Current Osteoporosis Reports最新文献

Purpose of review: In this review, we summarize our evolving understanding of the epigenetic mechanisms directing the osteogenic differentiation of skeletal progenitor cells.

Recent findings: Advances in genome-wide approaches used to profile chromatin accessibility and histone modifications in skeletal progenitors have uncovered chromatin remodeling associated with progression of osteoblast differentiation and the key regulatory nodes driving this process. Utilization of cell culture systems and genetic mouse models highlight the key enzymes regulating histone posttranslational modifications and DNA methylation that promote the transition of cells from progenitor to mature osteoblast stage. Herein, the described studies provide emerging insights gained from pharmacologic targeting of chromatin modifiers promoting osteogenic differentiation of skeletal progenitors. While our fundamental understanding of chromatin modifiers and factors regulating chromatin accessibility and transcriptional activity in skeletal progenitors continues to develop, future research may inform new therapeutic approaches to promote osteoblast differentiation and enhance mineralization to augment fracture repair.

Purpose of review: To discuss current evidence on the diagnosis and management of osteoporosis in patients with chronic kidney disease (CKD).

Recent findings: Osteoporosis and fractures are prevalent in older CKD patients and associated with poor process indicators and outcomes. While osteoporosis treatment is generally similar in patients without or with CKD up to stage 3, there is still a lack of evidence to guide many areas of osteoporosis management in CKD stages 4-5. There is an urgent need to establish local multidisciplinary care pathways for CKD and dialysis patients with osteoporosis, involving nephrologists, bone specialists and fracture liaison services. Optimization of calcium and vitamin D metabolism and non-pharmacological measures including exercise and falls prevention should be considered in all patients. Withholding bone drugs solely based on glomerular filtration rates may constitute renalism (discrimination based on kidney function), which would further widen the already large treatment gap in osteoporosis. On the other hand, more evidence is needed to inform almost every aspect of anti-osteoporotic pharmacotherapy in CKD stages 4-5. The concept of choosing between antiresorptive or anabolic bone drugs based on a pre-treatment assessment of bone turnover (using biomarkers or bone biopsies), is a dogma in urgent need of critical re-evaluation. This narrative review aims to summarize our current understanding of the management of CKD-associated osteoporosis and fracture prevention in stage 4-5 CKD patients.

Purpose of review: Genome-wide association studies (GWAS) have significantly advanced osteoporosis research by identifying genetic loci associated with bone mineral density (BMD) and fracture risk. However, disparities persist due to the underrepresentation of non-European populations, limiting the applicability of polygenic risk scores (PRS). This review examines recent advancements in osteoporosis genetics, highlights existing disparities, and explores strategies for more inclusive research.

Recent findings: European-focused GWAS have identified key loci for osteoporosis, including WNT signaling (SOST, LRP5) and RUNX2 transcriptional regulation. However, fewer than 40% of these variants can be replicated in Asian and African populations. Emerging studies in non-European groups reveal population-specific loci, sex-specific associations, and gene-environment interactions. Advances in machine learning (ML)-assisted GWAS and multi-omics integration are improving genetic discovery. Expanding GWAS in diverse populations, integrating multi-omics data, refining ML-based risk models, and standardizing biobank data are essential for equitable osteoporosis research. Future efforts must prioritize clinical translation to enhance personalized osteoporosis prevention and treatment.

Purpose of review: This review explores the role of cell communication network (CCN) proteins in regulating skeletal physiology, aging, and disease, particularly within the context of balanced bone remodeling.

Recent findings: Recent conceptualization of paracrine and endocrine networks in bone marrow as a form of osteoimmunological crosstalk suggests a significant role for matricellular signaling in regulating bone homeostasis. As multifunctional adapters of cell-matrix interactions, CCNs are emerging as a focal point for parathyroid hormone (PTH) signaling and regulation of the RANKL/RANK/OPG axis in skeletal aging. Altered bone marrow CCN expression creates a permissive environment for accelerated postmenopausal bone loss and may contribute to the pathogenesis of osteoporosis and other diseases related to skeletal aging. CCNs modulate fundamental signaling mechanisms in bone development, homeostasis and repair. During aging, dysregulation of CCNs may negatively affect skeletal health and contribute to disease progression. As a result, CCNs may constitute promising therapeutic targets for improving and maintaining aging bone health.

Purpose of review: Mechanical loading of bone is an important physical stimulus for bone tissue remodeling and adaptation. It is transmitted from the extracellular matrix all the way to the osteocyte nucleus via the extracellular matrix-integrin-cytoskeleton-nucleus system. Mitochondria are integral in sensing of mechanical loads to allow the cell to adapt to its environment. This review provides a background of mitochondrial distribution in osteocytes especially during mechanical loading, discussing the importance of mitochondrial distribution in osteocyte mechanosensitivity and mechanotransduction.

Recent findings: Mitochondria throughout the osteocyte are highly dynamic and provide essential metabolic and signal functions to regulate osteocyte morphology and function. They undergo the processes of fission and fusion accompanied by mitochondrial DNA distribution. The mitochondrial network structure and function in osteocytes can be regulated by mechanical loading. Interestingly, mitochondria can be transmitted by osteocytes into adjacent cells to communicate with them via tunneling nanotubes, migrasomes, and blebbisomes, causing changes in cell morphology and/or function. Mitochondrial distribution in or out osteocytes can be rearranged by physical and (bio)chemical signals via fission and fusion, as well as tunneling nanotubes, migrasomes, and blebbisomes. Mechanical loading-induced changes in mitochondria may drive signaling pathways of cell function in aging and diseases. More insights into interactions between neighbouring osteocytes and between osteocytes and other cell types would facilitate the development of new strategies to apply mitochondrial therapy for bone-related diseases.

Purpose of review: This review summarizes the recently published scientific evidence regarding the role of enzymes engaged in de novo anabolic biosynthesis, catabolic, and salvage pathways of ceramide bioactive sphingolipids in bone dynamics and skeletal health.

Recent findings: Ceramides are precursors for bioactive sphingolipids, including sphingosine, sphingosine-1-phosphate, and others. Studies of bone metabolism and bone-related cells demonstrated that ceramide and sphingosine-1-phosphate control levels of bone remodeling and resorption generated by osteoblasts and osteoclasts. Multiple published studies demonstrated the critical role of enzymes in regulating the ceramide/sphingosine-1-phosphate ratio relative to bone physiology and the promotion of inflammatory osteolysis. Accordingly, emerging evidence suggests that targeting sphingolipid metabolism has the potential to alleviate inflammatory osteolysis and accelerate bone regeneration. Therefore, this study aimed to discuss current knowledge about crosstalk between sphingolipids and their metabolic enzymes within osteoclast and osteoblast coupling in bone remodeling and pathogenic osteolysis. This review highlights the complexity of de novo sphingolipid biosynthesis and knowledge gaps in bone physiology and pathology. We also discuss the importance of canonical and non-canonical mammalian and bacterial-derived sphingolipids relative to bone health.

Purpose of review: This review summarises the latest evidence on effects of exercise on falls prevention, bone mineral density (BMD) and fragility fracture risk in postmenopausal women, explores hypotheses underpinning exercise-mediated effects on BMD and sheds light on innovative concepts to better understand and harness the skeletal benefits of exercise.

Recent findings: Multimodal exercise programs incorporating challenging balance exercises can prevent falls. Emerging clinical trial evidence indicates supervised progressive high-intensity resistance and impact training (HiRIT) is efficacious in increasing lumbar spine BMD and is safe and well-tolerated in postmenopausal women with osteoporosis/osteopenia. There remains uncertainty regarding durability of this load-induced osteogenic response and safety in patients with recent fractures. Muscle-derived myokines and small circulating extracellular vesicles have emerged as potential sources of exercise-induced muscle-bone crosstalk but require validation in postmenopausal women. Exercise has the potential for multi-modal skeletal benefits with i) HiRIT to build bone, and ii) challenging balance exercises to prevent falls, and ultimately fractures. The therapeutic effect of such exercise in combination with osteoporosis pharmacotherapy should be considered in future trials.

Purpose of review: Osteoporosis (OP) is characterized by degraded bone microstructure, loss of bone mass and increased risk of fragility fractures. Currently, T-score determined by dual-energy X-ray absorptiometry (DEXA) measurements has been regarded as the gold standard for the diagnosis of osteoporosis. However, multiple factors have indicated that the T-score is insufficient to identify individuals with osteoporosis at a potentially high risk of fracture, or accurately detect those who require treatment, or continuously monitor the risk of re-fracture and clinical outcomes after treatment. This review covers publications in a range of ten years and comprehensively summarizes the studies in laboratory-based biomarkers for osteoporotic fractures (OF), aiming to provide physicians and surgeons with an update of clinical research in identification, verification and application of these tools, and to provide useful information for the design of future clinical studies.

Recent findings: It was found that bone formation markers (such as PINP, BGP, ECM1 and SOST), bone resorption markers (such as β-CTX, TRAcP5b, osteocalcin, RANKL, RANKL/OPG ratio, and t-PINP/β-CTX), hormonal biomarkers (such as IGF- 1, PTH, leptin, adiponectin and AMH), indicators of inflammation and oxidative stress (SII, IL- 6, LTL, FlOP_360, FlOP_400, and GGT), microRNAs (such as miR- 21, miR- 320a- 3p, miR- 491 - 5p, miR- 485 - 3p, miR- 19b- 1- 5p, miR- 203a, miR- 31 - 5p, miR- 502 - 3p, miR- 4739, miR- 497, miR- 19b, and miR- 107), other biomarkers (SAF-AGEs and glycine), adipocytokines (irisin and Omentin- 1), senescence biomarkers (RDW), and lncRNAs (MIAT) may be useful biomarkers for clinical practice. Further validation of these biomarkers and a better understanding of the underlying molecular mechanisms may help in the development and application of these biomarkers for risk prediction of OF, differential diagnosis among OP, OF and healthy individuals, as well as post-operative monitoring of re-fracture risk and treatment outcomes.

Purpose of review: Osteoporosis is a prevalent skeletal disorder in postmenopausal women and older adults. Kefir has gained attention for its potent antioxidative, anti-inflammatory, and immunomodulatory properties. This review consolidates findings on kefir-derived peptides' interventions in osteoporosis models and evaluates the therapeutic potential of kefir components in preventing osteoporosis, thereby enhancing its application in clinical nutrition strategies for osteoporosis management.

Recent findings: Kefir-derived peptides exhibit osteoprotective potential in various animal models of osteoporosis, in which several antioxidative and ACE-inhibitory peptides have been shown to promote osteoblast differentiation and mineralization. In addition, emerging evidence supports the role of kefir-derived probiotics and exopolysaccharides (kefiran) in mitigating bone loss. Kefir holds significant promise in the management of osteoporosis due to its unique composition of bioactive components promoting bone health. While research is still in its early stages, evidence suggests kefir's potential as a natural approach to osteoporosis prevention and management.