Recent advances in phosphatases as new biomarker in personalized medicine.

Respiratory inflammatory diseases disrupt bone metabolism and cause pathological bone loss. The lung-bone axis is established in chronic diseases like asthma and cystic fibrosis but is less studied in acute lung injury (ALI), recently implicated in COVID-19-induced bone loss. This study examined the effects of LPS-induced ALI on bone phenotype and explored the role of 2-N, 6-O sulfated chitosan (26SCS) in mitigating pneumonia-induced bone loss via inflammatory response modulation. Our findings show that 26SCS effectively reaches bone tissue after oral administration. It promotes macrophage polarization to the M2 phenotype, alleviating immune cascade reactions and inhibiting osteoclast-mediated bone resorption. Increased M2 macrophages support type H vessel formation, enhancing inflammatory bone vascularization. These effects foster a favorable osteogenic microenvironment and mitigate ALI-induced bone loss. While dexamethasone is effective in reducing inflammation, it can aggravate ALI-induced bone loss. Our research offers a therapeutic strategy targeting the lung-bone axis for inflammation-induced bone loss.

This study investigated an upper-extremity exoskeleton for machine learning–based discrimination of orthopedic shoulder pathology and identification of discriminative temporal features. Twelve patients with shoulder impairments and thirty healthy controls performed eight standardized tasks. Logistic regression with stratified 5-fold cross-validation was used for classification. Temporal effect sizes were computed using pointwise Cohen’s d, and permutation-based phase ablation quantified the contribution of movement phases to AUROC. Classification performance ranged from 0.70 to 1.00, with six tasks achieving AUROC ≥ 0.90. Mid-cycle phases dominated in flexion and abduction tasks, whereas early and late phases were most informative for rotational movements, supporting interpretable, phase-aware ML models.

Bone remodeling depends on the balance between osteoblast-mediated formation and osteoclast-mediated resorption, with disruption contributing to osteoporosis and other osteolytic diseases. Nitric oxide (NO) serves as a critical regulator of skeletal homeostasis and inflammatory signaling.Panax notoginseng, traditionally used in bone trauma, contains notoginsenoside R1 (NGR1) as a principal bioactive component. However, the mechanisms by which NGR1 modulates osteoclastogenesis remain unclear. A network pharmacology approach was employed to predict NGR1 targets and their intersection with NO regulation and osteoclastogenesis. Protein-protein interaction (PPI) analysis, GO/KEGG enrichment, and molecular docking were conducted to identify hub genes and pathways. Experimental validation was performed using CD14⁺ monocytes differentiated into osteoclasts under RANKL and M-CSF stimulation. TRAP staining, cathepsin K expression, and NO production assays were used to assess osteoclast formation, functionality, and signaling modulation. Network analysis identified 79 overlapping targets between NGR1, NO regulation, and osteoporosis, highlighting hub genes involved in inflammatory signaling (IL-1β, IL-6, TNF, PTGS2), apoptosis (AKT1, CASP3, BCL2, ESR1), and signal transduction (STAT3, MAPK3). Docking studies indicated strong binding potential of NGR1 to AKT1, PTGS2, MAPK3, and CASP3. Experimentally, NGR1 inhibited osteoclastogenesis in a dose-dependent manner, with significant suppression at ≥ 50μM. NGR1 and the NO scavenger PTIO showed comparable inhibitory effects, in contrast to the pro-osteoclastogenic effects of the NO donor SNP. NGR1 treatment also reduced NO production and impaired osteoclast function, as demonstrated by decreased TRAP and cathepsin K expression. This study provides the first comprehensive evidence that NGR1 acts as a multi-target regulator of osteoclastogenesis through NO-dependent mechanisms. By integrating the suppression of NO levels with predicted modulation of inflammatory, apoptotic, and signal transduction pathways, NGR1 suppresses osteoclast differentiation and function. These findings advance the molecular understanding ofPanax notoginsengin bone health and support NGR1 as a promising therapeutic candidate for pathological bone loss, warranting further in vivo and translational investigation.

Scapular winging occurs as an abnormal protrusion of the scapula due to nerve injury, muscle weakness, bone, or joint pathology. The main muscular stabilizers of the scapula include the serratus anterior, trapezius, rhomboid major and minor, levator scapulae, and pectoralis minor. Needle electromyography (EMG) has historically been used as one of the primary diagnostic tests for evaluating this finding. However, sampling of these muscles can be technically difficult and carries risks for complications. Muscle ultrasound (MUS) can also reliably identify abnormalities in the muscles involved in scapular stabilization while offering the benefit of rapid side-to-side comparison and improved patient comfort. This study aims to highlight the concordance of ultrasound and EMG findings using our published MUS protocol in patients with scapular winging. A retrospective analysis was performed of 13 patients who presented to an electrodiagnostic (EDX) laboratory with the referral diagnosis of "scapular winging" or "scapular dyskinesis." All patients underwent MUS testing of scapular muscles according to a previously published protocol followed by EMG of muscles deemed relevant by the clinician. Seven patients were found to have a neurogenic cause of their scapular winging and in those patients, all had both EMG and MUS abnormalities. MUS was found to have a sensitivity of 87.5%, specificity of 95.7%, and individual muscle concordance with EMG of 90.6%. There is high concordance between EMG and MUS in patients with scapular winging. This combined with potential advantages of the MUS modality supports their concurrent use in patients with scapular winging.

Background: Treatment of chronic painful insertional Achilles tendinopathy is known to be challenging. If non-surgical treatment does not give sufficient relief of symptoms, surgery may be indicated. Treatment with ultrasound (US)- and colour Doppler (CD)-guided wide-awake-local-anaesthetic-no-tourniquet (WALANT) surgery for insertional Achilles tendinopathy is a new approach with promising clinical results. This study aimed to evaluate clinical results of this new approach on patients suffering from insertional Achilles tendinopathy. Methods: Forty-eight consecutive patients with 53 symptomatic tendons (33 men with 34 tendons, mean age 49.3 ± 12.0 years; 14 women with 18 tendons, mean age 55.0 ± 7.4 years) and a duration of more than 12 months with painful insertional Achilles tendinopathy (including tendon, bursae, bone, and plantaris pathology) were included. US- and CD-guided WALANT surgery with removal of pathological bursae, bone, and tendons was used. Immediate weight-bearing loading was allowed, followed by a structured rehabilitation protocol for the first 12 weeks after surgery. VISA-A scores before and after surgery and a questionnaire that evaluated subjective satisfaction with the treatment and current activity level were used. Results: In total, 42/48 patients with 46/53 tendons participated in a 3-year follow-up (mean 34 ± 9 months) by an independent examiner; 39/42 patients with 43/46 tendons were satisfied (n = 37) with the treatment. The mean VISA-A score increased significantly from 41.9 ± 18.2 pre-operatively to 87.7 ± 18.2 post-operatively (p < 0.001). There were three surgical complications, two superficial wound infections, and one minor wound rupture. Conclusions: Patients who suffered from chronic painful insertional Achilles tendinopathy treated with US- and CD-guided WALANT surgery followed by immediate weight-bearing showed high patient subjective satisfaction rates and better functional scores at the 3-year follow-up with a low complication rate. This novel treatment approach warrants more study, including randomised trials comparing it against traditional surgical procedures according to Nunley and Keck and Kelly.

The transforming growth factor-β (TGF-β) and bone morphogenetic protein (BMP) signaling pathways are pivotal regulators of cellular processes, playing indispensable roles in embryogenesis, postnatal development, and tissue homeostasis. These pathways are particularly critical within the skeletal system, as they coordinate osteogenesis, chondrogenesis, and bone remodeling through intricate molecular mechanisms. TGF-β/BMP signaling is primarily transduced via canonical Smad-dependent pathways (e.g., ligands, receptors, and intracellular Smads) and the non-canonical Smad-independent (e.g., p38 mitogen-activated protein kinase, MAPK) cascade. Both pathways converge on master transcriptional regulators, including Runx2 and Osterix, and their precise coordination is indispensable for skeletal development, maintenance, and repair. The dysregulation of TGF-β/BMP signaling contributes to a spectrum of skeletal dysplasia and bone pathologies. Advances in molecular genetics, particularly gene-targeting strategies and transgenic mouse models, have deepened our understanding of the spatiotemporal control of TGF-β/BMP signaling in bone and cartilage development. Moreover, emerging research underscores extensive crosstalk between TGF-β/BMP and other critical pathways, such as Wnt/β-catenin, mitogen-activated protein kinase (MAPK), parathyroid hormone (PTH)/PTH-related protein (PTHrP), fibroblast growth factors (FGF), Hedgehog, Notch, insulin-like growth factors (IGF)/insulin-like growth factors receptor (IGFR), Mammalian target of rapamycin (mTOR), and autophagy, forming an integrated regulatory network that ensures skeletal integrity. Our review synthesizes the current knowledge on the molecular components, regulatory mechanisms, and functional integration of TGF-β/BMP signaling in skeletal biology, with an emphasis on its roles in development, regeneration, and disease. By elucidating the molecular underpinnings of TGF-β/BMP pathways and their contextual interactions, we aim to highlight translational opportunities and novel therapeutic strategies for treating skeletal disorders.

To evaluate the efficacy and outcomes of extracorporeal shockwave therapy (ESWT) for bone pathologies including fractures, osteonecrosis/avascular necrosis, bone stress injury (BSI), medial tibial stress syndrome (MTSS), and bone marrow edema syndrome (BMES). Systematic review. Search performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses of 3 databases: Cochrane Library, Embase (Elsevier), and PubMed (NLM). Studies included randomized controlled trials, cohort studies, case series, and case reports that investigated the efficacy of ESWT for the management of BSI, BMES, MTSS, delayed or nonunion fracture, or osteonecrosis/avascular necrosis of bone. Fifty-three studies with 1835 adult patients (608 women, 910 men, 317 unspecified) were included. Studies were defined using Oxford level of evidence rating: 7 level I (13.2%), 4 level II (7.5%), 4 level III (7.5%), 24 level IV (45.2%), and 14 level V (26.4%). Four of 7 level I studies showed similar effectiveness of ESWT compared with surgery for the treatment of long bone nonunion fractures (n = 1) and early stage osteonecrosis of the femoral head (n = 1), exercise program for MTSS (n = 1), and medication management for BMES (n = 1). Efficacy for management of BSI had lower level of evidence. Twenty-two studies reported on safety with no significant adverse events. The limited high-level studies suggest ESWT may offer an effective noninvasive treatment of most bone pathologies with favorable safety profile. Additional high-quality studies particularly in BSI may inform use of ESWT for bone pathologies.

Background/Objectives: Surgical management of atypical femoral fractures (AFFs) stabilized with intramedullary (IM) nailing is frequently challenged by delayed union or nonunion due to the severely suppressed bone turnover characteristic of bisphosphonate-related bone pathology, often leading to a hypertrophic nonunion-like state at the fracture site. This consecutive case series aimed to evaluate the effectiveness of intraoperative percutaneous decortication at the hypertrophic cortex in promoting rapid bone healing in complete AFFs. Methods: This was a single-center consecutive case series of patients with complete atypical femoral fractures (AFFs) treated with intramedullary nailing and adjunctive percutaneous decortication since February 2021. The standardized surgical protocol—including percutaneous decortication performed through a small anterolateral incision using an osteotome to create bone chips and stimulate the sclerotic cortex—was applied prospectively to all consecutive patients from February 2021. Of the 20 patients who underwent surgery during this period, 14 with sufficient radiographic follow-up were included in the final retrospective analysis. Data collected included patient demographics, duration of bisphosphonate use, fracture location (diaphyseal vs. subtrochanteric), operative details (including iatrogenic fracture), and radiographic bone union time. Bone union was assessed on serial radiographs by two independent observers. Results: All 14 patients were female, with a median age of 75 years (IQR 67–79 years). Thirteen patients (92.9%) had prior bisphosphonate exposure for a median of 4.5 years (IQR 3–10 years). Six fractures were subtrochanteric fractures, and six were complicated by iatrogenic fracture during nail insertion. Postoperative teriparatide was administered to six patients. Radiographic bone union was achieved in all 14 patients at a median of 19 weeks (IQR 16–22 weeks; range 16–24 weeks). No major complications (infection, implant failure, nonunion, or neurovascular injury) occurred during follow-up. Conclusions: Percutaneous decortication is a simple, safe, and biologically plausible adjunct to intramedullary nailing. In this series of 14 elderly women with long-term bisphosphonate exposure (median 4.5 years), the technique was associated with 100% radiographic union at a median of 19 weeks without major complications, suggesting a promising strategy that warrants validation in larger, controlled trials.

Fibrodysplasia ossificans progressiva (FOP) is a rare genetic disorder in which a mutation in ACVR1/ALK2 drives progressive heterotopic ossification. However, how this mutation enforces a persistent pro-osteogenic state is unclear. Here, we show that the Acvr1 R206H mutation remodels chromatin architecture and accessibility through hyperactive BMP-SMAD and Rho/ROCK signaling, activating transcription factor networks that drive osteochondrogenic gene expression. These chromatin changes are dynamic and reversible with targeted pathway inhibition, revealing therapeutic potential to restore mesenchymal cell plasticity and prevent pathological bone formation.

The bone marrow niche is a complex microenvironment composed of stromal, endothelial, immune and hematopoietic cells. Dysregulated interactions within this niche can contribute to hematological malignancies and also occur in the context of solid cancer metastases. Here, we present a standardized three-dimensional human bone marrow (3D-BOM) model that recapitulates key features of the human niche. Indeed, we show that monocytes/macrophages from different sources acquire enhanced pro-inflammatory phenotype in 3D compared to 2D cultures. Hematopoietic progenitor cells are also influenced by this 3D niche while maintaining stemness characteristics over extended serial culture. Single-cell transcriptomics analysis highlighted human-like stromal and endothelial cells heterogeneity. In addition, we observed monocyte/macrophage and endothelial cell remodeling in the context of acute myeloid leukemia, suggesting dynamic interactions within the 3D-BOM. These findings highlight the potential of this model to investigate cellular dynamics underlying human bone marrow physiology and pathology.

Central tarsal bone (CTB) fractures are challenging to diagnose, and cross-sectional imaging is required for definitive characterization and surgical planning. This retrospective case series aims to provide the first description of high-field (3-T) MRI characteristics of CTB fractures, concurrent pathology, and clinical presentation in 8 performance horses. 8 horses (9 limbs) diagnosed with a CTB fracture on high-field MRI at one tertiary referral hospital between 2013 and 2023 were identified via electronic medical records search. Quarter Horses (6 of 8) used for Western performance disciplines, a Lusitano (1 of 8) used for Dressage, and a Thoroughbred (1 of 8) used for polo, with ages ranging from 3 to 20 years (mean, 8.4 years), were included. Lameness onset was chronic in the majority of cases (5 of 8), with grades ranging from 3/5 to 4/5. Lameness was localized to the proximal metatarsus (4 of 6), distal tarsal joints (1 of 6), or tarsocrural joint (1 of 6). A suspected CTB fracture was identified on radiographs prior to MRI in only 1 limb. Fractures were complete (6 of 9) or incomplete (3 of 9) with a dorsomedial to plantarolateral orientation occurring from 36° to 62° medial to the sagittal plane (mean, 52°). There was severe sclerosis (9 of 9) and mild (4 of 9), moderate (4 of 9), or severe (1 of 9) bone edema-like signal associated with all fractures. High-field MRI enabled diagnosis and detailed evaluation of CTB fracture configuration and concurrent bone and soft tissue pathology. Dorsomedial-plantarolateral oblique radiographic projections at approximately 50° medial to the sagittal plane may improve initial CTB fracture identification in performance horses.

Imaging for Ossiculoplasty.

Purines and their receptors play a role in the regulation of stem cell survival, proliferation, and differentiation. They are responsible for the osteogenic differentiation of stem cells by activating many signaling pathways and enhancing the expression of different osteogenic factors, including bone morphogenetic proteins, runt-related transcription factor 3, alkaline phosphatase (ALP), etc. Here, a 2,6,9-trisubstituted adenine derivative is reported, with negligible cytotoxicity and potent osteogenic potential as demonstrated with mouse myoblast (C2C12 cells) and murine preosteoblasts (MC3T3E1 cells). Osteogenic activity of the derivative (Compound 1) is supported by increased expression of ALP and enhanced calcium deposition observed with alizarin staining within cells. Thus, the reported adenine derivatives can serve as potential therapeutics for bone fractures as an injectable therapeutic opening avenue for cell-free therapy.

Staphylococcus aureus manipulates osteocytes to cause persistent chronic osteomyelitis and antibiotic resistance via pyroptosis pathway suppression.

Dysregulated neutrophils contribute to bone loss in renal osteodystrophy by enhancing osteoclastogenesis: Insights from integrated bioinformatics and experimental validation.

Cajanin transcriptionally disrupts the Siglec15/NFATc1 signaling cascade to attenuate osteoclast fusion and bone resorption.

Gut microbiota-derived indole-3-Acetic Acid attenuates skeletal fluorosis via AHR-mediated suppression of Wnt/β-Catenin signaling.

Periodontitis is a predominant persistent inflammatory disease marked by consistent destruction of tooth-supporting tissues including periodontal ligament and alveolar bone. Although some cytokines have been identified as key mediators, the upstream regulatory molecules that drives this pathological bone loss remains elusive. This study explores the mechanistic role of lncRNA ZFAS1 in the dysregulated bone remodeling of periodontitis microenvironment. We utilized single-cell and bulk RNA sequencing to profile cellular and molecular landscape in healthy and diseased periodontal tissues. GSEA analysis of bulk transcriptomes confirmed a significant activation of osteoclast-related pathways in disease (NES = 1.7, FDR q = 0.025). Findings were validated through qPCR, histology, and immunohistochemistry. The gain- and loss-of-function models in RAW264.7 and MC3T3-E1 cells to characterize the role of lncRNA ZFAS1 in vitro. The scRNA-seq analysis unveiled a marked 11-fold increase in osteoclast-osteoblast ratio in periodontitis, which was further confirmed histologically. This shift was accompanied by a specific inflammatory profile, and a marked upregulation of lncRNA ZFAS1 in diseased tissues. Notably, ZFAS1 expression showed a robust positive correlation with early osteoclast marker genes NFATC1 (R2 = 0.2056, p = 0.015) and TRAP1 (R2 = 0.784, p < 0.0001) but not the late-stage effector CTSK (R2 = 0.0011, p = 0.792). We confirmed that lncRNA ZFAS1 expression was precisely induced by the synergetic effect of differentiation (RANKL) and inflammatory (LPS) signals. Functionally, lncRNA ZFAS1 overexpression in RAW264.7 potentiated osteoclastogenesis, enhanced TRAP-positive osteoclasts and increased resorptive gene expression (NFATC1, Dcstamp, ACP5, CTSK, V-ATPase d2), while its knockdown exhibited the opposite effect. In contrast, lncRNA ZFAS1 knockdown in MC3T3-E1 boosted differentiation and matrix mineralization, augmented osteoblast-related gene expression (Runx2, ALP, OCN). In summary, lncRNA ZFAS1 is a critical driver of inflammatory bone loss, functioning as a dual-path regulator that promotes osteoclastogenesis and inhibits osteoblastogenesis. Its physiological role as a negative osteogenic regulator is evidenced by its downregulation during normal differentiation, highlighting its therapeutic potential for periodontitis and related conditions.

Adaptive smart hydrogels driving precision bone healing in pathological contexts.