, both the bone pain and the MRI signal abnormalities resolve.

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.

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.

Understanding global body balance can optimize the postoperative course for patients undergoing spinal or lower limb surgical realignment. This observational cohort study aimed to characterize patients with reported imbalance and identify predictors. The CDC establishes a representative sample annually via the NHANES. All participants who said "yes" (Imbalanced) or "no" (Balanced) to the following question were identified from 1999-2004: "During the past 12 months, have you had dizziness, difficulty with balance or difficulty with falling?" Univariate analyses compared Imbalanced versus Balanced subjects and binary logistic regression modeling predicted for Imbalance. Of 9964 patients, imbalanced (26.5%) were older (65.4 vs. 60.6 years), with more females (60% vs. 48%). Imbalanced subjects reported higher rates of comorbidities, including osteoporosis (14.4% vs. 6.6%), arthritis (51.6% vs. 31.9%), and low back pain (54.4% vs 32.7%). Imbalanced patients had more difficulty with activities, including climbing 10 steps (43.8% vs. 21%) and stooping/crouching/kneeling (74.3% vs. 44.7%), and they needed greater time to walk 20 feet (9.5 vs. 7.1 s). Imbalanced subjects had significantly lower caloric and dietary intake. Regression revealed that difficulties using fingers to grasp small objects (OR: 1.73), female gender (OR: 1.43), difficulties with prolonged standing (OR: 1.29), difficulties stooping/crouching/kneeling (OR: 1.28), and increased time to walk 20 feet (OR: 1.06) were independent predictors of Imbalance (all p < 0.05). Imbalanced patients were found to have identifiable comorbidities and were detectable using simple functional assessments. Structured tests that assess dynamic functional status may be useful for preoperative optimization and risk-stratification for patients undergoing spinal or lower limb surgical realignment.

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.

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.

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.

Familial exudative vitreoretinopathy (FEVR) is a genetic disorder whose presentation can include osteoporosis, multiple fractures, and incomplete retinal angiogenesis leading to retinal detachment and blindness if left untreated. Discussed herein are the cases of two pediatric siblings who presented to the orthopedic service with multiple fractures and, through interdisciplinary management, were diagnosed with FEVR and treated appropriately before permanent visual impairment. The skeletal manifestations of FEVR, which have not been explored in depth in prior literature, are described. One sibling presented to orthopedic services for evaluation of a closed distal radius fracture sustained while playing sports. A comprehensive history revealed he had suffered at least four appendicular fractures in his lifetime, and dual-energy x-ray absorptiometry (DEXA) scan revealed his bone density to be in the first percentile for his age. Concurrent evaluation of his younger sibling revealed a similar history of multiple fractures and low bone density. Referral to genetic services and ensuing whole-exome sequencing revealed a likely pathogenic variant in both siblings' LRP5 gene, the only known causative mutation for FEVR that leads to skeletal manifestations. While FEVR is well known in genetic and ophthalmologic settings, greater awareness of FEVR and other genetic disorders that predispose to fractures in pediatric populations is warranted in orthopedic settings. This will lead to reduced sequelae in pediatric patients with genetic disorders and improved interdisciplinary expertise. The story of these siblings illustrates that a high index of suspicion for genetic diseases is essential when treating children with osteoporosis and growth delays.

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–β-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.

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.

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.