Search Results (231)

Hajdu–Cheney syndrome (HCS) is a rare genetic skeletal disorder caused by truncating variants of NOTCH2, characterized by progressive bone resorption and marked phenotypic heterogeneity. Despite advances in understanding Notch signaling in skeletal biology, longitudinal clinical data tracking disease evolution from early childhood through adolescence are lacking. Here, we report a rare longitudinal intrafamilial observation of HCS in a mother and her son carrying the same NOTCH2 pathogenic variant, providing novel insights into disease evolution and therapeutic response. Over extended follow-up, the son exhibited early vertebral fragility despite preserved or supranormal bone mineral density (BMD), whereas the mother developed severe osteoporosis, progressive acro-osteolysis, and multiple vertebral fractures. Longitudinal analysis revealed a dissociation between vertebral fragility and densitometric decline, challenging the paradigm that low BMD is the primary driver of skeletal morbidity in HCS. Treatment responses differed between the two patients, with bisphosphonate therapy in the son associated with stabilized BMD without altering vertebral structural progression, and denosumab in the mother associated with increased BMD, but not preventing progression of acro-osteolysis. Additionally, the emergence of extra-skeletal features during adolescence expands the phenotypic spectrum of HCS and suggests previously unrecognized systemic involvement. These data highlight intrinsic limitations of current therapeutic strategies and emphasize the need for targeted interventions addressing sustained Notch2 activation. Our findings contribute to the understanding of the natural history and therapeutic challenges of HCS, providing the framework for future mechanistic and translational research. Full article

Osteocytes, once viewed mainly as passive bone-embedded cells, are now recognized as active regulators of the metastatic bone niche. Emerging evidence indicates that these cells integrate mechanical, inflammatory, and tumor-derived cues to influence metastatic seeding, dormancy, reactivation, and lesion progression in bone. This review synthesizes current understanding of osteocyte contributions to skeletal metastasis. We discuss core signaling axes, including osteocyte-derived RANKL/OPG balance, Wnt antagonists (sclerostin/DKK1), mechanotransduction pathways (Piezo1 signaling and connexin-43 hemichannels), and osteocyte paracrine mediators (extracellular vesicles and senescence-associated factors), and examine how each axis modulates tumor cell dormancy, osteolysis, or osteoblastic progression. We then review translational strategies targeting osteocytes, recent preclinical and clinical insights. Emerging biomarkers (e.g., serum sclerostin, DKK1, bone turnover markers) and immune–skeletal imaging approaches are also considered. Controversies, including the paradoxical effects of sclerostin blockade and the identity of in vivo RANKL sources, are discussed. Finally, we outline key knowledge gaps and propose endpoints for future trials. In summary, an osteocyte-centric perspective reveals novel targets and strategies for managing bone metastases, guiding future translational research. Full article

Background: Cemented fixation remains the standard for total knee arthroplasty (TKA), with Palacos^® R considered the gold standard bone cement. However, more cost-efficient alternatives, like Biomet Bone Cement^® (BBC), require evaluation to confirm comparable outcomes. This retrospective 5-year study compares the clinical safety, performance, and radiographic outcomes of BBC versus Palacos-R in primary TKA, highlighting BBC’s potential as a comparable, cost-effective option amid the increasing cost of outpatient surgeries. Methods: This is a single-center, retrospective study of 128 consecutive patients undergoing primary TKA, evaluated over 5 years. The first 64 patients received Palacos-R, and the subsequent 64 patients received BBC. Radiographic outcomes, including cement gaps, radiolucency, periprosthetic osteolysis, and subsidence, were assessed using the Knee Society Radiographic scheme at immediate post-operative, 6-month, 1-year, 3-year, and 5-year intervals. Clinical outcomes were measured using the Knee Society Score (KSS) and the University of California Los Angeles Activity (UCLA) score. Statistical analyses included chi-square, Fisher’s exact tests, and t-tests (p < 0.05). Results: Cement gaps were significantly higher in the Palacos-R cohort at immediate postop (p = 0.0002) and 1-year (p = 0.0003), with no significant difference at 3 and 5 years. Radiolucency was non-progressive (<2 mm) in both cohorts. KSS was significantly higher in the Palacos-R group at 6 months, 1 year, and 3 years (p < 0.001), but equivalent at 5 years (p = 0.42). UCLA scores showed no differences. No revisions were required in either cohort. Conclusions: While BBC demonstrated comparable radiographic stability and clinical outcomes to Palacos at 5 years with no revisions in either cohort, the absence of preoperative KSS and UCLA scores is a major limitation that prevents adjustment for baseline function and limits interpretation of the early postoperative KSS differences. Full article

Background: Surgical management of adult patients with post-dysplastic coxarthrosis using total hip arthroplasty is technically demanding and carries an increased risk of complications. In cases of high iliac dislocation classified as Crowe type IV, restoring the acetabular component to the anatomical hip centre often requires femoral shortening osteotomy to enable safe reduction in the prosthetic joint. Nevertheless, long-term evidence on functional outcomes and prosthesis survival with this approach is limited. Methods: A retrospective cohort study included 19 patients with 22 cases of Crowe type IV post-dysplastic hip osteoarthritis treated with uncemented total hip arthroplasty (Pinnacle/S-ROM, DePuy, Warsaw, IN, USA) combined with transverse subtrochanteric femoral shortening osteotomy. Patients underwent serial clinical follow-up, including assessment of range of motion, measurement of limb-length discrepancy, and functional evaluation using the Harris Hip Score and the WOMAC questionnaire. Radiological assessment included evaluation of osteotomy union, implant positioning, and osteolysis on standardized radiographs. Vertical distances of the centre of rotation (CR), the tip of the greater trochanter (GT), and the tip of the lesser trochanter (LT) from both reference lines were measured bilaterally, and inter-side differences were calculated. The reference lines consisted of the line connecting the inferior margins of the ischial bones and the teardrop (TD) line. Results: All osteotomies united at a mean of 5.57 months, with a mean follow-up of 129 months. Mean limb-length discrepancy decreased from 5.27 cm to 1.5 cm, and mean hip flexion improved from 82.9° to 106°. Functional outcomes improved significantly, with mean WOMAC increasing from 55.4 to 80.1 (p < 0.001) and mean Harris Hip Score from 49.8 to 84.66 at up to 3 years of follow-up (p < 0.001). Osteotomy length correlated strongly with lesser trochanter–teardrop distance (p = 0.00000048). Complications included distal femoral fissure (27.3%) and revision (18%), with no infection or permanent neurological deficit. Conclusions: Total hip arthroplasty combined with subtrochanteric femoral shortening osteotomy for Crowe type IV post-dysplastic hip osteoarthritis appears to be a feasible and effective procedure in an experienced centre, providing reliable osteotomy healing and significant early functional improvement that is sustained over time. Limb-length discrepancy was reduced and satisfactory biomechanical restoration was achieved, with an acceptable complication profile and implant survival of 81.3% at long-term follow-up. The LT–TD parameter was identified as a potential predictor of osteotomy length, enabling the proposal of a preoperative planning equation. However, given the limited sample size and lack of validation, these findings should be interpreted cautiously. Further studies are needed to confirm their broader applicability. Full article

Background and Clinical Significance: Immunoglobulin G4-related disease (IgG4-RD) is a systemic immune-mediated fibroinflammatory disorder that can mimic infection or malignancy. Spinal involvement is exceedingly rare and usually limited to pachymeningitis or epidural pseudotumors. True vertebral bone destruction has been reported only sporadically. Case Presentation: A 54-year-old man presented to our emergency department with severe neck pain after a fall. CT and MRI revealed extensive osteolysis of the C1 posterior arch and odontoid process with atlantoaxial subluxation. Following a second inpatient fall, he developed acute tetraparesis. Emergency posterior occipitocervical fusion (C0–C4) with C1–C2 laminectomy and foramen magnum decompression was performed. Histopathology demonstrated dense lymphoplasmacytic infiltration and fibrosis with up to 36 IgG4⁺ plasma cells per high-power field and an IgG4⁺/IgG ratio > 40%, confirming IgG4-RD. The patient recovered substantial motor function postoperatively and regained independent ambulation after neurological rehabilitation. Conclusions: IgG4-RD can rarely present as destructive craniovertebral osteolysis with neurological compromise. Unexplained C1–C2 osteolytic lesions should prompt evaluation for IgG4-RD, a rare but treatable cause of cervical instability. Full article

Background/Objectives: Tenosynovial giant cell tumours (TGCT) are a group of mesenchymal tumours involving the synovium, bursae, and tendon sheaths, comprising two subtypes: nodular and diffuse. Although predominantly benign, diffuse forms can be locally aggressive, resulting in bone destruction. The pathogenesis of TGCTs is still poorly understood. The aim of this study was to systematically review the current literature on the factors, mechanisms, and markers involved in TGCT disease, focussing on their potential role in bone destruction. Methods: This systematic review was conducted using the PRISMA guidelines. A search was performed using PubMed, Scopus, and Cochrane Library, and all original scientific research into mechanisms/pathways/signalling involving TGCTs was included. Results: After the review process, 51 studies were included for data extraction. Extracted data included authorship, publication year, patient numbers and aetiology (nTGCT/dTGCT), demographics, investigative methods, and studied biological factors, mechanisms, and markers. Cross-tabulation of reported elements revealed 159 unique factors, with most appearing only once. Eight elements were reported five or more times: CSF1, CD68, Ki-67, MMP9, CD163, TRAP, TNF-α, and IL-1β. Although representing just 5% of all identified factors, these appeared in 69% of the included studies, highlighting their prominence in the literature. Conclusions: Apart from the well-known osteoclastogenesis factor CSF1, inflammatory cytokines (TNF-α and IL-1β) and monocyte–macrophage lineage makers (CD68, CD163) are signalling pathways key to TGCT disease progression and associated bone destruction. Full article

Background/Objectives: Streptococcus intermedius, a member of the Streptococcus anginosus group, is characterized by a marked propensity for abscess formation but only rarely causes native-joint septic arthritis. Involvement of the acromioclavicular (AC) joint is particularly uncommon. We describe a case of native AC joint septic arthritis due to S. intermedius in a patient with multiple predisposing factors and highlight diagnostic and management considerations. Methods: We report the clinical course of a 72-year-old man with poorly controlled type 2 diabetes mellitus who presented with progressive right shoulder pain, erythema, and swelling following recurrent minor skin abrasions from a newly adopted dog. Initial management for presumed inflammatory shoulder pathology included brief systemic corticosteroids and an ultrasound-guided intra-articular ketorolac injection. Magnetic resonance imaging (MRI) was performed after symptom progression. The patient underwent operative irrigation and debridement with collection of synovial fluid and deep tissue cultures. Blood cultures and transthoracic echocardiography were obtained to evaluate for systemic involvement. Results: MRI demonstrated multiloculated periarticular abscesses and osteolysis centered on the AC joint. Operative cultures yielded high colony counts of S. intermedius from synovial fluid and deep tissues. Blood cultures and echocardiography were negative. The patient required multiple operative debridements with irrigation, adjunctive local antibiotic therapy, and prolonged targeted β-lactam treatment. Clinical and radiographic improvement was achieved following surgical source control and antimicrobial therapy. Conclusions: Native AC joint septic arthritis due to S. intermedius is rare. Older age, uncontrolled diabetes, recent intra-articular intervention, and possible zoonotic inoculation from canine wound licking may represent contributory risk factors. Early imaging, prompt surgical source control, and guideline-concordant antimicrobial therapy are essential when bone and soft tissue involvement is present. Full article

Introduction: Ceramic-on-ceramic (CoC) articulation in total hip arthroplasty (THA) offers excellent wear characteristics but carries risks such as liner malseating and ceramic fracture. To solve these problems, monoblock acetabular cups with preassembled ceramic liners were developed to minimize technical errors and allow the use of larger femoral heads. This study aimed to evaluate the mid-term clinical and radiological outcomes of a ceramic monoblock acetabular cup system. Methods: A retrospective analysis was performed on 106 primary THAs in South Korean patients using the Maxera monoblock cup (Zimmer Biomet) between 2015 and 2018, with a minimum follow-up of 5 years. Clinical outcomes were assessed using the Harris Hip Score (HHS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and Visual Analog Scale (VAS). Radiologic evaluation included osteolysis and radiolucent lines. Normality of clinical variables was confirmed, and pre-to-postoperative comparisons were performed using paired t-tests. Results: The mean follow-up was 6.8 ± 1.4 years. The most common preoperative diagnosis was avascular necrosis (66.0%). Cups sized ≤52 mm were used in 80.2% of hips, allowing the frequent use of large femoral heads (32–40 mm). Clinical scores improved significantly: HHS from 37.0 ± 13.4 to 90.8 ± 6.2, WOMAC from 66.6 ± 11.5 to 7.6 ± 6.7, and VAS from 6.45 ± 1.1 to 1.1 ± 0.8 (p < 0.001). No osteolysis was observed. Radiolucent lines was appeared in four hips (3.7%) without evidence of migration or loosening. One cup fixation failure (0.9%) required revision. No cases of ceramic fracture, squeaking, or dislocation occurred. Conclusions: The ceramic monoblock acetabular cup demonstrated excellent mid-term clinical and radiological outcomes with a very low complication rate. The ability to reliably use large femoral heads likely contributed to enhanced joint stability. However, the absence of screw fixation and inability to directly visualize cup insertion require careful attention during cup impaction. Long-term studies with comparative cohorts are warranted. Full article

Giant cell tumor of bone (GCTB) is a distinctive, intermediate-grade primary bone neoplasm defined by a neoplastic mesenchymal stromal compartment and a prominent osteoclast-rich microenvironment. Although histologically benign, GCTB is clinically consequential due to its locally destructive behavior, propensity for recurrence, and rare capacity for metastasis and malignant transformation. Over the past decade, the identification of recurrent H3F3A p.G34 mutations has fundamentally reshaped the understanding of GCTB pathogenesis, establishing the stromal cell as the true neoplastic driver and positioning the tumor as a paradigmatic epigenetically driven osteolytic disease. This narrative review focus on biology, pathophysiology, and histopathology in the era of H3F3A. H3F3A-mutant stromal cells orchestrate pathological osteoclastogenesis through dysregulated RANKL signaling and chromatin reprogramming, giving rise to the characteristic cellular admixture of osteoclast-type giant cells, mononuclear histiocytic cells, and neoplastic stromal elements. The targeted inhibition of osteoclast activity with denosumab has transformed clinical management, inducing profound morphological changes and bone formation. However, its long-term impact on local control, recurrence patterns, and malignant progression remains unclear. Collectively, GCTB exemplifies a molecularly defined bone tumor in which advances in epigenetic biology and tumor–microenvironment interactions have directly influenced diagnostic practice and therapeutic strategy. Ongoing challenges include refining risk stratification, optimizing treatment sequencing, and clarifying the biological consequences of sustained osteoclast suppression. Full article

The sacrum is a common site for a wide range of pathological processes, including benign and malignant tumors as well as non-neoplastic conditions. Accurate diagnosis of sacral lesions remains challenging due to overlapping imaging features and the anatomical complexity of the region. This review provides a comprehensive overview of sacral lesions, with emphasis on imaging characteristics, diagnostic challenges, and clinical implications. Key imaging findings are highlighted to help narrow the differential diagnosis. While certain imaging patterns may suggest specific etiologies, image-guided biopsy is often necessary for definitive diagnosis. Familiarity with the spectrum of sacral pathologies is essential for radiologists to effectively contribute to diagnosis, patient management, and multidisciplinary care. Full article

Implant science has traditionally treated “biocompatibility” as the master criterion of success, focusing on cytotoxicity, corrosion, immune response, infection control, and the chemical stability of materials in vivo. However, many clinically “biocompatible” devices still fail at the point where the body actually meets the device: the mechanical interface. The interface is not a passive boundary. It is a living, adapting, mechanosensitive microenvironment in which cells integrate stiffness, micromotion, surface roughness, fluid shear, and wear debris with biochemical signals to decide whether to incorporate an implant, wall it off, resorb adjacent tissue, or trigger chronic inflammation. In load-bearing orthopaedics, stiffness mismatch produces stress shielding and maladaptive remodelling; excessive micromotion drives fibrous encapsulation rather than osseointegration; abrasive wear creates particulates that sustain macrophage activation and osteolysis; and design choices that are mechanically adequate in bench tests can still fail in vivo when the implant–tissue system evolves. In soft-tissue implantation, substrate stiffness can be a primary driver of the foreign body response and fibrotic capsule formation through mechanosensitive pathways, such as TRPV4-mediated macrophage–fibroblast signalling. Mechanical compatibility is not a replacement for classical biocompatibility; rather, it should be treated as a co-equal, first-class design requirement in mechanosensitive organisms. Chemically biocompatible materials can still fail through stiffness mismatch, micromotion, fretting and wear debris generation, and mechanobiology-driven fibrosis or osteolysis. We therefore propose a process view of implant success: tissue mechanics should be measured in clinically relevant states, transformed into constitutive models and interface performance envelopes, translated into explicit mechanical-compatibility specifications, and then realised through manufacturing process windows that can reliably reproduce targeted architectures and surface states. Additive manufacturing and microstructural engineering enable the tuning of modulus, the formation of porosity gradients, and the generation of patient-specific compliance fields, but these advances only improve outcomes when coupled to metrology, statistical process control, and validation loops that close the gap between intended and realised interface mechanics through clinical surveillance. Full article

Jawbone cavitations have been described for decades under various terminologies, including neuralgia-inducing cavitational osteonecrosis (NICO) and fatty degenerative osteolysis of the jawbone (FDOJ). Their biological nature and clinical relevance remain controversial. The present review aimed to summarize the current understanding of jawbone cavitations, identify relevant research gaps, and propose a unified descriptive terminology. This narrative literature review was conducted using PubMed/MEDLINE, Google Scholar, and manual searches of relevant journals. The available evidence was qualitatively synthesized. The results indicate that most published data on jawbone cavitations are derived from observational, retrospective, and cohort studies, with etiological concepts largely based on histopathological findings. Recent three-dimensional radiological analyses suggest that intraosseous non-mineralized areas frequently observed at former extraction sites may represent a physiological outcome of socket collapse and incomplete ossification rather than a pathological condition. This review introduces Covered Socket Residuum (CSR) as a radiological descriptive term and clearly distinguishes it from pathological entities such as NICO and FDOJ. Recognition of CSR is clinically relevant, particularly in dental implant planning, where unrecognized non-mineralized areas may compromise primary stability. The findings emphasize the role of three-dimensional radiological assessment for diagnosis and implant planning and discuss preventive and therapeutic strategies, including Guided Open Wound Healing (GOWH^TM). Prospective controlled clinical studies are required to validate this concept and determine its clinical relevance. Full article

Bone metastasis in breast cancer remains a major therapeutic challenge because current osteoclast-targeted therapies do not fully disrupt the tumor–bone vicious cycle. Osteocytes, the most abundant bone cells, are increasingly recognized as key regulators of bone–tumor crosstalk. Previous work has shown that osteocyte-specific overexpression of the Wnt co-receptor LRP5 inhibits breast cancer-induced osteolysis and generates conditioned medium (CM) with tumor-suppressive activity. Proteomic analysis identified LIM domain and actin-binding protein 1 (LIMA1) as a central mediator that interacts with Myosin Vb (MYO5B), suggesting the role of the LIMA1/MYO5B regulatory axis. This study demonstrates that CM derived from LRP5-overexpressing osteocytes suppresses EO771 breast cancer cell proliferation, migration, and invasion, and downregulates tumor-promoting proteins, including MMP9, Snail, IL-6, and TGF-β1, while upregulating the apoptosis-related protein cleaved caspase-3. These effects were largely reversed by knockdown of LIMA1 or MYO5B. In syngeneic mouse models of mammary tumors and bone metastasis, systemic administration of LRP5-overexpressing osteocyte-derived CM reduced tumor burden and osteolytic bone destruction, whereas genetic knockdown of LIMA1 in osteocytes or MYO5B in tumor cells abrogated these protective effects. Collectively, these findings indicate that LRP5 activation in osteocytes engages the LIMA1/MYO5B signaling axis that inhibits breast cancer progression and osteolysis, disrupts tumor–stromal interactions, and restores bone–tumor homeostasis, thereby providing a potential therapeutic strategy to break the vicious cycle of bone metastasis in breast cancer. Full article

Bone metastases mark a critical and often terminal phase in cancer progression, where disseminated tumor cells (DTCs) manage to infiltrate and exploit the complex microenvironments of the bone marrow. While most current therapies focus on the well-known late-stage “vicious cycle” of osteolysis, they often overlook the earlier stages, namely, tumor cell colonization and dormancy. During these early phases, cancer cells co-opt hematopoietic stem cell (HSC) niches, using them as sanctuaries for long-term survival. In this review, we bring together emerging insights that highlight a trio of underappreciated cellular players in this metastatic takeover: megakaryocytes, erythroid lineage cells, and perivascular stromal subsets. Far from being passive bystanders, these cells actively shape the metastatic niche. For instance, megakaryocytes and platelets go beyond their role in transport; they orchestrate immune evasion and dormancy through mechanisms such as transforming growth factor-β1 (TGF-β1) signaling and the physical shielding of tumor cells. In parallel, we uncover a distinct “erythroid-immune” axis: here, stress-induced CD71⁺ erythroid progenitors suppress T-cell responses via arginase-mediated nutrient depletion and checkpoint engagement, forming a potent metabolic barrier against immune attack. Furthermore, leptin receptor–positive (LepR⁺) perivascular stromal cells emerge as key structural players. These stromal subsets not only act as anchoring points for DTCs but also maintain them in protective vascular zones via CXCL12 chemokine gradients. Altogether, these findings reveal that the metastatic bone marrow niche is not static; it is a highly dynamic, multi-lineage ecosystem. By mapping these intricate cellular interactions, we argue for a paradigm shift: targeting these early and cooperative crosstalk, whether through glycoprotein-A repetitions predominant (GARP) blockade, metabolic reprogramming, or other niche-disruptive strategies, could unlock new therapeutic avenues and prevent metastatic relapse at its root. Full article

Contemporary knee prostheses rely predominantly on a metal–polyethylene bearing couple, which—despite substantial advances in material engineering—continues to generate polymeric wear particles over time. While the local biological effects of polyethylene debris, such as inflammation and osteolysis, are well-characterised, their potential systemic implications remain insufficiently explored. In this review, we synthesise multidisciplinary evidence to evaluate the generation, biological behaviour, and systemic dissemination of polyethylene-derived nano- and microplastics (NMPs) released from knee prostheses. We also contextualise prosthetic wear within the broader toxicological framework of NMP exposure, highlighting translocation pathways, interactions with immune and metabolic systems, and potential multi-organ effects reported in recent experimental and clinical studies. Current findings suggest that prosthetic wear may represent an under-recognised internal source of NMP exposure, with possible implications for long-term patient health. A clearer understanding of the systemic behaviour of prosthetic-derived NMPs is essential to guide future biomonitoring studies, improve prosthetic materials, and support the development of safer, more biocompatible implant designs. Full article