Current Osteoporosis Reports最新文献

Purpose of review: Pseudohypoparathyroidism (PHP) is a disorder caused by mutations and/or epigenetic changes at the complex GNAS locus. It is characterized by hypocalcemia, hyperphosphatemia, and an elevated parathyroid hormone concentration secondary to the resistance of target tissues to the biological actions of parathyroid hormone. PHP is divided into several subtypes with different yet overlapping phenotypes. Research on the bone status in patients with PHP is sparse and has yielded inconsistent results. This review was performed to summarize the current knowledge on the bone phenotypes and possible mechanisms of PHP.

Recent findings: Patients with PHP exhibit highly variable bone phenotypes and increased concentrations of bone turnover markers. Long-standing elevation of the parathyroid hormone concentration may lead to hyperparathyroid bone diseases, including rickets and osteitis fibrosa. Compared with normal controls, patients with PHP may exhibit similar, increased, or decreased bone mineral density. Higher bone mineral density has been found in patients with PHP type 1A than in normal controls, whereas decreased bone mass, osteosclerosis, and osteitis fibrosa cystica have been reported in patients with PHP type 1B, indicating more variable bone phenotypes in PHP type 1B. Bone tissues show partial sensitivity to parathyroid hormone in patients with PHP, leading to heterogeneous reactions to parathyroid hormone in different individuals and even in different regions of bone tissues in the same individual. Regions rich in cancellous bone are more sensitive and show more obvious improvement after therapy. Active vitamin D and calcium can significantly improve abnormal bone metabolism in patients with PHP.

Purpose of the review: The purpose of this review is to summarize the role of the osteocyte in muscle atrophy in cancer patients, sarcopenia, spinal cord injury, Duchenne's muscular dystrophy, and other conditions associated with muscle deterioration.

Recent findings: One type of bone cell, the osteocyte, appears to play a major role in muscle and bone crosstalk, whether physiological or pathological. Osteocytes are cells living within the bone-mineralized matrix. These cells are connected to each other by means of dendrites to create an intricately connected network. The osteocyte network has been shown to respond to different types of stimuli such as mechanical unloading, immobilization, aging, and cancer by producing osteocytes-derived factors. It is now becoming clear that some of these factors including sclerostin, RANKL, TGF-β, and TNF-α have detrimental effects on skeletal muscle. Bone and muscle not only communicate mechanically but also biochemically. Osteocyte-derived factors appear to contribute to the pathogenesis of muscle disease and could be used as a cellular target for new therapeutic approaches.

Purpose of review: To systematically review recent studies investigating the association between metabolites and bone mineral density (BMD) in humans.

Methods: Using predefined keywords, we searched literature published from Jan 1, 2019 to Feb 20, 2022 in PubMed, Web of Science, Embase, and Scopus. Studies that met the predefined exclusion criteria were excluded. Among the included studies, we identified metabolites that were reported to be associated with BMD by at least three independent studies.

Recent findings: A total of 170 studies were retrieved from the databases. After excluding studies that did not meet our predefined inclusion criteria, 16 articles were used in this review. More than 400 unique metabolites in blood were shown to be significantly associated with BMD. Of these, three metabolites were reported by ≥ 3 studies, namely valine, leucine and glycine. Glycine was consistently shown to be inversely associated with BMD, while valine was consistently observed to be positively associated with BMD. Inconsistent associations with BMD was observed for leucine. With advances in metabolomics technology, an increasing number of metabolites associated with BMD have been identified. Two of these metabolites, namely valine and glycine, were consistently associated with BMD, highlighting their potential for clinical application in osteoporosis. International collaboration with a larger population to conduct clinical studies on these metabolites is warranted. On the other hand, given that metabolomics could be affected by genetics and environmental factors, whether the inconsistent association of the metabolites with BMD is due to the interaction between metabolites and genes and/or lifestyle warrants further study.

Purpose of review: Circular RNAs (circRNAs) are RNA transcripts derived from fragments of pre-messenger RNAs through a back-splicing process. An advantage that rises from their circular covalently closed conformation is their high stability, when compared with their linear counterparts. The current review focuses on the emerging roles of circRNAs in osteoporosis, including in osteogenic differentiation and osteoclastogenesis. Their potential as osteoporosis biomarkers will also be discussed.

Recent findings: Although firstly described as non-coding, some of these single-stranded RNAs were recently reported to possess protein-coding capacity. On the other hand, the circRNAs exhibit cell and tissue-specific patterns at the transcriptome level in eukaryotes and are regulated throughout the development or disease progression. Even though thousands of these circular transcripts are listed and annotated, only a limited number of studies describe their biological role in bone processes. Recent evidence indicates inhibitory activator roles in both osteoblasts and osteoclasts differentiation and function. Latest screenings in the blood, plasma, or serum of osteoporosis patients support the potential for circRNA signature to be used as biomarkers in osteoporosis, but further validation is required. While intense research into circRNAs has been detailing their biological roles, there remains a need for standardization and further research to fulfil the future potential of this emerging and highly promising class of regulatory molecules.

Purpose of review: The purpose of this review is to summarize insights gained by finite element (FE) model-based mechanical biomarkers of bone for in vivo assessment of bone development and adaptation, fracture risk, and fracture healing.

Recent findings: Muscle-driven FE models have been used to establish correlations between prenatal strains and morphological development. Postnatal ontogenetic studies have identified potential origins of bone fracture risk and quantified the mechanical environment during stereotypical locomotion and in response to increased loading. FE-based virtual mechanical tests have been used to assess fracture healing with higher fidelity than the current clinical standard; here, virtual torsion test data was a better predictor of torsional rigidity than morphometric measures or radiographic scores. Virtual mechanical biomarkers of strength have also been used to deepen the insights from both preclinical and clinical studies with predictions of strength of union at different stages of healing and reliable predictions of time to healing. Image-based FE models allow for noninvasive measurement of mechanical biomarkers in bone and have emerged as powerful tools for translational research on bone. More work to develop nonirradiating imaging techniques and validate models of bone during particularly dynamic phases (e.g., during growth and the callus region during fracture healing) will allow for continued progress in our understanding of how bone responds along the lifespan.

Purpose of review: This review surveys recent literature related to cortical bone fracture mechanics and its application towards understanding bone fragility and hip fractures.

Recent findings: Current clinical tools for hip fracture risk assessment have been shown to be insensitive in some cases of elevated fracture risk leading to the question of what other factors account for fracture risk. The emergence of cortical bone fracture mechanics has thrown light on other factors at the tissue level that are important to bone fracture resistance and therefore assessment of fracture risk. Recent cortical bone fracture toughness studies have shown contributions from the microstructure and composition towards cortical bone fracture resistance. A key component currently overlooked in the clinical evaluation of fracture risk is the importance of the organic phase and water to irreversible deformation mechanisms that enhance the fracture resistance of cortical bone. Despite recent findings, there is an incomplete understanding of which mechanisms lead to the diminished contribution of the organic phase and water to the fracture toughness in aging and bone-degrading diseases. Notably, studies of the fracture resistance of cortical bone from the hip (specifically the femoral neck) are few, and those that exist are mostly consistent with studies of bone tissue from the femoral diaphysis. Cortical bone fracture mechanics highlights that there are multiple determinants of bone quality and therefore fracture risk and its assessment. There is still much more to learn concerning the tissue-level mechanisms of bone fragility. An improved understanding of these mechanisms will allow for the development of better diagnostic tools and therapeutic measures for bone fragility and fracture.

Purpose of review: This review identifies exercise-based recommendations to prevent and manage frailty and fragility fractures from current clinical practice guidelines. We also critically assess recently published literature in relation to exercise interventions to mitigate frailty and fragility fractures.

Recent findings: Most guidelines presented similar recommendations that included the prescription of individually tailored, multicomponent exercise programs, discouragement of prolonged sitting and inactivity, and combining exercise with optimal nutrition. To target frailty, guidelines recommend supervised progressive resistance training (PRT). For osteoporosis and fragility fractures, exercise should include weight-bearing impact activities and PRT to target bone mineral density (BMD) at the hip and spine, and also incorporate balance and mobility training, posture exercises, and functional exercise relevant to activities of daily living to reduce falls risk. Walking as a singular intervention has limited benefits for frailty and fragility fracture prevention and management. Current evidence-based clinical practice guidelines for frailty, osteoporosis, and fracture prevention recommend a multifaceted and targeted approach to optimise muscle mass, strength, power, and functional mobility as well as BMD.

Purpose of review: The purpose of this review is to summarize the recently published findings regarding the role of epithelial to mesenchymal transition (EMT) in tumor progression, macrophages in the tumor microenvironment, and crosstalk that exists between tumor cells and macrophages.

Recent findings: EMT is a crucial process in tumor progression. In association with EMT changes, macrophage infiltration of tumors occurs frequently. A large body of evidence demonstrates that various mechanisms of crosstalk exist between macrophages and tumor cells that have undergone EMT resulting in a vicious cycle that promotes tumor invasion and metastasis. Tumor-associated macrophages and tumor cells undergoing EMT provide reciprocal crosstalk which leads to tumor progression. These interactions provide potential targets to exploit for therapy.

Purpose of the review: Bone adapts structure and material properties in response to its mechanical environment, a process called mechanoadpatation. For the past 50 years, finite element modeling has been used to investigate the relationships between bone geometry, material properties, and mechanical loading conditions. This review examines how we use finite element modeling in the context of bone mechanoadpatation.

Recent findings: Finite element models estimate complex mechanical stimuli at the tissue and cellular levels, help explain experimental results, and inform the design of loading protocols and prosthetics. FE modeling is a powerful tool to study bone adaptation as it complements experimental approaches. Before using FE models, researchers should determine whether simulation results will provide complementary information to experimental or clinical observations and should establish the level of complexity required. As imaging technics and computational capacity continue increasing, we expect FE models to help in designing treatments of bone pathologies that take advantage of mechanoadaptation of bone.

Purpose of review: This study aims to review diagnosis, potential complications, and clinical management in craniofacial fibrous dysplasia.

Recent findings: Fibrous dysplasia (FD) is a rare mosaic disorder in which normal bone and marrow are replaced with expansile fibro-osseous lesions. Disease presents along a broad spectrum and may be associated with extraskeletal features as part of McCune-Albright syndrome (MAS). The craniofacial skeleton is one of the most commonly impacted areas in FD, and its functional and anatomical complexities create unique challenges for diagnosis and management. This review summarizes current approaches to diagnosis and management in FD/MAS, with emphasis on the clinical and therapeutic implications for the craniofacial skeleton.