Background. Diabetic neuropathic osteoarthropathy (DNOAP) is a rare and easily missed complication for diabetes that leads to increased morbidity and mortality. DNOAP is characterized by progressive destruction of bone and joint, but its pathogenesis remains elusive. We herein aimed to investigate the pathological features and pathogenesis of the cartilages damage in DNOAP patients. Methods. The articular cartilages of eight patients with DNOAP and eight normal controls were included. Masson staining and safranine O/fixed green staining (S‐O) were used to observe the histopathological characteristics of cartilage. The ultrastructure and morphology of chondrocytes were detected by electron microscopy and toluidine blue staining. Chondrocytes were isolated from DNOAP group and control group. The expression of receptor activator of nuclear factor kappaB ligand (RANKL), osteoprotegerin (OPG), interleukin‐1 beta (IL‐1β), interleukin‐6 (IL‐6), tumor necrosis factor‐alpha (TNF‐α), and Aggrecan protein was evaluated by western blot. Reactive oxygen species (ROS) levels were measured using a 2′,7′‐dichlorofluorescin diacetate (DCFH‐DA) probe. The percentage of apoptotic cells was determined by flow cytometry (FCM). The chondrocytes were cultured with different glucose concentrations to observe the expression of RANKL and OPG. Results. Compared with the control group, the DNOAP group showed fewer chondrocytes, subchondral bone hyperplasia, and structural disorder, and a large number of osteoclasts formed in the subchondral bone area. Moreover, mitochondrial and endoplasmic reticulum swellings were observed in the DNOAP chondrocytes. The chromatin was partially broken and concentrated at the edge of nuclear membrane. The ROS fluorescence intensity of chondrocyte in DNOAP group was higher than that in normal control group (28.1 ± 2.3 vs. 11.9 ± 0.7; P < 0.05). The expression of RANKL, TNF‐α, IL‐1β, and IL‐6 protein in DNOAP group was higher than that in normal control group, whereas OPG and Aggrecan protein were lower than that in normal control group (both P < 0.05). FCM showed that the apoptotic rate of chondrocyte in DNOAP group was higher than that in normal control group (P < 0.05). The RANKL/OPG ratio showed significant upward trend when the concentration of glucose was over than 15 mM. Conclusions. DNOAP patients tend to have severe destruction of articular cartilage and collapse of organelle structure including mitochondrion and endoplasm reticulum. Indicators of bone metabolism (RANKL and OPG) and inflammatory cytokines (IL‐1β, IL‐6, and TNF‐α) play an important role in promoting the pathogenesis of DNOAP. The glucose concentration higher than 15 mM made the RANKL/OPG ratio change rapidly.

Objectives: Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are an established first-line treatment for non-small cell lung cancer (NSCLC) patients with sensitizing mutations because of their remarkable efficacy and favorable tolerability profiles. However, rare and severe adverse reactions during their application require attention. Cases of diabetic ketoacidosis (DKA) associated with EGFR-TKI therapy have seldom been reported and the underlying mechanism remains unclear. Case presentation: We present the case of a 64-year-old female patient with immune checkpoint inhibitor-induced diabetes mellitus (ICI-DM) on aumolertinib (a third-generation EGFR-TKI, 110 mg daily) for the treatment of NSCLC admitted to the hospital with frequent episodes of DKA. Owing to a recurrent DKA episode following a reduced dosage (55 mg daily), aumolertinib was suspended permanently. After full recovery from the DKA, the patient was switched to osimertinib (80 mg daily). Insulin resistance in the patient was assessed using a hyperinsulinemic-euglycemic clamp. She was maintained on standard-dose osimertinib and insulin therapy after discharge and remained asymptomatic during the outpatient follow-up. Conclusion: Owing to the protocol-defined strict inclusion and exclusion criteria, some potentially serious adverse reactions may not be as commonly observed in clinical trial settings. Aumolertinib-induced exacerbation of insulin resistance can precipitate a spectrum of hyperglycemia, ranging from mild elevations to severe DKA, which highlights the necessity of blood glucose monitoring throughout the treatment course. By assessing a patient’s tolerance profile for EGFR-TKIs-aggravated insulin resistance using the insulin clamp technique, clinicians can optimize antineoplastic regimens, such as switching from aumolertinib to osimertinib in this case.

Aims: This study aims to investigate the molecular differences of cellular heterogeneity, metabolic, and cell death signatures between osteoarthritis (OA) and Kashin-Beck disease (KBD) at single-cell resolution. Methods: Single-cell RNA sequencing was performed on 139,943 chondrocytes isolated from 17 human cartilage samples, comparising three healthy controls, eight patients with OA, and six patients with KBD. Chondrocyte populations were identified using the Louvain algorithm and systematically compared across the three groups. Differentially expressed genes, functional enrichment, metabolic activity, and cell death-related signatures were analyzed. Key findings were further validated using immunohistochemistry staining and quantitative real-time polymerase chain reaction (PCR). Results: We found that pre-hypertrophic chondrocytes (preHTC), fibrocartilage chondrocytes (FC), pre-inflammatory chondrocytes (preInfC), and inflammatory chondrocytes (InfC) populations were enriched in OA, whereas proliferation chondrocytes (ProC) and homeostasis chondrocytes (HomC) predominated in KBD. In OA cartilage, OA-associated genes displayed upregulation of extracellular matrix (ECM) remodelling and immune activation pathways in preInfC and InfC populations. In contrast, KBD-associated genes exhibited marked activation of endoplasmic reticulum stress and oxidative stress responses in ProC-2, ProC-3, and HomC-2 subpopulations. OA was characterized by metabolic reprogramming with enhanced ECM remodelling and inflammation-related pathways, whereas KBD exhibited a globally suppressed metabolic profile. Additionally, ferroptosis activity was significantly higher in KBD cartilage compared with OA and control cartilage, with the strongest enrichment observed in ProC and HomC populations. Conclusion: Although OA and KBD chondrocytes were broadly conserved across 11 identified populations, they exhibited distinct disease-specific transcriptional profiles, metabolic activities, and cell death signatures. These findings enhance our understanding of chondrocyte heterogeneity and identify the InfC population in OA, as well as the ProC and HomC populations in KBD, as potential targets for therapeutic intervention. Cite this article: Bone Joint Res 2026;15(11):1327–1340.

Charcot neuroarthropathy (CN) is a debilitating joint disorder that predominantly affects patients with neuropathy, particularly those with diabetic periph