Bone metabolism is a dynamic physiological process that relies on the precise balance between bone formation and resorption to maintain bone homeostasis, in which innate immune cells play an indispensable role. Innate immune cells interact directly or indirectly with bone cells, participating in the regulation of inflammatory and immune processes and affecting bone metabolism balance. This article aims to clarify the mechanisms by which innate immune cells regulate bone metabolism, thus providing new insights for the prevention and treatment of bone metabolic disorders.

Osteoarthritis (OA) is a whole-joint disease involving cartilage, synovium, subchondral bone, and neurovascular structures. Synovitis, damage-associated molecular patterns, and interactions between macrophages and fibroblast-like synoviocytes have been widely studied. However, a tissue-level explanation is still lacking for how low-grade and fluctuating synovial responses become persistent inflammation. We therefore propose a framework of synovial immune control failure. In this framework, the synovium does more than participate in inflammation. By clearing intra-articular damage-related material, limiting the duration of inflammation, maintaining stromal homeostasis, and regulating the entry of peripheral immune cells, it helps determine whether local joint inflammation can return to a low-level state. When damage-related inputs persist and debris clearance, inflammatory resolution, and resetting of cellular states do not occur in parallel, macrophages, fibroblast-like synoviocytes, and the vascular-interstitial interface may form a mutually sustaining pathological cellular network. Disease-associated cellular states and their interactions may then be retained locally in the synovium, forming what this article defines as an inflammatory niche. This niche may form bidirectional feedback with cartilage degeneration and subchondral bone remodeling. However, the synovium is not the common initiating tissue in all patients with OA. This framework may be most relevant to disease subtypes with persistent or recurrent synovitis, myeloid cell activation, and abnormal stromal remodeling. We further discuss the evidence base, boundaries, testable predictions, and potential implications of this model for OA patient stratification and synovium-targeted intervention.

Cervical spine degeneration is frequently accompanied by long-term alterations in the hemodynamic environment of the vertebral arteries. Traditionally, vascular abnormalities associated with cervical degeneration have been interpreted mainly from the perspectives of structural compression or macroscopic hemodynamic disturbance. However, these explanations do not fully account for the functional instability of posterior circulation perfusion that may occur even in the absence of overt arterial stenosis. Emerging evidence suggests that endothelial senescence represents a central biological process linking chronic mechanical stress, disturbed flow patterns, and progressive vascular dysfunction. In the vertebral artery, which is anatomically coupled to the cervical spine and exposed to dynamic biomechanical forces, long-term alterations in vascular geometry and shear stress may gradually reshape the local microenvironment of the vascular wall. These changes can promote endothelial stress responses, metabolic imbalance, and inflammatory signaling, ultimately facilitating the development of endothelial senescence.In this review, we integrate current knowledge from vascular biology, mechanobiology, and cerebrovascular physiology to examine how cervical degenerative changes may remodel the vertebral artery microenvironment. We discuss the molecular basis of endothelial senescence, the role of disturbed flow in activating pro-senescent signaling pathways, and the potential consequences of endothelial aging for the functional stability of the posterior circulation. By framing vertebral artery–related abnormalities within the context of endothelial senescence and vascular microenvironment remodeling, this perspective provides a conceptual framework that may help explain chronic posterior circulation vulnerability associated with cervical degeneration and identify potential directions for future mechanistic and translational research.

Background:Osteoporosis and bone density reduction are significant health concerns in elderly populations. While aging is a primary factor, drug-induced bone loss-particularly associated with antiviral agents, proton pump inhibitors (PPIs), and immunomodulatory drugs-has become a growing issue in patients managing multiple conditions. Objective:This study aims to comprehensively assess adverse drug reactions (ADRs) related to bone density reduction and osteoporosis in elderly patients using the FDA Adverse Event Reporting System (FAERS). A specific focus is placed on HIV patients using antiretroviral therapy (ART), alongside an exploration of gender differences and toxicological mechanisms of high-risk drugs. Methods:Data from FAERS (2004-Q2 2025) were analyzed using disproportionality analysis (DPA) to calculate Reporting Odds Ratios (RORs) and 95% confidence intervals (CIs). Toxicological analysis was conducted on high-risk drugs (e.g., Tenofovir Disoproxil) using PubChem, GeneCards, and GO/KEGG pathway enrichment to identify disrupted biological processes. Results:Antiretroviral drugs exhibited the most significant risk signals. For decreased bone density, Emtricitabine/Tenofovir Disoproxil (ROR = 713.48, 95% CI: 648.66-784.79) and Tenofovir Disoproxil (ROR = 665.79, 95% CI: 611.91-724.42) showed extreme associations. For osteoporosis, significant signals were also identified for these antivirals, as well as for Esomeprazole (ROR = 12.23, 95% CI: 11.27-13.28) and Adalimumab (ROR = 2.16, 95% CI: 1.99-2.35). Gender-specific differences indicated men are at higher risk from antiviral drugs, whereas women are more affected by bone metabolic and immunomodulatory regulators. Toxicological analyses suggest these drugs disrupt vitamin D metabolism, calcium homeostasis, and parathyroid hormone (PTH) signaling. Conclusion:Long-term use of antiretroviral drugs, PPIs, and immunomodulators is strongly linked to bone metabolic disorders in the elderly. Although pharmacovigilance studies utilizing FAERS are limited by spontaneous reporting bias and the inability to establish direct causality, these quantitative findings and toxicological insights provide robust real-world evidence for enhancing clinical monitoring and personalized risk management.

The sustained progression of osteoarthritis (OA) arises not only from mechanical injury and inflammatory stimulation but also from the gradual loss of chondrocyte homeostatic identity. However, a unifying mechanism explaining how metabolic abnormalities within the joint microenvironment are converted into relatively stable degenerative programs remains lacking. The discovery of lactylation provides a new perspective on this question. OA-associated hypoxia, inflammation, and aberrant mechanical loading can promote glycolytic reprogramming and lactate accumulation, while lactate further channels metabolic stress into chromatin regulation and protein functional networks through histone and non-histone lactylation. Current evidence suggests that this process does not merely amplify a single catabolic pathway, but reshapes chondrocyte fate at multiple levels by impairing matrix-maintaining capacity, driving the transition from a homeostatic phenotype toward catabolic, fibrotic, and senescent states, and altering cellular susceptibility to oxidative injury and pathological cell death. Meanwhile, metabolic reprogramming in synovial cells and immune cells may expand the intra-articular lactate pool, thereby linking intracellular lactylation changes with inter-tissue inflammatory crosstalk. Notably, the effects of lactylation are not uniformly pathogenic, but depend on the modified site, protein substrate, cellular state, redox environment, and disease stage. This bidirectionality is evident in both histone and non-histone lactylation: UGDH K6 lactylation and selected H3K18la-associated programs are linked to matrix damage and fibrotic phenotypes, whereas H3K56la may preserve COL2A1 expression and enhance chondrocyte stress adaptation under specific post-traumatic and redox conditions. Lactylation is therefore better understood as a metabolic state-driven “fate code” rather than a passive marker of lactate accumulation. This review integrates the continuum linking lactate metabolism, site-specific lactylation, and chondrocyte fate remodeling, with particular emphasis on matrix homeostasis, cellular senescence, survival–death transitions, and the inflammatory microenvironment. It also discusses the therapeutic implications of shifting from global modulation of lactylation toward cell- and site-specific intervention. This framework may deepen our understanding of OA chronicity and provide a theoretical basis for metabolic phenotype stratification and disease-modifying therapy.

Osteoporosis is a systemic skeletal disorder traditionally attributed to imbalances in bone metabolism. Increasing evidence suggests that the intestinal environment and chronic inflammation play important roles in itspathogenesis. The gut–bone–inflammation axis provides a novel perspective for understanding the interactions among intestinal barrier function, immune regulation, and bone homeostasis. This review aims to summarize current evidence regarding the role of intestinal barrier disruption in osteoporosis and to discuss its contribution within the framework of the gut–bone–inflammation axis. Relevant experimental and clinical studies from the existing literature were reviewed and synthesized, with a focus on intestinal barrier integrity, gut microbiota dysbiosis, inflammatory mediators, immune activation, and bone metabolism. Disruption of the intestinal barrier increases intestinal permeability, facilitating the translocation of microbial products and pro-inflammatory mediators into the systemic circulation. This process promotes chronic low-grade inflammation, enhances osteoclast differentiation and activity, suppresses osteoblast function, and disrupts the balance of bone remodeling. Gut microbiota imbalance, immune activation, and sustained inflammatory signaling collectively contribute to bone loss and structural deterioration in osteoporosis. Intestinal barrier dysfunction plays a pivotal role in osteoporosis through modulation of systemic inflammation and bone metabolism. Strategies aimed at preserving intestinal barrier integrity and regulating the gut microbiota may offer promising preventive and therapeutic approaches for the management of osteoporosis.

Ossification of the posterior longitudinal ligament (OPLL) is a degenerative spinal disorder characterized by heterotopic ossification of ligamentous tissue. Its pathogenesis is multifactorial and complex, involving genetic susceptibility, chronic inflammation, mechanical stress, and metabolic dysregulation. In recent years, accumulating evidence has demonstrated that angiogenesis not only supplies essential nutrients and metabolic support to ossified ligament regions but also actively regulates the differentiation of mesenchymal stem cells toward osteogenic and chondrogenic lineages through specific molecular signaling pathways, thereby promoting ectopic bone formation. Focusing on angiogenesis as a central theme, this review systematically summarizes the mechanisms by which key molecules, including LOXL2, Sema3A, integrin αVβ3, ANGPT2, IL-6, TGF-β, the ACE D/D polymorphism, and YAP, mediate the coupling of angiogenesis and osteogenesis in OPLL. Furthermore, we propose angiogenesis-targeted strategies as a potential therapeutic avenue for OPLL, aiming to provide new theoretical insights and directions for both basic research and clinical intervention.

Background The management of avulsion fractures of the lateral collateral ligament of the ankle is a topic of debate. However, with the increase in sports injuries, the incidence of these fractures has increased.This article describes a new modified double-row suture bridge technique for the treatment of avulsion fractures of the lateral collateral ligament of the ankle and evaluates its preliminary clinical results. Methods From 2021 to 2023, a total of 15 patients with avulsion fractures of the lateral ankle ligament were treated using a modified double-row suture bridge technique. The clinical outcomes of these patients were evaluated using objective data collected through clinical examinations.The following section contains the findings, radiologic evaluations including x-rays and computed tomography (CT) scans, and follow-up analyses using the American Orthopaedic Foot and Ankle Society ankle-foot (AOFAS) score, the Karlsson Ankle Function Score (KAFS), and Visual Analogue Scale (VAS). Preoperative and follow-up scores were compared by Student's t test. (p < 0.05). Results The mean age of the patients was 31.47 ± 7.56 years (range: 18–48). The mean follow-up time was 14.42 ± 1.51 months (range: 12–15).At final follow-up, the mean AOFAS score (P < 0.001) improved to 91.50 ± 2.65 points (range: 87–96), the mean KAFS score (P < 0.001) improved to 77.08 ± 3.97 points (range: 70–85), and Mean VAS score (p < 0.001) decreased to 0.25 ± 0.45 points (range: 0–1 points).Based on the AOFAS score, 13 patients had excellent results and 2 patients had good results. Follow-up imaging assessment showed satisfactory fracture alignment and all healed completely. Clinical examination showed good ankle mobility.At the last follow-up visit, the dorsiflexion range of motion of the ankle joint was 15–20 degrees, the plantar flexion range of motion was 43–45 degrees, the inversion range of motion was 28–34 degrees, and the eversion range of motion was 23–25 degrees. Conclusions The modified double-row suture bridge technique facilitates anatomical repositioning and effective fixation of lateral collateral ligament avulsion fractures of the ankle, thereby restoring the integrity of the lateral ankle ligament complex, and improves ankle function.This technique is simple to operate, with remarkable clinical effects, and is worthy of further promotion and use in the clinic.

Osteoarthritis (OA) is a degenerative joint disease influenced by multiple factors, with its etiology arising from intricate interactions among mechanical stress, inflammatory processes, and disruptions in bone metabolism. Recent research in bone immunology indicates that immune-mediated mechanisms significantly contribute to the progression of OA, highlighting the interactions among immune cells, cytokine networks, and bone components. Immune cells interact with osteoclasts, osteoblasts, and chondrocytes in a variety of ways. These interactions foster a pro-inflammatory microenvironment, contributing to cartilage breakdown, synovial inflammation, and the sclerosis of subchondral bone. In this article, we present a comprehensive review of bone immunology in OA, focusing on the critical role of immune cells and their cytokine-mediated feedback loops in the pathophysiology of OA. In addition, we are exploring novel therapeutic strategies targeting bone immune pathways, including macrophage polarization, T-cell differentiation, and stem cell therapy to restore the metabolic balance between immunity and bone. By integrating cutting-edge research in bone immunology, this review integrates the latest advancements in bone immunology to construct a comprehensive framework for unraveling the pathogenesis of OA, laying a theoretical foundation for the development of innovative precision therapies.

Bone homeostasis is a homeostasis process constructed by osteoblast bone formation and osteoclast bone resorption. Bone homeostasis imbalance and dysfunction are the basis for the development of various orthopedic diseases such as osteoporosis, osteoarthritis, and steroid-induced avascular necrosis of femoral head. Previous studies have demonstrated that ferroptosis can induce lipid peroxidation through the generation of reactive oxygen species, activate a number of signaling pathways, and participate in the regulation of osteoblast bone formation and osteoclast bone resorption, resulting in bone homeostasis imbalance, which is an important factor in the pathogenesis of many orthopedic diseases, but the mechanism of ferroptosis is still unknown. In recent years, it has been found that, in addition to iron metabolism and intracellular antioxidant system imbalance, organelle dysfunction is also a key factor affecting ferroptosis. This paper takes this as the starting point, reviews the latest literature reports at home and abroad, elaborates the pathogenesis and regulatory pathways of ferroptosis and the relationship between ferroptosis and various organelles, and summarizes the mechanism by which ferroptosis mediates bone homeostasis imbalance, with the aim of providing new directions for the research related to ferroptosis and new ideas for the prevention and treatment of bone and joint diseases.

Long non-coding RNA (LncRNA), with transcripts over 200 nucleotides in length, play critical roles in numerous biological functions and have emerged as significant players in the pathogenesis of osteoarthritis (OA), an inflammatory condition traditionally viewed as a degenerative joint disease. This review comprehensively examines the influence of LncRNA on the inflammatory processes driving OA progression, focusing on their role in regulating gene expression, cellular activities, and inflammatory pathways. Notably, LncRNAs such as MALAT1, H19, and HOTAIR are upregulated in OA and exacerbate the inflammatory milieu by modulating key signaling pathways like NF-κB, TGF-β/SMAD, and Wnt/β-catenin. Conversely, LncRNA like MEG3 and GAS5, which are downregulated in OA, show potential in dampening inflammatory responses and protecting against cartilage degradation by influencing miRNA interactions and cytokine production. By enhancing our understanding of LncRNA' roles in OA inflammation, we can better leverage them as potential biomarkers for the disease and develop innovative therapeutic strategies for OA management. This paper aims to delineate the mechanisms by which LncRNA influence inflammatory responses in OA and propose them as novel targets for therapeutic intervention.

The imbalance of bone metabolism and homeostasis in the femoral head caused by excessive use of glucocorticoids is one of the important mechanisms of hormone-induced femoral head necrosis. NLRP3 inflammasome, a key cytokine of pyrodeath, plays an important role in the SANFH mechanism. To clarify the structure, activation pathway and regulatory mechanism of the NLRP3 inflammasome, and the mechanism of NLRP3 inflammasome and downstream inflammatory factors IL-1β and IL-18 on osteoblasts, osteoclasts, and bone marrow mesenchymal stem cells in steroid-induced femoral head necrosis, may provide new ideas and targets for the prevention and treatment of steroid-induced femoral head necrosis. In this paper, the relevant mechanism of NLRP3 inflammasome in bone metabolism and homeostasis is reviewed. The specific mechanism of NLRP3 inflammasome in SANFH osteogenesis and osteoclast differentiation are systematically expounded. This may provide some references for clinical treatment and basic research.

Osteoclasts are the only cells in the human body with bone resorption function and play an irreplaceable role in the process of bone repair and reconstruction. In recent years, it has been found that iron accumulation is closely related to the proliferation and differentiation of osteoclasts, iron accumulation activates the downstream mitogen-activated protein kinase and nuclear factor-κB pathway by generating a large amount of reactive oxygen species, inducing the proliferation and differentiation of osteoclasts, thereby causing bone loss and weakening bone strength. In this paper, the relevant mechanisms of iron accumulation regulating the proliferation and differentiation of osteoclasts are reviewed.

激素性股骨头坏死(steroid-induced avas-cular necrosis of the femoral head,SANFH)是临床上常见的疑难杂症,其致残率高、预后差的特点,严重威胁了人类的健康.SANFH的发病机制十分复杂,但现在越来越多的研究表明,大量的糖皮质激素会导致骨组织细胞的线粒体功能异常,发生氧化应激、线粒体自噬、以及线粒体动力学改变,导致细胞受损或死亡,进而导致股骨头内骨代谢失衡、血流异常,加速了SANFH的发生发展.中药有着安全性高、副作用少等优点,在SANFH的治疗中有着良好的疗效.中药复方、单味中药和中药活性成分可以通过直接或间接地调控相应的信号通路中关键分子表达,多靶点改善线粒体功能,显著防治SANFH的发生发展,受到了学者们的广泛关注.该文综述了SANFH与线粒体功能之间的关系,以及中药通过调控线粒体功能来防治SANFH的作用机制,以期为临床应用中药调控线粒体功能来治疗SANFH提供一定的思路与方法.

本文旨在介绍手法治疗神经根型颈椎病(CSR)的中医理论依据、作用机制及临床疗效,分析认为手法治疗CSR疗效确切且优势突出,可纠正关节紊乱与错位、恢复颈椎生物力学平衡、调节局部血液循环,但目前仍存在循证证据等级低、疗效机制欠深入等问题.因此,在手法治疗CSR的临床及基础研究中,应以客观的解剖学知识、高质量循证依据、手法标准化、疗效作用机制研究为重点,重视手法操作的安全性、规范性、有效性,为评价及观察手法治疗疗效及作用机制提供可视化依据.

Bone homeostasis is a dynamic equilibrium state of bone formation and absorption, ensuring skeletal development and repair. Bone immunity encompasses all aspects of the intersection between the skeletal and immune systems, including various signaling pathways, cytokines, and the crosstalk between immune cells and bone cells under both homeostatic and pathological conditions. Therefore, as key cell types in bone immunity, macrophages can polarize into classical pro-inflammatory M1 macrophages and alternative anti-inflammatory M2 macrophages under the influence of the body environment, participating in the regulation of bone metabolism and playing various roles in bone homeostasis. M1 macrophages can not only act as precursors of osteoclasts (OCs), differentiate into mature OCs, but also secrete pro-inflammatory cytokines to promote bone resorption; while M2 macrophages secrete osteogenic factors, stimulating the differentiation and mineralization of osteoblast precursors and mesenchymal stem cells (MSCs), and subsequently increase bone formation. Once the polarization of macrophages is imbalanced, the resulting immune dysregulation will cause inflammatory stimulation, and release a large amount of inflammatory factors affecting bone metabolism, leading to pathological conditions such as osteoporosis (OP), rheumatoid arthritis (RA), and steroid-induced femoral head necrosis (SANFH). In this review, we introduce the signaling pathways and related factors of macrophage polarization, as well as their relationships with immune factors, OB, OC, and MSC. We also discuss the roles of macrophage polarization and bone immunity in various diseases of bone homeostasis imbalance, as well as the factors regulating them, which may help to develop new methods for treating bone metabolic disorders.

激素性股骨头坏死是由于糖皮质激素不正确使用导致股骨头内骨稳态失衡,股骨头周围血供受阻,造成股骨头缺血性坏死.细胞焦亡是近年来发现的一种由半胱天冬酶Caspase-1/4/5/11 介导新的促炎性细胞程序性死亡,主要表现为细胞膜破裂,释放大量的促炎因子,募集更多的炎性细胞,发生机体级联反应.细胞焦亡广泛参与各种疾病的发生,其中由细胞焦亡导致的炎症反应是导致激素性股骨头坏死发生、发展的重要环节.从细胞焦亡的定义以及细胞焦亡途径中的关键因子NLRP3 炎性小体、Caspase-1、核转录因子-κB、白细胞介素与激素性股骨头坏死的关系出发,探讨激素性股骨头坏死的发病机制,以期为防治提供新思路.

近年研究发现,激素性股骨头坏死的发生、发展受多机制共同调控,而线粒体自噬紊乱就是其中主要机制之一.线粒体自噬紊乱可导致骨髓间充质干细胞凋亡,成骨细胞骨形成减少,破骨细胞骨吸收增加,及骨内血管内皮修复受阻等,从而诱导激素性股骨头坏死发生.从分子及细胞层面阐述线粒体自噬的相关机制及其对骨髓间充质干细胞、成骨细胞、破骨细胞与骨内血管内皮细胞的影响,以期为靶向调控线粒体自噬防治激素性股骨头坏死提供新思路.

激素性股骨头坏死（steroid-induced necrosis of the femoral head，SNOFH）是临床上常见的一种骨科疾病，具有治愈难度大、临床预后差等特点。中国每年的SNOFH患者人数还在呈逐年上升的趋势，严重威胁人类的健康。长期不规范或短期大量使用激素（GC）是造成该病发生的重要原因，目前临床上对SNOFH多采取髋关节置换等手术治疗手段，其存在对患者伤害大、花费较高等局限性。近年来，随着对中医药研究的不断深入与创新，运用中医药方法治疗SNOFH在临床上被广泛应用。SNOFH发生的中医病机主要是肾虚血瘀，故临床多采取补肾活血类中药单体及复方对SNOFH进行治疗。且中医药具有治疗效果明显，毒副作用小，花费少等优点。在此之前的研究大都从中医辨证的方向阐述中医药对SNOFH的影响，本文将从分子生物及细胞生物学角度来阐述中医药对SNOFH的影响机制。分泌型糖蛋白/β-链蛋白（Wnt/β-catenin）信号通路作为与骨骼密切相关的经典信号通路，其通过促进骨髓间充质干细胞更新、增强成骨细胞的活性并抑制其发生凋亡，从而调节骨组织的代谢平衡，增加骨密度，在骨形成的过程中发挥重要作用。近年来运用中药单体及复方调控Wnt/β-catenin信号通路治疗SNOFH已成为当今研究的新热点。现就中医药通过调控Wnt/β-catenin信号通路防治SNOFH的研究进展做一综述，以期为中医药治疗SNOFH的应用提供参考。