Bone homeostasis, along with the processes of bone formation and resorption, is tightly regulated. Moving beyond the traditional focus on endocrine factors, osteoimmunology examines the influence of immune factors on skeletal homeostasis. While previous research has primarily focused on how T cells promote osteoclast proliferation and differentiation, the mechanisms by which T cells regulate osteoblasts remain comparatively understudied. In this review, we provide a comprehensive summary of how major T-cell subsets and their key cytokines regulate osteoblasts. We also discuss the mechanisms and therapeutic potential of the four-axial network across a range of skeletal disorders—including postmenopausal osteoporosis, rheumatoid arthritis, and fractures—with the aim of offering new perspectives for clinical management. These regulatory functions do not operate in isolation; rather, they act in concert to form an integrated functional network. Under pathological conditions, the classical Th1/Th2 and Th17/Treg axes can shift toward a pathogenic Th1/Th17 synergistic axis and a protective Th2/Treg synergistic axis, underscoring that disease pathogenesis often involves multiple cell types acting in concert. By focusing on the balance among T-cell subsets and elaborating on their synergistic effects through four core axes, this review provides a conceptual framework for understanding immune regulation of osteoblasts. Targeting the imbalance among T-cell subsets may therefore offer novel strategies for the treatment of skeletal disorders.
Osteosarcopenia—osteoporosis co-occurring with sarcopenia—has a pooled prevalence of 18.5
Here, we explore how the osteoclast’s many nuclei inform behavior, set activity, and underpin osteoclast-driven pathologies. Over the last decade, new discoveries have demonstrated that osteoclast multinucleation is a major determinant of activity and driver of pathologic behavior. We open with a review of postnatal skeletal maintenance and the role osteoclasts play in coordinating the multicellular unit responsible for life-long skeletal development. Then, we focus the second half on recent developments in the understanding of how multinucleation influences osteoclast resorptive behavior, underpins skeletal pathology, and close with a discussion on the fate and nature of these syncytial cells. Much of this latter discussion is stimulated by recent observations focusing on the behavior and fate of individual osteoclasts as compared to previous systemic measurements of their activity. In the end, work over the last decade - in particular, fate tracing, advances in the live imaging of osteoclast activity, and mechanistic observations of syncytial fission - pushes us to consider the possibility that osteoclasts are more than individual cells but instead operate as community of individuals held in a common boarder. It seems to us that Evolution, when faced with a task too great for one, answered with many - A Syncytial Community.
Individuals living with overweight or obesity have a higher bone mineral density, however bone quality may be compromised, leading to an increased susceptibility to fractures and impaired skeletal integrity. Nutrition is a potentially modifiable factor that may influence both body weight and bone metabolism through effects on inflammation, body composition, and metabolic regulation. In particular, dietary quality indices such as the Healthy Eating Index (HEI) provide a comprehensive assessment of adherence to dietary guidelines and may offer insight into how overall eating patterns influence bone quality among individuals with excess body weight. In this review, we have summarized the impact of dietary quality using the HEI on bone health in individuals who are living with overweight or obesity. Recent studies show a positive relationship of high HEI with bone parameters in overweight and obese individuals. Specifically, studies report on a higher Trabecular bone score (TBS), lumbar and femoral neck BMD, lower osteoporosis risk and higher serum 25 hydroxy vitamin D levels in populations with a higher HEI. Currently studies assessing impact of HEI on bone health in obesity are cross sectional in nature. Future studies should assess the impact of increasing HEI on bone health in a prospective design and the impact of weight loss and increasing HEI on bone quality in individuals living with overweight and obesity.
Implementation of falls prevention programs at scale remains challenging due to resource constraints, clinic dependency and inequitable access. We critically review digital health technologies and map these to the World Falls Guidelines (WFG) risk-stratified pathway, from risk screening to intervention delivery, appraising the evidence, clinical readiness and implementation challenges. Self-managed digital exercise programs have the strongest evidence base, with three trials demonstrating reductions in falls among community-living older people and economic data supporting cost-effectiveness in those with a history of falls. Other technologies demonstrate feasibility, but none has demonstrated falls reduction in adequately powered trials. Implementation evidence is emerging but concentrated in high-income, digitally literate populations. Mapped to the WFG pathway, digital exercise programs are ready for routine implementation; realising broader potential requires regulatory frameworks that set evidence standards for digital products, funding models that support digital care and sustained commitment to equitable access across the diversity of older people.
