Current Osteoporosis Reports最新文献

Purpose of review: To describe the contributions of osteocytes to the lesions in Paget's disease, which are characterized by locally overactive bone resorption and formation.

Recent findings: Osteocytes, the most abundant cells in bone, are altered in Paget's disease lesions, displaying increased size, decreased canalicular length, incomplete differentiation, and less sclerostin expression compared to controls in both patients and mouse models. Pagetic lesions show increased senescent osteocytes that express RANK ligand, which drives osteoclastic bone resorption. Abnormal osteoclasts in Paget's disease secrete abundant IGF1, which enhances osteocyte senescence, contributing to lesion formation. Recent data suggest that osteocytes contribute to lesion formation in Paget's disease by responding to high local IGF1 released from abnormal osteoclasts. Here we describe the characteristics of osteocytes in Paget's disease and their role in bone lesion formation based on recent results with mouse models and supported by patient data.

Purpose of review: The objective of this review is to summarize the literature on the prevalence and diagnosis of obesity and its metabolic profile, including bone metabolism, focusing on the main inflammatory and turnover bone mediators that better characterize metabolically healthy obesity phenotype, and to summarize the therapeutic interventions for obesity with their effects on bone health.

Recent findings: Osteoporosis and fracture risk not only increase with age and menopause but also with metabolic diseases, such as diabetes mellitus. Thus, patients with high BMI may have a higher bone fragility and fracture risk. However, some obese individuals with healthy metabolic profiles seem to be less at risk of bone fracture. Obesity has become an alarming disease with growing prevalence and multiple metabolic comorbidities, resulting in a significant burden on healthcare and increased mortality. The imbalance between increased food ingestion and decreased energy expenditure leads to pathological adipose tissue distribution and function, with increased secretion of proinflammatory markers and harmful consequences for body tissues, including bone tissue. However, some obese individuals seem to have a healthy metabolic profile and may not develop cardiometabolic disease during their lives. This healthy metabolic profile also benefits bone turnover and is associated with lower fracture risk.

Purpose of review: In this review, we summarize the current evidence that suggests that neutrophils play a key role in facilitating damage to local bone structures.

Recent findings: Neutrophil infiltration is a hallmark of inflammatory bone diseases such as rheumatoid arthritis (RA) and periodontitis disease (PD). Both of these human diseases are marked by an imbalance in bone homeostasis, favoring the degradation of local bone which ultimately leads to erosions. Osteoclasts, a multinucleated resident bone cell, are responsible for facilitating the turnover of bone and the bone damage observed in these diseases. The involvement of neutrophils and neutrophil extracellular trap formation have recently been implicated in exacerbating osteoclast function through direct and indirect mechanisms. We highlight a recent finding that NET proteins such as histones and elastase can generate non-canonical, inflammatory osteoclasts, and this process is mediated by post-translational modifications such as citrullination and carbamylation, both of which act as autoantigens in RA. It appears that NETs, autoantibodies, modified proteins, cytokines, and osteoclasts all ultimately contribute to local and permanent bone damage in RA and PD. However, more studies are needed to fully understand the role of neutrophils in inflammatory bone diseases.

Purpose of review: Despite advances in orthopedics, there remains a need for therapeutics to hasten fracture healing. However, little focus is given to the role the nervous system plays in regulating fracture healing. This paucity of information has led to an incomplete understanding of fracture healing and has limited the development of fracture therapies that integrate the importance of the nervous system. This review seeks to illuminate the integral roles that the nervous system plays in fracture healing.

Recent findings: Preclinical studies explored several methodologies for ablating peripheral nerves to demonstrate ablation-induced deficits in fracture healing. Conversely, activation of peripheral nerves via the use of dorsal root ganglion electrical stimulation enhanced fracture healing via calcitonin gene related peptide (CGRP). Investigations into TLR-4, TrkB agonists, and nerve growth factor (NGF) expression provide valuable insights into molecular pathways influencing bone mesenchymal stem cells and fracture repair. Finally, there is continued research into the connections between pain and fracture healing with findings suggesting that anti-NGF may be able to block pain without affecting healing. This review underscores the critical roles of the central nervous system (CNS), peripheral nervous system (PNS), and autonomic nervous system (ANS) in fracture healing, emphasizing their influence on bone cells, neuropeptide release, and endochondral ossification. The use of TBI models contributes to understanding neural regulation, though the complex influence of TBI on fracture healing requires further exploration. The review concludes by addressing the neural connection to fracture pain. 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 review: The traditionally understated role of neural regulation in fracture healing is gaining prominence, as recent findings underscore the peripheral nervous system's critical contribution to bone repair. Indeed, it is becoming more evident that the nervous system modulates every stage of fracture healing, from the onset of inflammation to repair and eventual remodeling.

Recent findings: Essential to this process are neurotrophins and neuropeptides, such as substance P, calcitonin gene-related peptide, and neuropeptide Y. These molecules fulfill key roles in promoting osteogenesis, influencing inflammation, and mediating pain. The sympathetic nervous system also plays an important role in the healing process: while local sympathectomies may improve fracture healing, systemic sympathetic denervation impairs fracture healing. Furthermore, chronic activation of the sympathetic nervous system, often triggered by stress, is a potential impediment to effective fracture healing, marking an important area for further investigation. The potential to manipulate aspects of the nervous system offers promising therapeutic possibilities for improving outcomes in fracture healing. 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 review: Musculoskeletal imaging serves a critical role in clinical care and orthopaedic research. Image-based modeling is also gaining traction as a useful tool in understanding skeletal morphology and mechanics. However, there are fewer studies on advanced imaging and modeling in pediatric populations. The purpose of this review is to provide an overview of recent literature on skeletal imaging modalities and modeling techniques with a special emphasis on current and future uses in pediatric research and clinical care.

Recent findings: While many principles of imaging and 3D modeling are relevant across the lifespan, there are special considerations for pediatric musculoskeletal imaging and fewer studies of 3D skeletal modeling in pediatric populations. Improved understanding of bone morphology and growth during childhood in healthy and pathologic patients may provide new insight into the pathophysiology of pediatric-onset skeletal diseases and the biomechanics of bone development. Clinical translation of 3D modeling tools developed in orthopaedic research is limited by the requirement for manual image segmentation and the resources needed for segmentation, modeling, and analysis. This paper highlights the current and future uses of common musculoskeletal imaging modalities and 3D modeling techniques in pediatric orthopaedic clinical care and research.

Purpose of review: SARS-CoV-2 infection, the culprit of the COVID-19 pandemic, has been associated with significant long-term effects on various organ systems, including bone health. This review explores the current understanding of the impacts of SARS-CoV-2 infection on bone health and its potential long-term consequences.

Recent findings: As part of the post-acute sequelae of SARS-CoV-2 infection, bone health changes are affected by COVID-19 both directly and indirectly, with multiple potential mechanisms and risk factors involved. In vitro and preclinical studies suggest that SARS-CoV-2 may directly infect bone marrow cells, leading to alterations in bone structure and osteoclast numbers. The virus can also trigger a robust inflammatory response, often referred to as a "cytokine storm", which can stimulate osteoclast activity and contribute to bone loss. Clinical evidence suggests that SARS-CoV-2 may lead to hypocalcemia, altered bone turnover markers, and a high prevalence of vertebral fractures. Furthermore, disease severity has been correlated with a decrease in bone mineral density. Indirect effects of SARS-CoV-2 on bone health, mediated through muscle weakness, mechanical unloading, nutritional deficiencies, and corticosteroid use, also contribute to the long-term consequences. The interplay of concurrent conditions such as diabetes, obesity, and kidney dysfunction with SARS-CoV-2 infection further complicates the disease's impact on bone health. SARS-CoV-2 infection directly and indirectly affects bone health, leading to potential long-term consequences. 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 review: This Comment represents three review articles on the relationship between Alzheimer's disease, osteoporosis, and fracture in an exploration of the benefits that AI can provide in scientific writing. The first drafts of the articles were written (1) entirely by humans; (2) entirely by ChatGPT 4.0 (AI-only or AIO); and (3) by humans and ChatGPT 4.0 whereby humans selected literature references, but ChatGPT 4.0 completed the writing (AI-assisted or AIA). Importantly, each review article was edited and carefully checked for accuracy by all co-authors resulting in a final manuscript which was significantly different from the original draft.

Recent findings: The human-written article took the most time from start to finish, the AI-only article took the least time, and the AI-assisted article fell between the two. When comparing first drafts to final drafts, the AI-only and AI-assisted articles had higher percentages of different text than the human article. The AI-only paper had a higher percentage of incorrect references in the first draft than the AI-assisted paper. The first draft of the AI-assisted article had a higher similarity score than the other two articles when examined by plagiarism identification software. This writing experiment used time tracking, human editing, and comparison software to examine the benefits and risks of using AI to assist in scientific writing. It showed that while AI may reduce total writing time, hallucinations and plagiarism were prevalent issues with this method and human editing was still necessary to ensure accuracy.

Purpose of review: This review examines the linked pathophysiology of Alzheimer's disease/related dementia (AD/ADRD) and bone disorders like osteoporosis. The emphasis is on "inflammaging"-a low-level inflammation common to both, and its implications in an aging population.

Recent findings: Aging intensifies both ADRD and bone deterioration. Notably, ADRD patients have a heightened fracture risk, impacting morbidity and mortality, though it is uncertain if fractures worsen ADRD. Therapeutically, agents targeting inflammation pathways, especially Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) and TNF-α, appear beneficial for both conditions. Additionally, treatments like Sirtuin 1 (SIRT-1), known for anti-inflammatory and neuroprotective properties, are gaining attention. The interconnectedness of AD/ADRD and bone health necessitates a unified treatment approach. By addressing shared mechanisms, we can potentially transform therapeutic strategies, enriching our understanding and refining care in our aging society. 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 review: The purpose of this review is to highlight the evidence of microvascular dysfunction in bone and marrow and its relation to poor skeletal outcomes in diabetes mellitus.

Recent findings: Diabetes mellitus is characterized by chronic hyperglycemia, which may lead to microangiopathy and macroangiopathy. Micro- and macroangiopathy have been diagnosed in Type 1 and Type 2 diabetes, coinciding with osteopenia, osteoporosis, enhanced fracture risk and delayed fracture healing. Microangiopathy has been reported in the skeleton, correlating with reduced blood flow and perfusion, vasomotor dysfunction, microvascular rarefaction, reduced angiogenic capabilities, and augmented vascular permeability. Microangiopathy within the skeleton may be detrimental to bone and manifest as, among other clinical abnormalities, reduced mass, enhanced fracture risk, and delayed fracture healing. More investigations are required to elucidate the various mechanisms by which diabetic microvascular dysfunction impacts the skeleton.