Background: Alcohol abuse is known to be a leading risk factor for atraumatic osteonecrosis of the femoral head (ONFH), in which the suppression of osteogenesis plays a critical role. Cordycepin benefits bone metabolism; however, there has been no study to determine its effect on osteonecrosis. Methods: Human bone mesenchymal stem cells (hBMSCs) were identified by multi-lineage differentiation. Alkaline phosphatase (ALP) activity, RT-PCR, western blots, immunofluorescent assay and Alizarin red staining of BMSCs were evaluated. A rat model of alcohol-induced ONFH was established to investigate the protective role of cordycepin against ethanol. Hematoxylin & eosin (H&E) staining and micro-computerized tomography (micro-CT) were performed to observe ONFH. Apoptosis was assessed by TdT-mediated dUTP nick end labeling (TUNEL). Immunohistochemical staining was carried out to detect OCN and COL1. Results: Ethanol significantly suppressed ALP activity, decreased gene expression of OCN and BMP2, lowered levels of RUNX2 protein, and reduced immunofluorescence staining of OCN and COL1 and calcium formation of hBMSCs. However, these inhibitory effects were attenuated by cordycepin co-treatment at concentrations of 1 and 10 µg/mL Moreover, it was revealed that the osteo-protective effect of cordycepin was associated with modulation of the Wnt/β-catenin pathway. In vivo, by micro-CT, TUNEL and immunohistochemical staining of OCN and COL1, we found that cordycepin administration prevented alcohol-induced ONFH. Conclusion: Cordycepin treatment to enhance osteogenesis may be considered a potential therapeutic approach to prevent the development of alcohol-induced ONFH.

Aims: Alcoholism is a well-known detrimental factor in fracture healing. However, the underlying mechanism of alcohol-inhibited fracture healing remains poorly understood. Methods: MicroRNA (miR) sequencing was performed on bone mesenchymal stem cells (BMSCs). The effects of alcohol and miR-19a-3p on vascularization and osteogenic differentiation were analyzed in vitro using BMSCs and human umbilical vein endothelial cells (HUVECs). An in vivo alcohol-fed mouse model of femur fracture healing was also established, and radiological and histomorphometric analyses were used to evaluate the role of miR-19a-3p. The binding of miR-19a-3p to forkhead box F2 (FOXF2) was analyzed using a luciferase reporter assay. Results: miR-19a-3p was identified as one of the key regulators in the osteogenic differentiation of BMSCs, and was found to be downregulated in the alcohol-fed mouse model of fracture healing. In vitro, miR-19a-3p expression was downregulated after ethanol administration in both BMSCs and HUVECs. Vascularization and osteogenic differentiation were independently suppressed by ethanol and reversed by miR-19a-3p. In addition, the luciferase reporter assay showed that FOXF2 is the direct binding target of miR-19a-3p. In vivo, miR-19a-3p agomir stimulated callus transformation and improved the alcohol-impaired fracture healing. Conclusion: This study is the first to demonstrate that the miR-19a-3p/FOXF2 axis has a pivotal role in alcohol-impaired fracture healing, and may be a potential therapeutic target. Cite this article: Bone Joint Res 2022;11(6):386–397.

Natural fracture healing is most efficient when the fine-tuned mechanical force and proper micromotion are applied. To mimick this micromotion at the fracture gap, a near-infrared-II (NIR–II)–activated hydrogel was fabricated by integrating two-dimensional (2D) monolayer Nb₂C nanosheets into a thermally responsive poly(N-isopropylacrylamide) (NIPAM) hydrogel system. NIR–II–triggered deformation of the NIPAM/Nb₂C hydrogel was designed to generate precise micromotion for co-culturing cells. It was validated that micromotion at 1/300 Hz, triggering a 2.37-fold change in the cell length/diameter ratio, is the most favorable condition for the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). Moreover, mRNA sequencing and verification revealed that micromotion-induced augmentation was mediated by Piezo1 activation. Suppression of Piezo1 interrupts the mechano-sensitivity and abrogates osteogenic differentiation. Calvarial and femoral shaft defect models were established to explore the biocompatibility and osteoinductivity of the Micromotion Biomaterial. A series of research methods, including radiography, micro-CT scanning, and immunohistochemical staining have been performed to evaluate biosafety and osteogenic efficacy. The in vivo results revealed that tunable micromotion strengthens the natural fracture healing process through the sequential activation of endochondral ossification, promotion of neovascularization, initiation of mineral deposition, and combinatory acceleration of full-thickness osseous regeneration. This study demonstrated that Micromotion Biomaterials with controllable mechanophysical characteristics could promote the osteogenic differentiation of BMSCs and facilitate full osseous regeneration. The design of NIPAM/Nb₂C hydrogel with highly efficient photothermal conversion, specific features of precisely controlled micromotion, and bionic-mimicking bone-repair capabilities could spark a new era in the field of regenerative medicine.

Aims: Osteoporosis (OP), an age-related skeletal disorder, is characterized by excessive bone resorption driven by osteoclast overactivation, reactive oxygen species (ROS) accumulation, and chronic inflammation. Although the mitochondria-targeted antioxidant ergothioneine (EGT) has shown potential in regulating bone metabolism, its specific preventive mechanism in oestrogen-deficient osteoporosis remains unclear. Therefore, this study aimed to elucidate the preventive effects of EGT and its underlying mechanisms when administered early after ovariectomy. Methods: Using an oestrogen-deficient mouse model, EGT was administered immediately after modelling to evaluate its preventive effects against bone loss and microstructural deterioration. In vivo analyses included assessments of bone resorption parameters, B-cell precursor populations, and the bone marrow inflammatory status. Complementary in vitro experiments were conducted to examine the influence of EGT on mitochondrial ROS levels, p65 phosphorylation, NF-κB/NFATc1 signalling pathway activity, and osteoclast differentiation. Results: Preventive administration of EGT significantly mitigated ovariectomy-induced bone loss and preserved bone microstructure. This was achieved through the suppression of osteoclast activity, modulation of B-cell precursors, and reversal of the pro-inflammatory bone marrow microenvironment. Mechanistically, EGT reduced mitochondrial ROS generation, inhibited p65 phosphorylation and nuclear translocation, and consequently disrupted the nuclear factor κB (NF-κB)/NFATc1 signalling axis, ultimately inhibiting osteoclastogenesis. Conclusion: The findings of this study indicate that ergothioneine has the potential to prevent osteoporosis. It bidirectionally regulates bone homeostasis by targeting the ROS–NF-κB axis, systemically remodelling a protective anti-inflammatory bone marrow microenvironment while directly inhibiting osteoclast activation and differentiation. These results underscore the translational value of EGT as an early preventive strategy for oestrogen-deficient osteoporosis. Cite this article: Bone Joint Res 2026;15(3):248–263.

Background. Hip fracture is one of the major risk factors of global mortality and disability. The aim of this study was to map the pattern of intertrochanteric femoral fractures in China, providing a pilot national dataset and basis for medical policy proposals. Methods. A multistage probability sampling strategy was applied in the national baseline survey. Thirty provinces in mainland China were included in this survey. A standardized questionnaire survey was conducted to collect information about basic characteristics such as age, working seniority, hospital level, and residence, with two other parts including perioperative and postoperative treatment parameters. Odds ratios and 95% confidence interval were used to determine essential statistical differences. The proportion of the options in each region was compared using the chi-square (χ²) test. The histogram and choropleth map of the monthly number of admissions were created using Excel 2016 to show the distribution characteristics. Results. In total, 1065 valid responses were included, representing a 96.7% survey capture rate. Perioperative treatment and postoperative care distinctly varied across regions and hospital levels. The monthly number of admissions was relatively lower in the Northern region, with higher proportion of hospitalizations to secondary hospitals compared with the Eastern region. The patients in the Eastern region or tertiary hospitals had shorter preoperative waiting time and hospitalization period. Conclusions. We found apparent geographic variations in intertrochanteric femoral fractures in this study, and the data can be used for drafting national healthcare plans and medical policies.