Current Osteoporosis Reports最新文献

Purpose of review: Once prostate cancer (PCa) bone metastases develop, the prognosis dramatically declines. The precise mechanisms regulating bone metastasis remain elusive. This review will explore recent findings related to cytokines and chemokines in the process of bone metastases.

Recent findings: We discuss the role of cytokines in tumor growth, invasion, bone remodelling and angiogenesis and immune regulation in PCa skeletal metastases. Major advances in our understanding focus on immune evasion, immune checkpoint blockade, tumor-associated macrophages (TAMs), CAR-T cells, cytokine regulation of matrix metalloproteinases, cytokines including IL-10, IL-27, Interferon-γ, prostate transmembrane protein androgen induced 1 (Pmepa1), and regulation of RUNX2 transcription in supporting survival and growth of disseminated tumor cells (DTCs) and metastases development. The review highlights the complexity of cytokine actions in PCa bone metastases, suggesting potential therapeutic targets to disrupt interactions between cancer cells and their microenvironment.

Purpose of review: Sarcopenia, generally characterized by the age-related reduction in muscle strength, lean/muscle mass and functional ability, is also associated with reduced bone mass and strength and impaired brain health and function. One potential intervention which has received much 'hype' over the past few decades to countermeasure these negative consequences of biological aging is creatine monohydrate supplementation.

Recent findings: From a skeletal muscle perspective, the combination of creatine monohydrate supplementation and resistance training provides 'hope' for older adults as it improves measures of lean mass, regional (limb) muscle thickness, upper- and lower-body muscle strength and functional ability. Further, there is some evidence that creatine (supplementation or habitual diet) provides a ray of 'hope' for improving some aspects of cognitive function. The majority of research suggests that creatine is more 'hype' than 'hope' for improving measures of bone mass in older adults. Creatine monohydrate supplementation provides some anti-sarcopenic benefits for older adults.

Purpose of review: This comprehensive review discusses the complex relationship between Alzheimer's disease (AD) and osteoporosis, two conditions that are prevalent in the aging population and result in adverse complications on quality of life. The purpose of this review is to succinctly elucidate the many commonalities between the two conditions, including shared pathways, inflammatory and oxidative mechanisms, and hormonal deficiencies.

Recent findings: AD and osteoporosis share many aspects of their respective disease-defining pathophysiology. These commonalities include amyloid beta deposition, the Wnt/β-catenin signaling pathway, and estrogen deficiency. The shared mechanisms and risk factors associated with AD and osteoporosis result in a large percentage of patients that develop both diseases. Previous literature has established that the progression of AD increases the risk of sustaining a fracture. Recent findings demonstrate that the reverse may also be true, suggesting that a fracture early in the life course can predispose one to developing AD due to the activation of these shared mechanisms. The discovery of these commonalities further guides the development of novel therapeutics in which both conditions are targeted. This detailed review delves into the commonalities between AD and osteoporosis to uncover the shared players that bring these two seemingly unrelated conditions together. The discussion throughout this review ultimately posits that the occurrence of fractures and the mechanism behind fracture healing can predispose one to developing AD later on in life, similar to how AD patients are at an increased risk of developing fractures. By focusing on the shared mechanisms between AD and osteoporosis, one can better understand the conditions individually and as a unit, thus informing therapeutic approaches and further research. This review article is part of a series of multiple manuscripts designed to determine the utility of using artificial intelligence for writing scientific reviews.

Purpose of the review: Osteosarcopenia is a geriatric syndrome associated with disability and mortality. This review summarizes the key microRNAs that regulate the hallmarks of sarcopenia and osteoporosis. Our objective was to identify components similarly regulated in the pathology and have therapeutic potential by influencing crucial cellular processes in both bone and skeletal muscle.

Recent findings: The simultaneous decline in bone and muscle in osteosarcopenia involves a complex crosstalk between these tissues. Recent studies have uncovered several key mechanisms underlying this condition, including the disruption of cellular signaling pathways that regulate bone remodeling and muscle function and regeneration. Accordingly, emerging evidence reveals that dysregulation of microRNAs plays a significant role in the development of each of these hallmarks of osteosarcopenia. Although the recent recognition of osteosarcopenia as a single diagnosis of bone and muscle deterioration has provided new insights into the mechanisms of these underlying age-related diseases, several knowledge gaps have emerged, and a deeper understanding of the role of common microRNAs is still required. In this study, we summarize current evidence on the roles of microRNAs in the pathogenesis of osteosarcopenia and identify potential microRNA targets for treating this condition. Among these, microRNAs-29b and -128 are upregulated in the disease and exert adverse effects by inhibiting IGF-1 and SIRT1, making them potential targets for developing inhibitors of their activity. MicroRNA-21 is closely associated with the occurrence of muscle and bone loss. Conversely, microRNA-199b is downregulated in the disease, and its reduced activity may be related to increased myostatin and GSK3β activity, presenting it as a target for developing analogues that restore its function. Finally, microRNA-672 stands out for its ability to protect skeletal muscle and bone when expressed in the disease, highlighting its potential as a possible therapy for osteosarcopenia.

Purpose of review: This review is a critical analysis of treatment results obtained in clinical trials conducted in patients with chronic kidney disease (CKD) and secondary hyperparathyroidism (SHPT), hyperphosphatemia, or both.

Recent findings: Patients with CKD have a high mortality rate. The disorder of mineral and bone metabolism (CKD-MBD), which is commonly present in these patients, is associated with adverse outcomes, including cardiovascular events and mortality. Clinical trials aimed at improving these outcomes by modifying CKD-MBD associated factors have most often resulted in disappointing results. The complexity of CKD-MBD, where many players are closely interconnected, might explain these negative findings. We first present an historical perspective of current knowledge in the field of CKD-MBD and then examine potential flaws of past and ongoing clinical trials targeting SHPT and hyperphosphatemia respectively in patients with CKD.

Purpose of review: This review paper provides step-by-step instructions on the fundamental process, from handling fastq datasets to illustrating plots and drawing trajectories.

Recent findings: The number of studies using single-cell RNA-seq (scRNA-seq) is increasing. scRNA-seq revealed the heterogeneity or diversity of the cellular populations. scRNA-seq also provides insight into the interactions between different cell types. User-friendly scRNA-seq packages for ligand-receptor interactions and trajectory analyses are available. In skeletal biology, osteoclast differentiation, fracture healing, ectopic ossification, human bone development, and the bone marrow niche have been examined using scRNA-seq. scRNA-seq data analysis tools are still being developed, even at the fundamental step of dataset integration. However, updating the latest information is difficult for many researchers. Investigators and reviewers must share their knowledge of in silico scRNA-seq for better biological interpretation. This review article aims to provide a useful guide for complex analytical processes in single-cell RNA-seq data analysis.

Purpose of review: This review summarizes the recently published scientific evidence regarding the role of efferocytosis in bone dynamics and skeletal health.

Recent findings: Several types of efferocytes have been identified within the skeleton, with macrophages being the most extensively studied. Efferocytosis is not merely a 'clean-up' process vital for maintaining skeletal homeostasis; it also plays a crucial role in promoting resolution pathways and orchestrating bone dynamics, such as osteoblast-osteoclast coupling during bone remodeling. Impaired efferocytosis has been associated with aging-related bone loss and various skeletal pathologies, including osteoporosis, osteoarthritis, rheumatoid arthritis, and metastatic bone diseases. Accordingly, emerging evidence suggests that targeting efferocytic mechanisms has the potential to alleviate these conditions. While efferocytosis remains underexplored in the skeleton, recent discoveries have shed light on its pivotal role in bone dynamics, with important implications for skeletal health and pathology. However, there are several knowledge gaps and persisting technical limitations that must be addressed to fully unveil the contributions of efferocytosis in bone.

Purpose of review: Quantification of the morphology of osteocyte lacunae has become a powerful tool to investigate bone metabolism, pathologies and aging. This review will provide a brief overview of 2D and 3D imaging methods for the determination of lacunar shape, orientation, density, and volume. Deviations between 2D-based and 3D-based lacunar volume estimations are often not sufficiently addressed and may give rise to contradictory findings. Thus, the systematic error arising from 2D-based estimations of lacunar volume will be discussed, and an alternative calculation proposed. Further, standardized morphological parameters and best practices for sampling and segmentation are suggested.

Recent findings: We quantified the errors in reported estimation methods of lacunar volume based on 2D cross-sections, which increase with variations in lacunar orientation and histological cutting plane. The estimations of lacunar volume based on common practice in 2D imaging methods resulted in an underestimation of lacunar volume of up to 85% compared to actual lacunar volume in an artificial dataset. For a representative estimation of lacunar size and morphology based on 2D images, at least 400 lacunae should be assessed per sample.

Purpose of review: Beyond aging, senescent cells accumulate during multiple pathological conditions, including chemotherapy, radiation, glucocorticoids, obesity, and diabetes, even earlier in life. Therefore, cellular senescence represents a unifying pathogenic mechanism driving skeletal and metabolic disorders. However, whether senescent bone marrow adipocytes (BMAds) are causal in mediating skeletal dysfunction has only recently been evaluated.

Recent findings: Despite evidence of BMAd senescence following glucocorticoid therapy, additional evidence for BMAd senescence in other conditions has thus far been limited. Because the study of BMAds presents unique challenges making these cells difficult to isolate and image, here we review issues and approaches to overcome such challenges, and present advancements in isolation and histological techniques that may help with the future study of senescent BMAds. Further insights into the roles of BMAd senescence in the pathogenesis of skeletal dysfunction may have important basic science and clinical implications for human physiology and disease.

Purpose of the review: In this review, we discuss the most recent scientific advances on the reciprocal regulatory interactions between the skeletal and hematopoietic stem cell niche, focusing on immunomodulation and its interplay with the cell's mitochondrial function, and how this impacts osteoimmune health during aging and disease.

Recent findings: Osteoimmunology investigates interactions between cells that make up the skeletal stem cell niche and immune system. Much work has investigated the complexity of the bone marrow microenvironment with respect to the skeletal and hematopoietic stem cells that regulate skeletal formation and immune health respectively. It has now become clear that these cellular components cooperate to maintain homeostasis and that dysfunction in their interaction can lead to aging and disease. Having a deeper, mechanistic appreciation for osteoimmune regulation will lead to better research perspective and therapeutics with the potential to improve the aging process, skeletal and hematologic regeneration, and disease targeting.