MicroRNAs and Their Roles in Breast Cancer Bone Metastasis
AbstractBone metastasis occurs in advanced stages of breast cancer, worsening the quality of life and increasing the mortality of patients. Current treatments for bone metastasis are only palliative, and efficient therapeutic targets need to be still identified. MicroRNAs (miRNAs) are a large class of small non-coding RNAs that regulate gene expression within cells. Interestingly, the expression of certain miRNAs has been associated with several stages of bone metastasis progression, highlighting the importance of these small RNAs during the course of the metastatic disease. In this review, we aim to summarise the most rec...
Source: Current Osteoporosis Reports - April 8, 2021 Category: Orthopaedics Source Type: research
Current Analysis of Skeletal Phenotypes in Down Syndrome
AbstractPurposeDown syndrome (DS) is caused by trisomy 21 (Ts21) and results in skeletal deficits including shortened stature, low bone mineral density, and a predisposition to early onset osteoporosis. Ts21 causes significant alterations in skeletal development, morphology of the appendicular skeleton, bone homeostasis, age-related bone loss, and bone strength. However, the genetic or cellular origins of DS skeletal phenotypes remain unclear.Recent FindingsNew studies reveal a sexual dimorphism in characteristics and onset of skeletal deficits that differ between DS and typically developing individuals. Age-related bone l...
Source: Current Osteoporosis Reports - April 8, 2021 Category: Orthopaedics Source Type: research
Role of Osteocytes in Cancer Progression in the Bone and the Associated Skeletal Disease
AbstractPurpose of ReviewThe goal of this manuscript is to review the current knowledge on the role of osteocytes in cancer in the bone, discuss the potential of osteocytes as a therapeutic target, and propose future research needed to understand the crosstalk between cancer cells and osteocytes in the tumor niche.Recent FindingsNumerous studies have established that cancer cells manipulate osteocytes to facilitate invasion and tumor progression in bone. Moreover, cancer cells dysregulate osteocyte function to disrupt physiological bone remodeling, leading to the development of bone disease. Targeting osteocytes and their ...
Source: Current Osteoporosis Reports - April 5, 2021 Category: Orthopaedics Source Type: research
Skeletal Functions of Voltage Sensitive Calcium Channels
AbstractSummaryVoltage-sensitive calcium channels (VSCCs) are ubiquitous multimeric protein complexes that are necessary for the regulation of numerous physiological processes. VSCCs regulate calcium influx and various intracellular processes including muscle contraction, neurotransmission, hormone secretion, and gene transcription, with function specificity defined by the channel ’s subunits and tissue location.The functions of VSCCs in bone are often overlooked since bone is not considered an electrically excitable tissue. However, skeletal homeostasis and adaptation relies heavily on VSCCs. Inhibition or deletion of V...
Source: Current Osteoporosis Reports - March 15, 2021 Category: Orthopaedics Source Type: research
Targeting Histone Modifications in Bone and Lung Metastatic Cancers
AbstractPurpose of ReviewBreast cancer frequently metastasizes to the bone and lung, but the ability to treat metastatic tumor cells remains a pressing clinical challenge. Histone deacetylases (HDACs) and histone acetyltransferases (HATs) have emerged as promising targets since these enzymes are aberrantly expressed in numerous cancers and regulate the expression of genes that drive tumorigenesis and metastasis. This review focuses on the abnormal expression of histone-modifying enzymes in cancers that have a high tropism for the bone and lung and explores the clinical use of histone deacetylase inhibitors for the treatmen...
Source: Current Osteoporosis Reports - March 15, 2021 Category: Orthopaedics Source Type: research
Osteogenesis Imperfecta —Who Needs Rodding Surgery?
AbstractPurpose of ReviewThe purpose of this review is to precise the indications for intramedullary rodding of long bones in osteogenesis imperfecta, the classic treatment for fractures and deformities in this condition.Recent FindingsThe use of plates and screws alone is not recommended, but its use in conjunction with rodding is becoming more popular as demonstrated in recent literature. The different types of rods are reviewed and their advantages/disadvantages exposed. There is a clear advantage for telescopic rods in terms of incidence of revision surgery but complications are still to be expected.SummaryAn interdisc...
Source: Current Osteoporosis Reports - March 1, 2021 Category: Orthopaedics Source Type: research
Extracellular Vesicles and Bone-Associated Cancer
AbstractPurpose of ReviewIn this review, we describe the biology of extracellular vesicles (EV) and how they contribute to bone-associated cancers.Recent FindingsCrosstalk between tumor and bone has been demonstrated to promote tumor and metastatic progression. In addition to direct cell-to-cell contact and soluble factors, such as cytokines, EVs mediate crosstalk between tumor and bone. EVs are composed of a heterogenous group of membrane-delineated vesicles of varying size range, mechanisms of formation, and content. These include apoptotic bodies, microvesicles, large oncosomes, and exosomes. EVs derived from primary tu...
Source: Current Osteoporosis Reports - February 27, 2021 Category: Orthopaedics Source Type: research
Biomechanical Basis of Predicting and Preventing Lower Limb Stress Fractures During Arduous Training
AbstractPurpose of ReviewStress fractures at weight-bearing sites, particularly the tibia, are common in military recruits and athletes. This review presents recent findings from human imaging and biomechanics studies aimed at predicting and preventing stress fractures.Recent FindingsPeripheral quantitative computed tomography (pQCT) provides evidence that cortical bone geometry (tibial width and area) is associated with tibial stress fracture risk during weight-bearing exercise. The contribution of bone trabecular microarchitecture, cortical porosity, and bone material properties in the pathophysiology of stress fractures...
Source: Current Osteoporosis Reports - February 26, 2021 Category: Orthopaedics Source Type: research
Preventing Bone Stress Injuries in Runners with Optimal Workload
AbstractBone stress injuries (BSIs) occur at inopportune times to invariably interrupt training. All BSIs in runners occur due to an “error” in workload wherein the interaction between the number and magnitude of bone tissue loading cycles exceeds the ability of the tissue to resist the repetitive loads. There is not a single optimal bone workload, rather a range which is influenced by the prevailing scenario. In prepubertal athletes, optimal bone workload consists of low-repetitions of fast, high-magnitude, multidirectional loads introduced a few times per day to induce bone adaptation. Premature sports specialization...
Source: Current Osteoporosis Reports - February 26, 2021 Category: Orthopaedics Source Type: research
Anabolic Agents for Postmenopausal Osteoporosis: How Do You Choose?
AbstractPurpose of ReviewThere are now three anabolic agents available for the treatment of postmenopausal women at high risk for fracture. The purpose of this review is to supply a rationale to aid in determining which agent should be used in which clinical settings.Recent FindingsStudies over the last decade have shown that anabolic agents produce faster and larger effects against fracture than antiresorptive agents. Furthermore, trials evaluating anabolic antiresorptive treatment sequences have shown that anabolic first treatment strategies produce the greatest benefits to bone density, particularly in the hip region. H...
Source: Current Osteoporosis Reports - February 26, 2021 Category: Orthopaedics Source Type: research
Denosumab Treatment for Giant Cell Tumors, Aneurysmal Bone Cysts, and Fibrous Dysplasia —Risks and Benefits
AbstractPurpose of ReviewThis review summarizes current understanding of the role of denosumab, an inhibitor of receptor activator of nuclear kappa-B ligand (RANKL), in the management of 3 skeletal neoplasms: giant cell tumors, aneurysmal bone cysts, and fibrous dysplasia.Recent FindingsA growing body of literature supports denosumab use in giant cell tumors, a neoplasm in which RANKL plays a clear pathogenic role. Comparatively less data is available in aneurysmal bone cysts and fibrous dysplasia; however, the pathogenic similarity of these disorders to giant cell tumors, as well as encouraging preliminary data, suggests ...
Source: Current Osteoporosis Reports - February 22, 2021 Category: Orthopaedics Source Type: research
Applications of Lipidomics to Age-Related Musculoskeletal Disorders
AbstractPurpose of ReviewThe goal of this review is to highlight the need for new biomarkers for the diagnosis and treatment of musculoskeletal disorders, especially osteoporosis and sarcopenia. These conditions are characterized by loss of bone and muscle mass, respectively, leading to functional deterioration and the development of disabilities. Advances in high-resolution lipidomics platforms are being used to help identify new lipid biomarkers for these diseases.Recent FindingsIt is now well established that bone and muscle have important endocrine functions, including the release of bioactive factors in response to me...
Source: Current Osteoporosis Reports - February 16, 2021 Category: Orthopaedics Source Type: research
The Genetics of Atypical Femur Fractures —a Systematic Review
AbstractPurpose of ReviewAtypical femur fractures (AFFs) are rare subtrochanteric or diaphyseal fractures regarded as side effects of bisphosphonates (BPs), possibly with a genetic background. Here, we summarize the most recent knowledge about genetics of AFFs.Recent FindingsAFF has been reported in 57 patients with seven different monogenic bone disorders including hypophosphatasia and osteogenesis imperfecta; 56.1% had never used BPs, while 17.5% were diagnosed with the disorder only after the AFF. Gene mutation finding in familial and sporadic cases identified possible AFF-related variants in theGGPS1 andATRAID genes re...
Source: Current Osteoporosis Reports - February 15, 2021 Category: Orthopaedics Source Type: research
Dietary Patterns and Pediatric Bone
AbstractPurpose of ReviewMuch of what we know about dietary patterns (DPs) and bone is derived from cross-sectional studies in adults. Given, establishing healthy bones during childhood serves as a blueprint for adult bone, it is important to better understand the role of DPs on pediatric bone. The purpose of this review is to determine if DPs influence bone strength in children.Recent FindingsThe majority of studies investigating the role of DPs on pediatric bone are cross-sectional in design and examine data-derived “a posterori” DPs. Overall, the DPs characterized by high intakes of fruits and vegetables demonstrate...
Source: Current Osteoporosis Reports - February 11, 2021 Category: Orthopaedics Source Type: research
Single Cell Omics for Musculoskeletal Research
This article summarizes talks given during a workshop on “Single Cell Omics” at the 2020 annual meeting of the Orthopedic Research Society. Studies that applied scRNA-seq, ATAC-seq, and CyTOF mass cytometry to cartilage development and osteoarthritis are reviewed. This body of work shows how these cutting-edge tools can advance our understanding of th e cellular heterogeneity and trajectories of lineage specification during development and disease. (Source: Current Osteoporosis Reports)
Source: Current Osteoporosis Reports - February 9, 2021 Category: Orthopaedics Source Type: research
