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An introduction is presented in which the editor discusses various articles within the issue on topics including sports medicine, exercise induced rhabdomyolysis, and post-traumatic osteoarthritis after anterior cruciate ligament injury.

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 ho-meostatic disturbances represent a not insignificant portion of fracture patients seen in a fracture liaison service. [ABSTRACT FROM AUTHOR]

Osteomalacia is defined by the undermineralization of newly formed bone due to a lack of available calcium, phosphorus, or vitamin D. Causative factors of osteomalacia include nutritional deficiency, diminished absorptive capabilities (often due to gastrointestinal disorders), and renal insufficiency. Renal osteodystrophy is a specific form of metabolic bone disease defined by the presence of osteomalacia and associated hyperparathy-roidism secondary to a malfunction in, or absence of, renal parenchyma. This reduces the conversion of vitamin D to its active form, thus leading to a cascade of effects that negatively impact the stability of the skeleton. Os-teomalacia occurs across a spectrum of severity and can produce severe consequences for specific populations, including patients with dietary, nutritional, and absorptive deficiencies. Renal osteodystrophy affects patients with chronic kidney disease, those undergoing dialysis, and renal transplant patients. Special considerations must be taken into account when assessing the bone health of patients fitting these criteria. [ABSTRACT FROM AUTHOR]

The roles of a fracture liaison service (FLS) are extensive and include, but are not limited to: 1) providing a standardized framework for the evaluation and management of low-energy fractures, also known as fragility fractures; 2) improving patient outcomes through the recognition of fragility fractures as signal events requiring further diagnostic explanation; and 3) lowering direct and indirect healthcare expenditures. One of the central tenets of the FLS is its recognition of fragility fractures as warning signs of underlying pathology, often osteoporosis or other metabolic bone diseases. This understanding, combined with the application of a multidisciplinary management team specialized in diagnosing and treating such pathologies, allows for better short- and long-term management of patients and concordant improvement in outcomes. This article should be viewed as a thematic introduction to the FLS, with others in this volume each illustrating specific examples of how FLS paradigms facilitate the roles described herein. [ABSTRACT FROM AUTHOR]

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, 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 (FORCE-TJR) registry. Outcomes are expressed as Knee Injury and Osteoarthritis Outcome Score (KOOS) pain and function scores. Criteria for success/failure were developed with an integrative, anchor-based, minimum clinically important difference. Preoperative and postoperative patient-reported outcome measures (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 total knee arthroplasty., Conclusion: 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., (Copyright © 2024 Elsevier Inc. All rights reserved.)

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., (© 2024 The Author(s). Published by IMR Press.)

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., Competing Interests: The authors declare no conflict of interest. Given the role as Guest Editor, Roy K. Aaron had no involvement in the peer-review of this article and has no access to information regarding its peer-review. Full responsibility for the editorial process for this article was delegated to Emerito Carlos Rodriguez-Merchan., (© 2024 The Author(s). Published by IMR Press.)

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.

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., Competing Interests: B.G.D. reports disclosure as follows: SpineVision, paid consultant. P.G.P. reports disclosures as follows: Allosource, financial or material support; Cervical Scoliosis Research Society, research support; Globus Medical, paid presenter and speaker; Medtronic, paid consultant; Royal Biologics, paid consultant; Spine, editorial or governing board; Spinewave, paid consultant; Terumo, paid consultant; Zimmer, paid presenter or speaker. R.K.A. reports disclosures as follows: AAOS, board or committee member. A.D. reports disclosures as follows: EOS, paid consultant; Orthofix, Inc., paid consultant, research support; SpineArt, paid consultant; Medtronic/Medicrea, paid consultant; Springer: publishing royalties, financial or material support; Stryker: paid consultant, all outside submitted work. C.B.P. reports disclosures as follows: DePuy, A Johnson & Johnson Company Ethicon, paid presenter or speaker. Virginie Lafage reports disclosures as follows: Alphatec Spine, paid consultant; DePuy, A Johnson & Johnson Company, paid presenter and speaker; European Spine Journal, editorial or governing board; Globus Medical, paid consultant; International Spine Study Group, board or committee member; Nuvasive, IP royalties; Scoliosis Research Society, board or committee member; Stryker, paid presenter or speaker. The remaining authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

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.

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., Competing Interests: Financial disclosure statements have been obtained, and no conflicts of interest have been reported by the authors or by any individuals in control of the content of this article., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

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., Competing Interests: Financial disclosure statements have been obtained, and no conflicts of interest have been reported by the authors or by any individuals in control of the content of this article., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

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., Competing Interests: Financial disclosure statements have been obtained, and no conflicts of interest have been reported by the authors or by any individuals in control of the content of this article., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

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)., (Copyright © 2021 by the American Academy of Orthopaedic Surgeons.)

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.

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.

Osteonecrosis, also known as avascular necrosis or AVN, is characterized by a stereotypical pattern of cell death and a complex repair process of bone resorption and formation. It is not the necrosis itself but rather the resorptive component of the repair process that results in loss of structural integrity and subchondral fracture. Most likely, a common pathophysiological pathway exists involving compromised subchondral microcirculation. Decreased femoral head blood flow can occur through three mechanisms: vascular interruption by fractures or dislocation, intravascular occlusion from thrombi or embolic fat, or intraosseous extravascular compression from lipocyte hypertrophy or Gaucher cells. In this review, we emphasize etiologic relationships derived mostly from longitudinal cohort studies or meta-analyses whose causal relationships to osteonecrosis can be estimated with confidence. Understanding risk factors and pathophysiology has therapeutic implications since several treatment regimens are available to optimize femoral head circulation, interrupt bone resorption, and preserve the subchondral bone.

This study characterizes changes in subchondral bone circulation in OA and examines relationships to bone structure and cartilage degeneration in Dunkin-Hartley guinea pigs. We have used dynamic contrast-enhanced MRI (DCE-MRI) and PET, with pharmacokinetic modeling, to characterize subchondral bone perfusion. Assessments are made of perfusion kinetics and vascular permeability by MRI, and blood volume and flow, and radionuclide incorporation into bone, by PET. These parameters are compared to cartilage lesion severity and bone histomorphometry. Assessments of intraosseous thrombi are made morphologically. Prolonged signal enhancement during the clearance phase of MRI correlated with OA severity and suggested venous stasis. Vascular permeability was not increased indicating that transvascular migration of contrast agent was not responsible for signal enhancement. Intraosseous thrombi were not observed. Decreased perfusion associated with severe OA was confirmed by PET and was associated with reduced radionuclide incorporation and osteoporosis. MRI and PET can be used to characterize kinetic parameters of circulation in OA and correlate them with subchondral bone metabolism of interest to the pathophysiology of OA. The significance of these observations may lie in alterations induced in the expression of cytokines by OA osteoblasts that are related to bone remodeling and cartilage breakdown., (© 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.)

Fractal patterns characterize healthy biological systems and are considered to reflect the ability of the system to adapt to varying environmental conditions. Previous research has shown that fractal patterns in gait are altered following natural aging or disease, and this has potential negative consequences for gait adaptability that can lead to increased risk of injury. However, the flexibility of a healthy neurological system to exhibit different fractal patterns in gait has yet to be explored, and this is a necessary step toward understanding human locomotor control. Fifteen participants walked for 15min on a treadmill, either in the absence of a visual stimulus or while they attempted to couple the timing of their gait with a visual metronome that exhibited a persistent fractal pattern (contained long-range correlations) or a random pattern (contained no long-range correlations). The stride-to-stride intervals of the participants were recorded via analog foot pressure switches and submitted to detrended fluctuation analysis (DFA) to determine if the fractal patterns during the visual metronome conditions differed from the baseline (no metronome) condition. DFA α in the baseline condition was 0.77±0.09. The fractal patterns in the stride-to-stride intervals were significantly altered when walking to the fractal metronome (DFA α=0.87±0.06) and to the random metronome (DFA α=0.61±0.10) (both p<.05 when compared to the baseline condition), indicating that a global change in gait dynamics was observed. A variety of strategies were identified at the local level with a cross-correlation analysis, indicating that local behavior did not account for the consistent global changes. Collectively, the results show that a gait dynamics can be shifted in a prescribed manner using a visual stimulus and the shift appears to be a global phenomenon., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Osteoarthritis (OA) is a disease of high prevalence that produces substantial morbidity and is a leading cause of physical and psychological disability and expense, including time lost from work, medical care, and disability support. Until recently, the focus of research into the pathophysiology of OA has been on articular cartilage and has not resulted in either biomarkers of OA activity or effective targets for disease-modifying therapy. The contemporary paradigm of OA considers involvement of all joint tissues. It has been shown that, in later-stage OA, bone blood flow and oxygen content are markedly reduced and have a deleterious effect on bone cells, inducing them to release proteins (cytokines) that contribute to the bone remodeling and cartilage breakdown seen in OA.

A major problem with transcutaneous osseointegrated implants is infection, mainly due to improper closure of the implant-skin interface. Therefore, the design of transcutaneous osseointegrated devices that better promote skin growth around these exit sites needs to be examined and, if successful, would clearly limit infection. Due to the success already demonstrated for orthopedic implants, developing surfaces with biologically inspired nanometer features is a design criterion that needs to be investigated for transcutaneous devices. This study therefore examined the influence of nanotextured titanium (Ti) created through electron beam evaporation and anodization on keratinocyte (skin-forming cell) function. Electron beam evaporation created Ti surfaces with nanometer features while anodization created Ti surfaces with nanotubes. Conventional Ti surfaces were largely micron rough, with few nanometer surface features. Results revealed increased keratinocyte adhesion in addition to increased keratinocyte spreading and differences in keratinocyte filopodia extension on the nanotextured Ti surfaces prepared by either electron beam evaporation or anodization compared to their conventional, unmodified counterparts after 4h. Results further revealed increased keratinocyte proliferation and cell spreading over 3 and 5days only on the nanorough Ti surfaces prepared by electron beam evaporation compared to both the anodized nanotubular and unmodified Ti surfaces. Therefore, the results from this in vitro study provided the first evidence that nano-modification techniques should be further researched as a means to possibly improve skin growth, thereby improving transcutaneous osseointegrated orthopedic implant longevity., (Copyright 2009 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Osteoarthritis and avascular necrosis are common clinical entities with unknown origins. Recently, vascular changes were implicated in the pathogenesis of both conditions. This article discusses the use of novel noninvasive imaging techniques as a means of assessing bone perfusion and quantifying differences seen in osteoarthritis and avascular necrosis. Review of our human data suggests that the MRI contrast dye is retained for longer periods of time, suggesting decreased perfusion out of regions of osteoarthritis and avascular necrosis. Use of such a noninvasive measure of assessing bone perfusion could be useful in the diagnosis, prevention, and treatment of not only osteoarthritis and avascular necrosis but also other entities that affect the musculoskeletal system.

Musculoskeletal injury is the most common type of injury among survivors of combat trauma, and combat-related trauma is challenging for an orthopaedic surgeon to treat. Methods of treatment are evolving, but significant gaps remain as knowledge of civilian trauma is extrapolated to combat trauma.

Musculoskeletal war wounds often involve massive injury to bone and soft tissue that differ markedly in character and extent compared with most injuries seen in civilian practice. These complex injuries have challenged orthopaedic surgeons to the limits of their treatment abilities on the battlefield, during medical evacuation, and in subsequent definitive or reconstructive treatment. Newer methodologies are being used in the treatment of these wounds to prevent so-called second hit complications, decrease complications associated with prolonged medical evacuation, reduce the incidence of infection, and restore optimal function. Basic science advances hold the promise of providing foundations for future treatment options that may improve both bone and soft-tissue healing. Research on the treatment of these often devastating wounds also will have broad applicability to trauma resulting from acts of terrorism or from natural disasters.

In vitro cartilage tissue engineering culture systems benefit from a fine balance of biochemical and mechanical components to maintain the chondrocyte phenotype. This balance, however, can be disrupted by using typical methods for cultivating chondrogenic cells in medium supplemented with fetal bovine serum (FBS) and growth factors. Our goal was to determine the effects of fluid-dynamic stimuli, fetal bovine serum and dexamethasone on the chondrogenesis of 14-day synoviocyte pellet cultures in the presence of TGF-beta1. We employed a pellet culture system that provides a highly cellular three-dimensional structure that permits differentiation and extracellular matrix synthesis. Our results indicated that FBS inhibited glycosaminoglycan (GAG) and type II collagen production. Interestingly, the effect of dynamic stimuli was modulated by the presence of FBS; mixed serum-free cultures had increased GAG production, whereas mixed cultures with 10% FBS exhibited less GAG production compared with their static counterparts, possibly due to pronounced suppressive effects of FBS via increased transport. Dexamethasone addition during the first week of culture resulted in enhanced extracellular matrix production and increased cellularity. Moreover, the presence of 10% FBS in addition to ITS(+) and TGF-beta1 did not significantly increase cell proliferation compared with serum-free medium. These results indicate the importance of a comprehensive analysis of growth conditions for each cell culture system.