Current Osteoporosis Reports最新文献

Purpose of review: We evaluate the converging evidence positioning lithium as a systemic modulator of bone and brain health through shared molecular pathways. This review examines the molecular basis, preclinical data, and clinical observations suggesting that lithium-long established as first-line therapy for bipolar disorder-may simultaneously protect against osteoporosis and neurodegeneration as two clinical conditions increasingly recognized to share biological substrates.

Recent findings: Lithium inhibits glycogen synthase kinase-3β (GSK-3β), stabilizes β-catenin, and activates Wnt signaling in neurons and osteoblasts, while also modulating calcium-inositol homeostasis and suppressing NF-κB-mediated inflammation. Large observational studies report lower dementia incidence and reduced fracture risk in long-term lithium users, together with increases in bone mineral density. Declining brain lithium concentrations in patients with Alzheimer's disease raise the hypothesis that lithium may act as an essential micronutrient rather than solely a pharmacological agent. Bidirectional brain-bone crosstalk involving osteocalcin signaling and sclerostin transport across the blood-brain barrier provides a mechanistic basis for these pleiotropic effects. Lithium offers a unique paradigm for understanding and potentially treating age-related decline in multiple organ systems at subclinical dosage and concentration. However, observational study limitations, optimal dose uncertainties, and toxicity related to long-term usage concerns necessitate rigorous randomized controlled trials before broader clinical recommendations can be made. Future research should focus on optimizing formulation and patient selection to realize lithium's dual protective potential for bone and brain while minimizing risk.

Purpose of review: This review aims to highlight the emerging concept that nutrients and metabolites act not merely as energy sources or biosynthetic precursors, but also as instructive signalling molecules in osteoclasts. While much is known about transcriptional and genetic pathways governing osteoclast differentiation and function, comparatively little attention has been given to the role of cellular metabolism and nutrient-sensing mechanisms. This review seeks to categorise key metabolites based on their signalling roles and examine how they influence osteoclastogenesis through metabolic, epigenetic, and inflammatory pathways.

Recent findings: Recent studies have demonstrated that nutrients such as glucose, amino acids, and lipids, along with their intermediary metabolites such as succinate, itaconate, α-ketoglutarate (αKG), S-adenosylmethionine (SAM), and acetyl-CoA, regulate osteoclast formation and function by modulating signalling cascades and epigenetic landscapes. These molecules engage nutrient sensors (e.g., aldolase, mTORC1, CPT1) and transcriptional regulators (e.g., NFATc1, PPARs), while also affecting chromatin structure, inflammatory responses, and organelle dynamics. Osteoclast metabolism is tightly linked to cellular fate through nutrient-sensing and metabolite-driven signalling. Elucidating these pathways will reshape our understanding of osteoclast regulation and help identify new metabolic targets for treating bone diseases.

Purpose of review: This review article summarizes progress made using transcriptomics, in particular RNA-seq studies such as bulk, single cell (sc) and spatial sequencing results, in the study of bone and cartilage in the context of osteoarthritis (OA) and osteoporosis (OP) over the past two years.

Recent findings: Recent advances in OA and OP research using advanced transcriptomics technologies have been crucial in the identification of cellular and molecular patterns of disease, facilitating a deeper knowledge of disease endotypes, mechanisms, and putative therapeutic targets. Increased use of public data repositories for hypothesis building and validation studies is an emerging theme in transcriptomics research, emphasizing the usefulness of growing transcriptomics databases to the research community. Due to unique challenges associated with bone and cartilage, it has been relatively difficult to deploy spatial sequencing in these tissues, however effective protocols for spatial sequencing have emerged, unlocking new potential for discovery.

Purpose of review: Spatial transcriptomics enables to capture the whole transcriptome within the local microenvironment in bone. Within this review, we provide an overview of recent spatial transcriptomics applications and indicate its potential for advancing basic and translational research in skeletal development and maintenance, bone-related disorders, as well as fracture healing.

Recent findings: Recent developments in sample preparation protocols have enabled the application of spatial transcriptomics to bone. However, there is a lack of standardized data analyses pipelines for spatial transcriptomics in bone. The interpretability of current data sets further suffers from low sample sizes. We consider spatial transcriptomics a cornerstone technology for unravelling bone's spatial and molecular complexity. Via integration into emerging multi-omics and multi-modal imaging approaches, spatial transcriptomics has the potential to advance translational-targeted research in the fields of orthopaedics and musculoskeletal research.

Purpose of review: This review evaluates established risk factors, examines pathogenic mechanisms, determines optimal treatment durations, and proposes evidence-based management strategies for Osteoporosis to enhance clinical practice.

Recent findings: Key risk factors include advanced age, Asian descent, prolonged Bisphosphonates therapy (exceeding 5 years for alendronate or 3 years for zoledronic acid) without drug holidays, and distinct femoral geometry. The underlying pathophysiology is primarily linked to excessive suppression of bone turnover, resulting in progressive microdamage accumulation. Current clinical guidelines suggest implementing Bisphosphonates treatment interruptions (1-3 years for oral regimens; 3-5 years for intravenous administration) in patients with moderate fracture risk (femoral neck T-score > -2.5). Importantly, denosumab withdrawal necessitates a transition to alternative therapies-typically Bisphosphonates or teriparatide-to mitigate rebound bone loss. For managing Atypical Femoral Fractures, teriparatide demonstrates efficacy in promoting healing of active lesions, whereas intramedullary nailing represents the gold standard for complete fractures or high-risk incomplete fractures. Atypical Femoral Fractures management requires balancing Anti-Resorptive benefits against risks via individualized treatment, timely drug holidays, and rapid transition to bone-forming agents post-denosumab. Prophylactic surgery benefits high-risk fractures. Future research should elucidate denosumab's mechanisms and develop targeted therapies.

Purpose of review: This review synthesizes the recently published scientific evidence on sociodemographic (age-, sex-, race/ethnicity-, or income/insurance-based) differences in epidemiology and management of osteoporosis-related vertebral fractures.

Recent findings: We identified 23 studies that investigated and reported on the presence of age-, sex-, race/ethnicity-, insurance, and income-based differences in the epidemiology and management of osteoporosis-related vertebral fractures. These fractures are generally more common in older adults and less common in Black adults compared to White adults. Vertebral augmentation is sometimes used in the treatment of osteoporosis-related vertebral fractures and has been shown to be less common in racial and ethnic minorities. Reported sociodemographic differences in the epidemiology and management of osteoporosis-related vertebral fractures are not consistent across studies. However, comparatively few studies have investigated causes of these differences, which are important for determining whether the differences represent true disparities in care, and consequently inform interventions that could reduce those disparities. Age-, sex-, race/ethnicity- insurance, and income-based differences in the epidemiology and management of osteoporosis-related vertebral fractures exist. Further work is needed to understand the underlying causes of these differences so that interventions can be developed to address them.

Purpose of review: In this review, we describe the interaction between B cells and bone during development, aging, and disease.  RECENT FINDINGS: There is an increased interest in identifying the mechanisms of interaction between immune cells and the skeletal system. This knowledge is critical for understanding the pathology of autoimmune diseases and developing therapeutic interventions. Humoral immunity depends on B cells and their secreted immunoglobulin (antibodies). Earlier studies described B cell influence on the skeletal system, with a major focus on the role of plasma cells and secreted antibodies. The contribution of bone marrow developing B cells to the skeletal system was still poorly studied and represents a gap in our knowledge. This is an active area of investigation in our research group. The crosstalk between B cells and bone starts as early as the commitment of hematopoietic stem cells to the B cell lineage and the differentiation of mesenchymal stem cells to osteoblast progenitors. This crosstalk is active during different developmental stages and continues throughout the life of the individual, especially since both B cells and bone cells share the same developmental niche. Bi-directional interaction of developing B cells and osteoblasts, osteoclasts, and chondroblasts ensures their normal development and functional activity. During aging, this interaction is disrupted, leading to disease progression, decreased bone mass, and osteoporosis. A better understanding of B cell-bone interactions will help identify novel immune targets that might provide therapeutic benefit for the elderly and patients.

Purpose of review: Proximal humerus fractures are common osteoporosis-related fractures in the elderly population. Due to these fractures, the quality of life of patients decreases significantly. This review aims to (1) describe the epidemiology of osteoporosis-related proximal humerus fractures, (2) evaluate the current management of these fractures, and (3) address the economic burden of these fractures.

Recent findings: Recent studies highlight that the incidence of proximal humerus fractures due to osteoporosis is increasing due to the increase in the elderly population. There are many methods in the literature for the treatment of these fractures, including nonsurgical treatment, minimally invasive surgery, open reduction internal fixation, intramedullary nailing and arthroplasty. Reverse shoulder arthroplasty is gaining popularity for the treatment of osteoporosis-related comminuted and displaced proximal humerus fractures in the elderly population. Post-treatment rehabilitation is as critical as the treatment itself. Osteoporosis-related proximal humeral fractures pose a serious problem in the elderly population. Multiple treatment options are available, and there is no consensus in the literature regarding treatment and rehabilitation protocols. The characteristics of the patient and the fracture should be evaluated together, and the appropriate treatment and rehabilitation protocol should be determined accordingly. Future studies should aim to standardize treatment and rehabilitation protocols and alleviate the economic burden caused by these fractures.