Impact of Induced Pluripotent Stem Cells in Bone Repair and Regeneration
AbstractPurpose of ReviewThe main objective of this article is to investigate the current trends in the use of induced pluripotent stem cells (iPSCs) for bone tissue repair and regeneration.Recent FindingsPluripotent stem cell –based tissue engineering has extended innovative therapeutic approaches for regenerative medicine. iPSCs have shown osteogenic differentiation capabilities and would be an innovative resource of stem cells for bone tissue regenerative applications.SummaryThis review recapitulates the current knowledge and recent progress regarding utilization of iPSCs for bone therapy. A review of current find...
Source: Current Osteoporosis Reports - June 29, 2019 Category: Orthopaedics Source Type: research

Integrins in Osteocyte Biology and Mechanotransduction
AbstractPurpose of ReviewOsteocytes are the main mechanosensitive cells in bone. Integrin-based adhesions have been shown to facilitate mechanotransduction, and therefore play an important role in load-induced bone formation. This review outlines the role of integrins in osteocyte function (cell adhesion, signalling, and mechanotransduction) and possible role in disease.Recent FindingsBoth β1 and β3 integrins subunits have been shown to be required for osteocyte mechanotransduction. Antagonism of these integrin subunits in osteocytes resulted in impaired responses to fluid shear stress. Various disease states (os...
Source: Current Osteoporosis Reports - June 27, 2019 Category: Orthopaedics Source Type: research

Studies on Osteocytes in Their 3D Native Matrix Versus 2D In Vitro Models
AbstractPurpose of ReviewOsteocytes are responsible for mechanosensing and mechanotransduction in bone and play a crucial role in bone homeostasis. They are embedded in a calcified collagenous matrix and connected with each other through the lacuno-canalicular network. Due to this specific native environment, it is a challenge to isolate primary osteocytes without losing their specific characteristics in vitro. This review summarizes the commonly used and recently established models to study the function of osteocytes in vitro.Recent FindingsOsteocytes are mostly studied in monolayer culture, but recently, 3D models of ost...
Source: Current Osteoporosis Reports - June 25, 2019 Category: Orthopaedics Source Type: research

Investigating Osteocytic Perilacunar/Canalicular Remodeling
AbstractPurpose of ReviewIn perilacunar/canalicular remodeling (PLR), osteocytes dynamically resorb, and then replace, the organic and mineral components of the pericellular extracellular matrix. Given the enormous surface area of the osteocyte lacuna-canalicular network (LCN), PLR is important for maintaining homeostasis of the skeleton. The goal of this review is to examine the motivations and critical considerations for the analysis of PLR, in both in vitro and in vivo systems.Recent FindingsMorphological approaches alone are insufficient to elucidate the complex mechanisms regulating PLR in the healthy skeleton and in ...
Source: Current Osteoporosis Reports - June 22, 2019 Category: Orthopaedics Source Type: research

CaMKK2 Signaling in Metabolism and Skeletal Disease: a New Axis with Therapeutic Potential
AbstractPurpose of ReviewAge and metabolic disorders result in the accumulation of advanced glycation endproducts (AGEs), oxidative stress, and inflammation, which cumulatively cause a decline in skeletal health. Bone becomes increasingly vulnerable to fractures and its regenerative capacity diminishes under such conditions. With a rapidly aging population in the USA and the global increase in diabetes, efficacious, multi-dimensional therapies that can treat or prevent skeletal diseases associated with metabolic dysfunction and inflammatory disorders are acutely needed.Recent FindingsCa2+/calmodulin-dependent protein kinas...
Source: Current Osteoporosis Reports - May 21, 2019 Category: Orthopaedics Source Type: research

Towards a Connectomic Description of the Osteocyte Lacunocanalicular Network in Bone
AbstractPurpose of ReviewOsteocytes are the most abundant bone cells. They are completely encased in mineralized tissue, sitting inside lacunae that are connected by a multitude of canaliculi. In recent years, the osteocyte network has been shown to fulfill endocrine functions and to communicate with a number of other organs. This review addresses emerging knowledge on the connectome of the lacunocanalicular network in different types of bone tissue.Recent FindingsRecent advances in three-dimensional imaging technology started to reveal parameters that are well known from general theory to characterize the function of netw...
Source: Current Osteoporosis Reports - May 15, 2019 Category: Orthopaedics Source Type: research

RNA-seq in Skeletal Biology
AbstractPurpose of ReviewThe goal of this paper is to review state-of-the-art transcriptome profiling methods and their recent applications in the field of skeletal biology.Recent FindingsNext-generation sequencing of mRNA (RNA-seq) methods have been established and routinely used in skeletal biology research. RNA-seq has led to the identification of novel genes and transcription factors involved in skeletal development and disease, through its application in small and large animal models, as well as human tissue and cells. With the availability of advanced techniques such as single-cell RNA-seq, novel cell types in skelet...
Source: Current Osteoporosis Reports - May 15, 2019 Category: Orthopaedics Source Type: research

Contextual Regulation of Skeletal Physiology by Notch Signaling
This article reviews the past 2  years of research on Notch signaling as it relates to bone physiology, with the goal of reconciling seemingly discrepant findings and identifying fruitful areas of potential future research.Recent FindingsConditional animal models and high-throughput omics have contributed to a greater understanding of the context-dependent role of Notch signaling in bone. However, significant gaps remain in our understanding of how spatiotemporal context and epigenetic state dictate downstream Notch phenotypes.SummaryBiphasic activation of Notch signaling orchestrates progression of mesenchymal progen...
Source: Current Osteoporosis Reports - May 8, 2019 Category: Orthopaedics Source Type: research

Nuclear Fibroblast Growth Factor Receptor Signaling in Skeletal Development and Disease
AbstractPurpose of ReviewFibroblast growth factor receptor (FGFR) signaling regulates proliferation and differentiation during development and homeostasis. While membrane-bound FGFRs play a central role in these processes, the function of nuclear FGFRs is also critical. Here, we highlight mechanisms for nuclear FGFR translocation and the effects of nuclear FGFRs on skeletal development and disease.Recent FindingsFull-length FGFRs, internalized by endocytosis, enter the nucleus through β-importin-dependent mechanisms that recognize the nuclear localization signal within FGFs. Alternatively, soluble FGFR intracellular f...
Source: Current Osteoporosis Reports - April 13, 2019 Category: Orthopaedics Source Type: research

Inter-site Variability of the Human Osteocyte Lacunar Network: Implications for Bone Quality
This article provides a review on the variability of the osteocyte lacunar network in the human skeleton. It highlights characteristics of the osteocyte lacunar network in relation to different skeletal sites and fracture susceptibility.Recent FindingsApplication of 2D analyses (quantitative backscattered electron microscopy, histology, confocal laser scanning microscopy) and 3D reconstructions (microcomputed tomography and synchrotron radiation microcomputed tomography) provides extended high-resolution information on osteocyte lacunar properties in individuals of various age (fetal, children ’s growth, elderly), se...
Source: Current Osteoporosis Reports - April 12, 2019 Category: Orthopaedics Source Type: research

A Second Career for Chondrocytes — Transformation into Osteoblasts
AbstractPurpose of ReviewThe goal of the review is to summarize the current knowledge on the process of chondrocyte-to-osteoblast transdifferentiation during endochondral bone formation and its potential implications in fracture healing and disease.Recent FindingsLineage tracing experiments confirmed the transdifferentiation of chondrocytes into osteoblasts. More recent studies lead to the discovery of molecules involved in this process, as well as to the hypothesis that these cells may re-enter a stem cell-like phase prior to their osteoblastic differentiation.SummaryThis review recapitulates the current knowledge regardi...
Source: Current Osteoporosis Reports - April 4, 2019 Category: Orthopaedics Source Type: research

The Osteocyte as a Novel Key Player in Understanding Periodontitis Through its Expression of RANKL and Sclerostin: a Review
AbstractPurpose of ReviewPeriodontitis is the inflammation-associated bone loss disease of the alveolar bone that surrounds teeth. Classically, the emphasis on the etiology of periodontitis has been on the products of periodontal pathogens that lead to an inflammatory response of thesoft tissues of the periodontium, eventually leading to activation of osteoclasts that degrade the alveolar bone. Until recently, the response of osteocytes that populate the alveolar bone, and that are known for their regulatory role in bone anabolism and catabolism, has not been addressed.Recent FindingsThis review demonstrates that osteocyte...
Source: Current Osteoporosis Reports - March 28, 2019 Category: Orthopaedics Source Type: research

Pro-inflammatory Cytokines and Osteocytes
AbstractPurpose of ReviewAn elevated level of pro-inflammatory cytokines in inflammatory conditions causes bone loss and disrupts vital organ function. Osteocytes comprise>  95% of the cellular component in bone tissue, produce a range of cytokines and signaling molecules, and influence bone and other organ function. In this review, we hypothesized that an elevated level of pro-inflammatory cytokines in inflammatory conditions affects osteocyte survival and function thereby possibly amplifying inflammation, and causing bone loss and non-bone clinical complications.Recent FindingsSeveral studies have reported that...
Source: Current Osteoporosis Reports - March 26, 2019 Category: Orthopaedics Source Type: research

Falls and Fractures in Diabetes —More than Bone Fragility
AbstractPurpose of ReviewBased on a systematic literature search, we performed a comprehensive review of risk factors for falls and fractures in patients with diabetes.Recent FindingsPatients with diabetes have an increased risk of fractures partly explained by increased bone fragility. Several risk factors as altered body composition including sarcopenia and obesity, impaired postural control, gait deficits, neuropathy, cardiovascular disease, and other co-morbidities are considered to increase the risk of falling.SummaryDiabetes and bone fragility is well studied, but new thresholds for fracture assessment should be cons...
Source: Current Osteoporosis Reports - March 26, 2019 Category: Orthopaedics Source Type: research

MicroRNAs in Bone Metastasis
AbstractPurpose of ReviewThis review provides an update on the recent literature describing the role of microRNAs (miRNAs) in cancer formation and bone metastasis. We confined our focus on osteosarcoma, breast cancer, prostate cancer, and epithelial-mesenchymal transition.Recent FindingsIn all areas covered, major discoveries on the role of miRNAs in tumorigenesis and metastasis have been made. Novel signaling networks were identified with miRNAs having a central function. Potential improvements in the diagnosis of malignant diseases and the long-term follow-up might become possible by the use of miRNAs. Furthermore, miRNA...
Source: Current Osteoporosis Reports - March 23, 2019 Category: Orthopaedics Source Type: research

Wnt Antagonists in Hematopoietic and Immune Cell Fate: Implications for Osteoporosis Therapies
AbstractPurpose of ReviewWe reviewed the current literature on the roles of the Wnt antagonists sclerostin (Sost) and sclerostin-containing domain protein 1 (Sostdc1) on bone homeostasis, the relationship of the hypoxia-inducible factor (Hif) and von Hippel-Lindau (Vhl) pathways on Sost expression, and how changes in bone induced by depletion ofSost, Sostdc1, andVhl affect hematopoietic cells.Recent FindingsB cell development is adversely affected in Sost-knockout mice and is more severely affected inVhl-knockout mice. Inflammation in theSost−/− bone microenvironment could alter hematopoietic stem cell behavior...
Source: Current Osteoporosis Reports - March 5, 2019 Category: Orthopaedics Source Type: research

The Emerging Role of Glucose Metabolism in Cartilage Development
AbstractPurpose of ReviewProper cartilage development is critical to bone formation during endochondral ossification. This review highlights the current understanding of various aspects of glucose metabolism in chondrocytes during cartilage development.Recent FindingsRecent studies indicate that chondrocytes transdifferentiate into osteoblasts and bone marrow stromal cells during endochondral ossification. In cartilage development, signaling molecules, including IGF2 and BMP2, tightly control glucose uptake and utilization in a stage-specific manner. Perturbation of glucose metabolism alters the course of chondrocyte matur...
Source: Current Osteoporosis Reports - March 4, 2019 Category: Orthopaedics Source Type: research

Genetics of Bone and Muscle Interactions in Humans
AbstractPurpose of ReviewTo summarize the evidence from recent studies on the shared genetics between bone and muscle in humans.Recent FindingsGenome-wide association studies (GWAS) have successfully identified a multitude of loci influencing the variability of different bone or muscle parameters, with multiple loci overlapping between the traits. In addition, joint analyses of multiple correlated musculoskeletal traits (i.e., multivariate GWAS) have underscored several genes with possible pleiotropic effects on both bone and muscle includingMEF2C andSREBF1. Notably, several of the proposed pleiotropic genes have been vali...
Source: Current Osteoporosis Reports - February 28, 2019 Category: Orthopaedics Source Type: research

Targeting Cell Senescence for the Treatment of Age-Related Bone Loss
AbstractPurpose of ReviewWe review cell senescence in the context of age-related bone loss by broadly discussing aging mechanisms in bone, currently known inducers and markers of senescence, the senescence-associated secretory phenotype (SASP), and the emerging roles of senescence in bone homeostasis and pathology.Recent FindingsCellular senescence is a state of irreversible cell cycle arrest induced by insults or stressors including telomere attrition, oxidative stress, DNA damage, oncogene activation, and other intrinsic or extrinsic triggers and there is mounting evidence for the role of senescence in aging bone. Cellul...
Source: Current Osteoporosis Reports - February 26, 2019 Category: Orthopaedics Source Type: research

Hypoxia Signaling in the Skeleton: Implications for Bone Health
AbstractPurpose of ReviewWe reviewed recent literature on oxygen sensing in osteogenic cells and its contribution to development of a skeletal phenotype, the coupling of osteogenesis with angiogenesis and integration of hypoxia into canonical Wnt signaling, and opportunities to manipulate oxygen sensing to promote skeletal repair.Recent FindingsOxygen sensing in osteocytes can confer a high bone mass phenotype in murine models; common and unique targets of HIF-1 α and HIF-2α and lineage-specific deletion of oxygen sensing machinery suggest differentia utilization and requirement of HIF-α proteins in the d...
Source: Current Osteoporosis Reports - February 6, 2019 Category: Orthopaedics Source Type: research

RAGE Signaling in Skeletal Biology
The objective of the current review is to describe the literature over RAGE signaling in skeletal biology as well as discuss the clinical potential of RAGE as a diagnostic and/or therapeutic target in bone disease.Recent FindingsThe role of RAGE and its ligands during skeletal homeostasis, tissue repair, and disease onset/progression is beginning to be uncovered. For example, detrimental effects of the RAGE ligands, advanced glycation end products (AGEs), have been identified for osteoblast viability/activity, while others have observed that low level AGE exposure stimulates osteoblast autophagy, which subsequently promote...
Source: Current Osteoporosis Reports - January 26, 2019 Category: Orthopaedics Source Type: research

Glucocorticoid-Induced Osteoporosis: New Insights into the Pathophysiology and Treatments
AbstractPurpose of this ReviewThe goal of the review is to provide an updated understanding of the pathophysiology of glucocorticoid-induced osteoporosis and treatment recommendations.Recent FindingsGlucocorticoids reduce osteoblast and osteocyte lifespan and activity and reduce the vascularity of the bone that together may explain the greater reductions in bone strength than those of bone mass. Treatments with parathyroid hormone fragments appear to reverse glucocorticoid-induced bone loss and fracture risk partially through maintaining bone vascularity and bone strength.SummaryThis review identifies how glucocorticoid an...
Source: Current Osteoporosis Reports - January 26, 2019 Category: Orthopaedics Source Type: research

Mechanisms Underlying Normal Fracture Healing and Risk Factors for Delayed Healing
AbstractPurpose of ReviewSubstantial advances have been made in understanding the biological basis of fracture healing. Yet, it is unclear whether the presence of osteoporosis or prior or current osteoporosis therapy influences the healing process or is associated with impaired healing. This review discusses the normal process of fracture healing and the role of osteoporosis and patient-specific factors in relation to fracture repair.Recent FindingsThe definitive association of osteoporosis to impaired fracture healing remains inconclusive because of limited evidence addressing this point. eStudies testing anabolic agents ...
Source: Current Osteoporosis Reports - January 22, 2019 Category: Orthopaedics Source Type: research

Stopping Denosumab
AbstractPurpose of ReviewDenosumab discontinuation is associated with a rebound effect manifesting by an increased risk of multiple spontaneous vertebral fractures. The purpose of this review is to (1) better characterize this risk and (2) find solutions to avoid it.Recent FindingsIn the absence of a potent bisphosphonate prescription at denosumab discontinuation, the frequency of multiple vertebral fractures is common or frequent ( ≥ 1/100 and
Source: Current Osteoporosis Reports - January 18, 2019 Category: Orthopaedics Source Type: research

In Vivo Osteocyte Mechanotransduction: Recent Developments and Future Directions
AbstractPurpose of ReviewMechanical loading is an essential stimulus for skeletal tissues. Osteocytes are primarily responsible for sensing mechanical stimuli in bone and for orchestrating subsequent responses. This is critical for maintaining homeostasis, and responding to injury/disease. The osteocyte mechanotransduction pathway, and the downstream effects it mediates, is highly complex. In vivo models have proved invaluable in understanding this process. This review summarizes the commonly used models, as well as more recently developed ones, and describes how they are used to address emerging questions in the field.Rec...
Source: Current Osteoporosis Reports - November 8, 2018 Category: Orthopaedics Source Type: research

Fibula: The Forgotten Bone —May It Provide Some Insight On a Wider Scope for Bone Mechanostat Control?
AbstractThe human fibula responds to its mechanical environment differently from the tibia accordingly with foot usage. Fibula structure is unaffected by disuse, and is stronger concerning lateral bending in soccer players (who evert and rotate the foot) and weaker in long-distance runners (who jump while running) with respect to untrained controls, along the insertion region of peroneus muscles. These features, strikingly associated to the abilities of the fibulae of predator and prey quadrupeds to manage uneven surfaces and to store elastic energy to jump, respectively, suggest that bone mechanostat would control bone pr...
Source: Current Osteoporosis Reports - November 5, 2018 Category: Orthopaedics Source Type: research

Mineral and Bone Disease in Kidney Transplant Recipients
AbstractPurpose of ReviewDespite metabolic improvements following kidney transplantation, transplant recipients still often suffer from complex mineral and bone disease after transplantation.Recent FindingsThe pathophysiology of post-transplant disease is unique, secondary to underlying pre-transplant mineral and bone disease, immunosuppression, and changing kidney function. Changes in modern immunosuppression regimens continue to alter the clinical picture. Modern management includes reducing cumulative steroid exposure and correcting the biochemical abnormalities in mineral metabolism. While bone mineral density screenin...
Source: Current Osteoporosis Reports - November 3, 2018 Category: Orthopaedics Source Type: research

Mechanisms Underlying Bone and Joint Pain
AbstractPurpose of ReviewThe goal of this review is to provide a broad overview of the current understanding of mechanisms underlying bone and joint pain.Recent FindingsBone or joint pathology is generally accompanied by local release of pro-inflammatory cytokines, growth factors, and neurotransmitters that activate and sensitize sensory nerves resulting in an amplified pain signal. Modulation of the pain signal within the spinal cord and brain that result in net increased facilitation is proposed to contribute to the development of chronic pain.SummaryGreat strides have been made in our understanding of mechanisms underly...
Source: Current Osteoporosis Reports - October 29, 2018 Category: Orthopaedics Source Type: research

Medication Decision-making in Osteoporosis: Can We Explain Why Patients Do Not Take Their Osteoporosis Medications?
AbstractPatients at high risk of fracture often do not take medication for osteoporosis. Recent literature may give us some insights into why patients at high risk of fracture do not take medications for osteoporosis. (Source: Current Osteoporosis Reports)
Source: Current Osteoporosis Reports - October 29, 2018 Category: Orthopaedics Source Type: research

Importance of Recent Fracture as Predictor of Imminent Fracture Risk
AbstractPurpose of ReviewTo examine the importance of recent fracture as a predictor of imminent fracture risk, review the importance of prior fracture type and timing, and identify risk factors for recurrent osteoporotic fracture.Recent FindingsPrior fracture type and timing impact risk of subsequent fracture that is largely independent of bone mineral density. Site of re-fracture is similar to original major osteoporotic fracture. Incidence of recurrent major osteoporotic fracture is greatest within the first year. Other risk factors include those that pertain to individual characteristics. Approved osteoporosis therapie...
Source: Current Osteoporosis Reports - October 27, 2018 Category: Orthopaedics Source Type: research

Updates in CKD-Associated Osteoporosis
AbstractPurpose of ReviewChronic kidney disease (CKD) is associated with bone loss and fractures. The purpose of this review is to provide clinicians with an overview of the underlying pathogenesis of CKD-associated osteoporosis, and a summary of the current diagnostic and therapeutic approaches to this disease.Recent FindingsIn 2017, the Kidney Disease Improving Global Outcomes Committee on Bone Quality updated their guidelines to include screening for osteoporosis and fracture risk by dual energy X-ray absorptiometry in patients with CKD. Once a diagnosis of osteoporosis and/or fracture risk is established, it is not cle...
Source: Current Osteoporosis Reports - October 23, 2018 Category: Orthopaedics Source Type: research

Non-renal-Related Mechanisms of FGF23 Pathophysiology
AbstractPurpose of ReviewWe will review non-renal-related mechanisms of fibroblast growth factor 23 (FGF23) pathophysiology.Recent FindingsFGF23 production and metabolism may be affected by many bone, mineral, and kidney factors. However, it has recently been demonstrated that other factors, such as iron status, erythropoietin, and inflammation, also affect FGF23 production and metabolism. As these non-mineral factors are especially relevant in the setting of chronic kidney disease (CKD), they may represent emerging determinants of CKD-associated elevated FGF23 levels. Moreover, FGF23 itself may promote anemia and inflamma...
Source: Current Osteoporosis Reports - October 23, 2018 Category: Orthopaedics Source Type: research

Celiac Disease —Musculoskeletal Manifestations and Mechanisms in Children to Adults
AbstractPurpose of ReviewWe aim to review the current literature on the association of musculoskeletal disorders and celiac disease that is a common disorder, affecting about 1% of the population. Extra-intestinal symptoms and presentations predominate.Recent FindingsWhile the literature supports an association with reduced bone mineral density and increased fracture risk and celiac disease, there is little evidence supporting associations with other rheumatological conditions. Patients frequently report musculoskeletal symptoms; however, studies of specific disease entities suffer from a lack of standardization of testing...
Source: Current Osteoporosis Reports - October 22, 2018 Category: Orthopaedics Source Type: research

Crosstalk Between Sensory Nerves and Cancer in Bone
AbstractPurpose of ReviewSensory nerves (SNs) richly innervate bone and are a component of bone microenvironment. Cancer metastasis in bone, which is under the control of the crosstalk with bone microenvironment, induces bone pain via excitation of SNs innervating bone. However, little is known whether excited SNs in turn affect bone metastasis.Recent FindingsCancer cells colonizing bone promote neo-neurogenesis of SNs and excite SNs via activation of the acid-sensing nociceptors by creating pathological acidosis in bone, evoking bone pain. Denervation of SNs or inhibition of SN excitation decreases bone pain and cancer pr...
Source: Current Osteoporosis Reports - October 20, 2018 Category: Orthopaedics Source Type: research

Gonadal Hormones in the Pathogenesis and Treatment of Bone Health in Patients with Chronic Kidney Disease: a Systematic Review and Meta-Analysis
AbstractPurpose of ReviewPatients with chronic kidney disease (CKD) have a greatly increased fracture risk compared with the general population. Gonadal hormones have an important influence on bone mineral density (BMD) and fracture risk, and hormone therapies can significantly improve these outcomes. Gonadal dysfunction is a frequent finding in patients with CKD; yet, little is known about the impact of gonadal hormones in the pathogenesis and treatment of bone health in patients with CKD. This systematic review and meta-analysis aimed to examine the effects of gonadal hormones and hormone therapies on bone outcomes in me...
Source: Current Osteoporosis Reports - October 17, 2018 Category: Orthopaedics Source Type: research

CKD-MBD: from the Pathogenesis to the Identification and Development of Potential Novel Therapeutic Targets
AbstractPurpose of ReviewAlthough we have seen tremendous advances in the comprehension of CKD-MBD pathophysiology during the last few years, this was not accompanied by a significant change in mortality rate and quality of life. This review will address the traditional and updated pathophysiology of CKD-MBD along with the therapeutic limitations that affect CKD-MBD and proposed alternative treatment targets.Recent FindingsAn innovative concept brings the osteocyte to the center of CKD-MBD pathophysiology, in contrast to the traditional view of the skeleton as a target organ for disturbances in calcium, phosphate, parathyr...
Source: Current Osteoporosis Reports - October 5, 2018 Category: Orthopaedics Source Type: research

PET-MRI for the Study of Metabolic Bone Disease
AbstractPurpose of ReviewThis review article attempts to summarize the current state and applications of the hybrid imaging modality of PET-MRI to metabolic bone diseases. The advances of PET and MRI are also discussed for metabolic bone diseases as potentially applied via PET-MRI.Recent FindingsEtiologies and mechanisms of metabolic bone disease can be complex where molecular changes precede structural changes. Although PET-MRI has yet to be applied directly to metabolic bone disease, possible applications exist since PET, specifically18F-NaF PET, can quantitatively track changes in bone metabolism and is useful for asses...
Source: Current Osteoporosis Reports - October 4, 2018 Category: Orthopaedics Source Type: research

Recent Progress in Sarcopenia Research: a Focus on Operationalizing a Definition of Sarcopenia
AbstractPurpose of ReviewTo discuss recent progress in sarcopenia research and to highlight controversies in the field particularly around reaching consensus on a definition of sarcopenia.Recent FindingsAccordingly, this review begins with a discussion of the increasing awareness of this condition; briefly describes evolving definitions of sarcopenia; suggests a framework for consistent terminology for sarcopenia; discusses outstanding issues in the definition of sarcopenia; and reviews the association between sarcopenia and adverse outcome in older adults. In addition, the role of sarcopenia in other diseases is discussed...
Source: Current Osteoporosis Reports - October 3, 2018 Category: Orthopaedics Source Type: research

The Influence of Cortical Porosity on the Strength of Bone During Growth and Advancing Age
AbstractPurpose of ReviewBone densitometry provides a two-dimensional projected areal apparent bone mineral density that fails to capture the heterogeneity of bone ’s material composition and macro-, micro-, and nano-structures critical to its material and structural strength. Assessment of the structural basis of bone fragility has focused largely on trabecular bone based on the common occurrence of fragility fractures at sites with substantial amounts of t rabecular bone. This review focuses on the contribution of cortical bone to bone fragility throughout life.Recent FindingsAccurately differentiating cortical and...
Source: Current Osteoporosis Reports - October 1, 2018 Category: Orthopaedics Source Type: research

Cortical Bone Mapping: Measurement and Statistical Analysis of Localised Skeletal Changes
AbstractPurpose of ReviewCortical bone mapping (CBM) is a technique for measuring localised skeletal changes from computed tomography (CT) images. It can provide measurements with accuracy surpassing the underlying imaging resolution. CBM can detect changes in several properties of the cortex, with no prior assumptions about the likely location of said changes. This paper summarises the theory behind CBM, discusses its strengths and limitations, and reviews some studies in which it has been applied.Recent FindingsCBM has revealed associations between fracture risk and cortical properties in specific regions of the proximal...
Source: Current Osteoporosis Reports - October 1, 2018 Category: Orthopaedics Source Type: research

Targeting the Muscle-Bone Unit: Filling Two Needs with One Deed in the Treatment of Duchenne Muscular Dystrophy
AbstractPurpose of ReviewIn Duchenne muscular dystrophy (DMD), the progressive skeletal and cardiac muscle dysfunction and degeneration is accompanied by low bone mineral density and bone fragility. Glucocorticoids, which remain the standard of care for patients with DMD, increase the risk of developing osteoporosis. The scope of this review emphasizes the mutual cohesion and common signaling pathways between bone and skeletal muscle in DMD.Recent FindingsThe muscle-bone interactions involve bone-derived osteokines, muscle-derived myokines, and dual-origin cytokines that trigger common signaling pathways leading to fibrosi...
Source: Current Osteoporosis Reports - October 1, 2018 Category: Orthopaedics Source Type: research

Vertebral Fracture Identification as Part of a Comprehensive Risk Assessment in Patients with Osteoporosis
AbstractPurpose of ReviewTo review current evidence regarding the vertebral fracture prevalence, the accuracy of vertebral fracture identification on current imaging technologies, and the potential impact of vertebral fracture identification on fracture risk.Recent FindingsImportant new studies have clarified the features of prevalent vertebral fracture that most strongly predict incident fractures. Age- and sex-stratified estimates of vertebral fracture prevalence on densitometric lateral spine images in the US population are now available. The accuracy of densitometric vertebral fracture assessment, how computed tomograp...
Source: Current Osteoporosis Reports - October 1, 2018 Category: Orthopaedics Source Type: research

Current Understanding of the Pathophysiology of Osteonecrosis of the Jaw
This article raises the current theories under lying the pathophysiology of ONJ.Recent FindingsThe proposed mechanisms highlight the unique localization of ONJ. The evidence-based mechanisms of ONJ pathogenesis include disturbed bone remodeling, inflammation or infection, altered immunity, soft tissue toxicity, and angiogenesis inhibition. The role of dental infections and the oral microbiome is central to ONJ, and systemic conditions such as rheumatoid arthritis and diabetes mellitus contribute through their impact on immune resiliency.SummaryCurrent experimental studies on mechanisms of ONJ are summarized. The definitive...
Source: Current Osteoporosis Reports - October 1, 2018 Category: Orthopaedics Source Type: research

Using Mendelian Randomization to Decipher Mechanisms of Bone Disease
AbstractPurpose of ReviewThis review summarizes the basic principles of Mendelian randomization (MR) and provides evidence for the causal effect of multiple modifiable factors on bone outcomes.Recent FindingsSeveral studies using MR approach have provided support for the causal effect of obesity on bone mineral density (BMD). Strikingly, studies have failed to prove a causal association between elevated 25(OH) D concentrations and higher BMD in community-dwelling individuals.SummaryThe MR approach has been successfully used to evaluate multiple factors related to bone mineral density variation and/or fracture risk. The MR ...
Source: Current Osteoporosis Reports - October 1, 2018 Category: Orthopaedics Source Type: research

Mechanisms of Osteoarthritis (OA) Pain
AbstractPurpose of ReviewOsteoarthritis (OA) is a major cause of pain and disability worldwide. There is, however, a relatively poor correlation between the severity of OA based on plain radiograph changes and symptoms. In this review, we consider the mechanisms of pain in OA.Recent FindingsIt is now widely recognised that OA is a disease of the whole joint. Data from large observational studies which have used magnetic resonance imaging (MRI) suggest that pain in OA is associated with a number of structural factors including the presence of bone marrow lesions (BMLs) and also synovitis. There is evidence also of alteratio...
Source: Current Osteoporosis Reports - October 1, 2018 Category: Orthopaedics Source Type: research

Interactions Between Disseminated Tumor Cells and Bone Marrow Stromal Cells Regulate Tumor Dormancy
AbstractPurpose of ReviewTo succinctly summarize recent findings concerning dormancy regulating interactions between bone marrow stromal cells and disseminated tumor cells.Recent FindingsRecent studies have highlighted roles of the bone marrow microenviroment, including osteoblasts, mesenchymal stem cells (MSCs), and endothelial cells, in inducing or maintaining cancer cell dormancy. Key pathways of interest include: osteoblast-induced transforming growth factor (TGF)- β2 signaling, transfer of MSC-derived exosomes containing dormancy inducing microRNA, cancer cell cannibalism of MSCs, and endothelial cell secretion o...
Source: Current Osteoporosis Reports - October 1, 2018 Category: Orthopaedics Source Type: research

Carbon Nanomaterials for Treating Osteoporotic Vertebral Fractures
This study, therefore, has opened our perspectives and certainly calls for more attention to the use of carbon nanomaterials for a wide range of osteoporosis applications. (Source: Current Osteoporosis Reports)
Source: Current Osteoporosis Reports - October 1, 2018 Category: Orthopaedics Source Type: research

The Effects of Homocysteine on the Skeleton
AbstractPurpose of ReviewHomocystinuria is a congenital metabolic disorder in which cystathionine β-synthase deficiency results in a prominent increase in homocysteine (serum levels>  100 μM), causing mental retardation, atherosclerotic cerebral infarction, and osteoporosis accompanied by fragility fractures. Encountering a case with excessive homocysteinemia such as that seen in hereditary homocystinuria is unlikely during usual medical examinations. However, in individuals who have vitamin B or folate deficiency, serum homocysteine concentrations are known to increase. These individuals may also ha...
Source: Current Osteoporosis Reports - October 1, 2018 Category: Orthopaedics Source Type: research