Search Results (410)

Background: Mucopolysaccharidosis type II (MPS II) is a progressive, rare, X-linked inherited disease with multi-organ involvement and a restricted life expectancy. The disease has two main forms: neuronopathic (severe) and non-neuronopathic (attenuated). Aim: To compare the two main forms of MPS II to identify signs for early recognition of severe disease forms in daily practice. Methods: In this retrospective cohort study, clinical and laboratory data, as well as enzyme replacement therapy data, for approximately 162 patients were extracted and analyzed from the Russian MPS II registry. Patients with insufficient clinical information (23 patients) and children under 5 years of age (15 patients) were excluded. We compared patients with MPS II neuronopathic (n = 82, 66.1%) and non-neuronopathic forms (n = 42, 33.9%) based on the presence of cognitive deficits after age 6 years and on remaining committed to the phenotype throughout follow-up. Results: The patients with both forms had the following symptoms with similar frequency: Hurler phenotype, hernias, hepatosplenomegaly, short neck, orthopedic problems: spinal pathology (curvature), chest deformity, joint stiffness, deformity of the hand, hand contractures, wrist joint deformity and contractures, elbow joint deformity and contractures, shoulder and knee deformity and contractures, hip contractures, cardiomyopathy, obstructive respiratory tract diseases, noisy breathing, hearing loss, carpal tunnel syndrome. Highly specific symptoms (frequency of occurrence above 80%) for the diagnosis of the neuronopathic form of MPS II were: delayed intellectual disability at the age of 1–3 years, epilepsy, and the presence of gross rearrangements in the IDS gene. Highly sensitive symptoms (above 80%) were: psychomotor development delay of up to 1 year of age and delayed intellectual disability at the ages of 1–3 years, heart damage, and myxomatous degeneration of the valves (79.5%). A symptom with high sensitivity and specificity is delayed mental and speech development between the ages of one and three, with respective sensitivities and specificities of 94.8 and 86.5. Conclusions: Identifying symptoms characteristic of neuronopathic forms of MPS is important not only for determining the clinical form of the disease but also for developing various approaches to treating such patients. Early diagnosis of severe forms of MPS II will make it possible to use currently approved methods of intraventricular enzyme replacement therapy, or primarily use of ERT capable of crossing the brain-blood barrier which could improve the prognosis for such patients. Symptoms that predict the risk of developing the neuronopathic form can be used in clinical practice. Full article

Background and clinical significance:Pasteurella spp. are Gram-negative coccobacilli, aerobic facultatively anaerobic, belonging to the Pasteurellaceae family. In humans, they are known to cause zoonotic diseases, which usually develop after dog or cat bites, licks or scratches. Case presentation: We present the case of a 61-year-old patient, with cardiovascular comorbidities, who presented to the Orthopedics Department, 38 days after knee replacement surgery, with recurrence of pain on walking, an antalgic gait with auxiliary support, and local signs of inflammation at the level of the left knee joint. The patient admitted to owning a dog who accidentally licked the post-surgical wound. The symptoms were suggestive of a post-surgical wound infection with extension to the periprosthetic area. A purulent discharge was collected from the wound during surgical debridement and sent to the microbiological laboratory for diagnosis, where Pasteurella canis was identified using MALDI-TOF MS. Antibiotic susceptibility testing (AST) was performed according to the EUCAST guidelines and empiric antibiotic treatment was started with Cefuroxime. During his future admissions to the Orthopedics and Infectious Diseases departments, two more samples were collected, in which Pasteurella canis was isolated, along with Klebsiella oxytoca (second sample), and Klebsiella oxytoca and Pseudomonas aeruginosa (third sample). Patient evolution was favorable due to the debridement of the wound and combined antibiotic treatment, with Ceftazidime and Gentamicin. Conclusions: Infections with Pasteurella canis are rare but slowly increasing due to more and more humans owning pets. The present case underlines the importance of interdisciplinary collaborations when rare pathogens are identified. Full article

The world population is aging at an accelerating pace, and the rate of disability caused by chronic diseases and trauma is on the rise. The traditional rehabilitation model has some structural defects, such as subjective evaluation, homogeneity in treatment schemes, imbalance of resource allocation, and insufficient intervention accuracy. The deep integration of big data analysis, artificial intelligence (AI), edge computing, digital twins, federated learning and multimodal large models is promoting a shift in the rehabilitation system from an experience-driven paradigm to a data-driven paradigm. This review systematically summarizes the development and evolution of big data analysis and artificial intelligence pertaining to intelligent rehabilitation, proposes a four-tier progressive technical architecture, summarizes the standardized governance paradigm of heterogeneous rehabilitation big data, and analyzes the mechanism and application boundaries of artificial intelligence algorithms in rehabilitation scenarios, such as neurology, orthopedics, elderly balance, and speech cognition. By comparing typical intelligent rehabilitation platforms horizontally, the core bottlenecks, including data islands, lack of clinical interpretability, weak robustness in complex environments and lack of evidence-based support, were identified. A future development path for integrating federated learning, lightweight multimodal models, human digital twins, flexible wearable sensing and other technologies is proposed to provide theoretical support for the next generation of rehabilitation systems. Full article

Diabetes mellitus is increasingly recognized as a disorder of skeletal quality in addition to metabolic dysregulation. Both type 1 and type 2 diabetes are associated with increased fracture risk, impaired fracture healing, and higher rates of orthopedic complications despite preserved or even elevated bone mineral density, highlighting the limitations of conventional densitometric assessment alone. Diabetic bone disease arises through complex and interconnected mechanisms involving osteoblast, osteocyte, and osteoclast dysfunction, accumulation of advanced glycation end products, oxidative stress, chronic inflammation, impaired insulin and insulin-like growth factor-1 signaling, and disruption of bone–pancreas and bone–adipose crosstalk. Here, we review the cellular, molecular, genetic, and epigenetic mechanisms that contribute to diabetic skeletal fragility and examine how these abnormalities impair bone remodeling, fracture healing, and orthopedic outcomes. Particular emphasis is placed on the disconnect between bone mineral density and bone quality, describing how alterations in bone microarchitecture and matrix integrity contribute to skeletal fragility beyond the conventional measures of bone mass. We further review emerging strategies for fracture risk assessment, including advanced imaging modalities and biomarkers that more accurately characterize diabetic bone disease, and discuss the influence of antidiabetic therapies, perioperative glycemic optimization, and emerging biologic and epigenetic therapeutic approaches on fracture healing and musculoskeletal outcomes. By integrating molecular mechanisms with clinical and orthopedic evidence, this review provides a comprehensive overview of diabetic bone disease while highlighting priorities for future research and clinical translation. Full article

Balancing thrombotic and bleeding risk remains the central challenge of anticoagulation, and clinically significant bleeding continues to limit even direct oral anticoagulants, especially in high-bleeding-risk patients. Factor XI (FXI) and activated FXI (FXIa) inhibitors are a mechanistically novel class that seeks to uncouple thrombosis from hemostasis; FXI amplifies clot formation through the intrinsic pathway but contributes little to physiologic hemostasis. This state-of-the-art review examines three classes of FXI/FXIa inhibitors (antisense oligonucleotides, monoclonal antibodies, and small-molecule inhibitors) that are in advanced phase II and III clinical trials, and synthesizes currently available evidence across six indications, including primary thromboprophylaxis in high-bleed-risk orthopedic surgery, primary thromboprophylaxis in end-stage renal disease, stroke prevention in atrial fibrillation, acute coronary syndromes, secondary stroke prevention, and treatment of cancer-associated venous thromboembolism. A pattern emerges, where FXI/FXIa inhibition offers a favorable safety profile across multiple settings and high-risk subgroups, yet clear efficacy has so far been established only in secondary prevention of noncardioembolic ischemic stroke over existing antiplatelet strategies. Although unlikely to completely replace current anticoagulants, these agents may offer important therapeutic options for selected high-risk populations. Ongoing phase II and III trials will further define their potential advantages in areas of unmet clinical need. Full article

Neuro-orthopedics is a field comprising knowledge and methods aimed at the diagnosis and treatment of secondary musculoskeletal disorders resulting from primary nervous system pathology. Historically, the greatest step in its development was associated with overcoming the consequences of the polio epidemic, which marked the “early spring” of pediatric orthopedics. However, for progressive neuromuscular diseases like spinal muscular atrophy (SMA), extrapolation of principles developed for poliomyelitis and cerebral palsy did not produce the desired results, leading to a “late autumn” stage, where aggressive surgical intervention was deemed inappropriate, with surgery only recommended as a palliative for intractable pain or care issues. The advent of disease-modifying therapy for SMA opened a new era. Although patients now survive longer, those with SMA type 1 often do not achieve independent standing or walking, predisposing them to hip subluxation and dislocation. Hip joint pathology in neuro-orthopedic diseases remains a significant clinical challenge; however, no unified terminology exists, and neurogenic hip dislocation differs from DDH in being acquired and progressive, requiring dynamic surveillance rather than a one-time assessment. Comparison of current practices across conditions (DDH, CP, myelomeningocele, arthrogryposis, and SMA) reveals heterogeneous diagnostic criteria, screening protocols, and treatment goals. The migration percentage, used in CP, may be an important criterion, but the threshold may differ. Despite a decade of experience with targeted therapy, no significant prospective comparative clinical study has evaluated reconstructive hip surgery outcomes in SMA. Thus, direct application of principles from other conditions is unlikely to resolve the uncertainty. Residual motor function, as in MMC, the migration percentage, contractures, and upper-limb function should be considered. The challenge parallels the “early spring” era, when thousands of polio survivors needed care. We must design fundamentally new frameworks for solving secondary problems after patients have received a chance at life. International, interdisciplinary, integrative research is urgently needed to define diagnosis, screening, prevention, and surgical indications for hip instability in SMA in the DMT era. Full article

Bone defects from trauma, tumor resection, infection, and degenerative disease remain a large clinical problem, and the grafting strategies used to treat them still carry familiar limitations: donor-site morbidity for autografts, variable integration and supply constraints for allografts. Synthetic substitutes have narrowed the gap but rarely combine mechanical competence with biological activity in a single material. Zirconium dioxide (ZrO₂) has been used in orthopedics and dentistry for decades on the strength of its fracture toughness, which derives from the stress-induced tetragonal-to-monoclinic transformation, together with chemical stability and an established safety record. At the nanoscale, ZrO₂ can provide functionalities beyond mechanical reinforcement in appropriately engineered systems. Its high surface area, tunable surface chemistry, and potential mesoporosity have been exploited in selected formulations for matrix reinforcement, surface-mediated cellular interactions, therapeutic cargo loading and release, and antibacterial applications. This review covers the physicochemical basis of ZrO₂ behavior, including crystal phases, transformation toughening, surface chemistry and hydrothermal stability, and the influence of synthesis route on particle size and dispersion, and links these to protein adsorption, osteoblast response, osteogenic signaling, and immunomodulatory and antibacterial effects. Recent applications are surveyed across scaffold reinforcement, bone cements and fillers, implant surface modification, local drug delivery, and infection control. Recurring issues are examined throughout, including the reported loading ranges associated with mechanical performance and the effects of particle agglomeration, the confounding effect of porosity on reported strength, and the need to pair ZrO₂’s bioinertness with bioactive phases. The review closes with cytotoxicity, long-term particle fate, scale-up and regulatory barriers, and prospects in additive manufacturing, personalized grafts, and theragnostic design. Full article

Background: Metabolic bone diseases represent prevalent global disorders characterized by disrupted bone homeostasis and chronic inflammation. This review utilizes a broad working definition encompassing osteoporosis and other classic metabolic bone disorders, including osteoarthritis, a primarily degenerative joint disease marked by significant metabolic-driven subchondral bone remodeling. Conventional diagnostic modalities prove inadequate for early-stage disease screening, while classical pharmacological interventions face limitations due to unsatisfactory targeting performance and severe long-term adverse reactions. An urgent clinical need persists for innovative diagnostic biomarkers and targeted therapeutic strategies. Exosomes, a sub-population of small extracellular vesicles (sEVs), are natural nanoscale intercellular vesicles derived from multivesicular bodies, playing critical regulatory roles in bone metabolism and offering substantial clinical translational potential. This review systematically elaborates the regulatory networks associated with exosomes, the biomarker potential of exosomal non-coding RNAs, and advanced engineering modifications for bone-targeted delivery in metabolic bone diseases. Methods: This narrative review involved a literature search conducted across PubMed, Web of Science, Scopus, and Embase from inception to December 2025, focusing on exosome biology, metabolic bone disorders, non-coding RNA biomarkers, and engineered bone-targeted delivery. Inclusion criteria encompassed peer-reviewed English original and review articles, while conference abstracts, case reports, editorials, and non-English literature were excluded. Eighty-two eligible studies underwent thematic analysis without a formal systematic search protocol or preregistration. Results: Exosomes orchestrate osteogenic and osteoclastogenic processes through established bone-metabolic signaling cascades. Exosomal microRNAs and circular RNAs demonstrate promising diagnostic performance in exploratory observational cohorts for early-stage screening and prognostic assessment of metabolic bone diseases; however, large-scale multi-center clinical validation remains insufficient. Engineered exosomes facilitate precise local bone intervention in preclinical animal models, overcoming significant drawbacks of conventional therapies in experimental settings. Nevertheless, clinical translation is obstructed by non-standardized production workflows and unresolved biosafety risks. Conclusions: Exosomes present promising dual diagnostic and therapeutic potential to enhance precision and individualized management of metabolic bone diseases. Further technical refinement in exosome preparation and modification will expedite orthopedic clinical translation and improve patient outcomes in metabolic bone disorders. Full article

Bone adhesives have long been pursued in orthopedic and regenerative medicine, but their clinical translation remains limited, particularly in wet and mechanically demanding environments. This PRISMA-guided systematic review analyzes bioadhesive biomaterials and adhesive regenerative platforms for bone regeneration, focusing on material composition, adhesion mechanisms, fabrication strategies, biological performance, and translational limitations. Current evidence shows a clear shift from passive adhesive systems toward multifunctional regenerative platforms that combine wet adhesion with osteogenic, angiogenic, immunomodulatory, antimicrobial, and controlled-release functions. Hybrid polymer networks, catechol-mediated chemistry, Schiff-base reactions, dynamic crosslinking, and nanocomposite or ion-releasing strategies emerge as dominant design approaches. However, adhesion testing remains highly heterogeneous, with lap shear, tensile, peel, and related assays performed under variable dry, wet, or pseudo-physiological conditions, limiting cross-study comparison and benchmarking against clinical standards. In vivo evidence is mainly concentrated in small-animal, non-load-bearing defect models, whereas large-animal validation, load-relevant testing, long-term safety data, and disease-specific models remain scarce. Overall, the main translational bottleneck appears to lie not only in adhesive chemistry, but also in the absence of standardized, bone-specific, and mechanically relevant interfacial performance metrics. This review provides an integrated perspective linking adhesion mechanics, biological function, and translational readiness to guide the future development of bioadhesive biomaterials for bone regeneration. Full article

Background: Acute compartment syndrome (ACS) is a critical orthopedic emergency where increased pressure in a limb compartment leads to muscle ischemia, necrosis, and lasting dysfunction. While fasciotomy is the standard treatment, it often results in complications like infection and nerve damage, underscoring the need for effective non-surgical therapies to manage the inflammation causing tissue damage. Peripheral nerve block (PNB) with ropivacaine is clinically used for analgesia, but whether it can serve as a disease-modifying adjunct intervention for ACS beyond pain control remains unexplored. Objective: This study examined the potential of PNB utilizing ropivacaine to enhance outcomes in ACS and explored the underlying mechanisms related to macrophage polarization. We aimed to distinguish two unresolved questions: (1) whether ropivacaine-based PNB confers tissue-protective effects in ACS independent of analgesia; (2) what signaling pathway mediates ropivacaine-driven macrophage phenotypic switch under ACS-relevant inflammatory conditions. Methods: Using rats, an ACS model was established, with the animals being randomly allocated to five different groups: Control, ACS, sciatic PNB, femoral PNB, and combined PNB. The study assessed functional outcomes, histopathological changes, levels of inflammatory markers (interleukin-6 (IL-6), C-reactive protein (CRP), and markers of macrophage polarization (CD86, CD206). In parallel, RAW264.7 macrophages stimulated with LPS and IFN-γ were treated with ropivacaine (1–10 μg/mL), and M1/M2 markers, pro-inflammatory cytokines (TNF-α, IL-6, IL-1β), migratory capacity, and cytotoxicity were assessed. Differentially expressed genes and enriched pathways were identified through RNA sequencing, followed by mechanistic validation of JAK-STAT signaling using Western blotting, immunofluorescence, immunohistochemistry, and rescue experiments with the JAK2 inhibitor AG490. Results: PNB significantly improved all functional and histological parameters in ACS rats, with combined blockade demonstrating the greatest efficacy. Ropivacaine at 5 μg/mL promoted M2 macrophage polarization, evidenced by upregulated CD206 and arginase-1 alongside downregulated CD86 and iNOS, while reducing pro-inflammatory cytokine production without cytotoxicity. Ropivacaine also suppressed macrophage migration. Among 83 differentially expressed genes, RNA sequencing pinpointed JAK-STAT as the pathway with the highest level of enrichment. Mechanistically, ropivacaine activated JAK2-STAT3, reflected by increased p-JAK2/JAK2 and p-STAT3/STAT3 ratios. AG490 completely reversed ropivacaine-induced JAK-STAT activation, M2 polarization, cytokine suppression, and migratory inhibition in vitro, and similarly abrogated PNB-mediated functional recovery and histological protection in vivo. Conclusions: In vitro, ropivacaine directly promoted macrophage M2 polarization via JAK-STAT activation. In vivo, ropivacaine-based PNB ameliorates ACS, which may involve both direct immunomodulatory effects of ropivacaine and indirect biological consequences of peripheral neural blockade. This study provides the first pre-clinical proof-of-concept that ropivacaine PNB can act as an adjunctive disease-modifying strategy for ACS (beyond analgesia), and identifies macrophage JAK2-STAT3 as the critical molecular cascade responsible for this immunomodulatory effect. This identifies a readily translatable adjunctive strategy for ACS and establishes JAK-STAT as a potential pharmacological target for compartment syndrome-associated inflammation. Full article

Stem cell transplantation represents a promising approach to regenerative medical therapies for many disorders, including neurodegenerative, rheumatologic, digestive, orthopedic, hematologic and cardiovascular diseases. In the case of stem cell therapy for ischemic cardiomyopathy, this promise has been blunted by a lack of understanding of critical factors governing regeneration of adult human heart muscle. This review aims to (1) summarize the characteristics and types of stem cells used to treat cardiomyopathies; (2) to survey the results of clinical trials conducted with stem cells used to treat cardiomyopathies; and (3) to understand limitations of and obstacles to effective stem cell therapies for cardiomyopathies. Stem cells contribute both constitutive and paracrine functions, exemplified by their ability to replace damaged and destroyed cells and to secrete cytokines and chemokines, respectively. Cardiac regenerative capacity, while high in most fish, amphibians and newborn mammals, is extremely limited in adult mammals. Alterations in physiologic functions necessary to prevent destructive oxidation in endotherms forced a trade-off with tissue regenerative capacity in these animals. A review of 15 stem cell trials for ischemic cardiomyopathies supports conclusions based on these considerations and underscores the need to maximize stem cell delivery efficiency. Experimental approaches to achieve this objective are reviewed. Full article

Osteogenesis imperfecta (OI) is the most common heritable bone-fragility disorder, with type I (non-deforming OI) representing its mildest classical phenotype (historically referred to as Lobstein disease). Intramedullary (IM) rodding is essential for managing recurrent long-bone fractures and progressive deformities, with the Fassier–Duval (FD) telescopic rod now being the standard choice. This narrative review, based on a structured search from the seminal 1959 description of IM rodding to 2026, synthesizes the design principles, the minimally invasive technique and the comparative outcomes of FD rodding of the lower limb, with explicit attention to type I disease. Across cohort studies, comparative series and a recent systematic review, telescopic rods consistently achieve lower revision rates and longer implant survival than static or non-telescopic devices, reducing reoperation odds by roughly three-quarters. Overall complication rates nonetheless remain high (commonly 33–55%) and are dominated by implant migration and failure of telescoping. Younger age and eccentric epiphyseal positioning after incomplete deformity correction increase migration risk. Type-I-specific evidence remains limited. A report published under the “Lobstein” designation involved a Sillence type IV patient and therefore does not constitute type-I-specific evidence. Retrospective data nevertheless suggest favorable implant survival with telescopic fixation, but definitive conclusions cannot yet be drawn. Proper technique, adjunctive bisphosphonate therapy and multidisciplinary care remain decisive. Phenotype-stratified prospective data are the principal unmet need. Full article

Background/Objectives: Surgical indications for spondylodiscitis are controversial, particularly when epidural extension and evolving neurological compromise are present. This study aimed to describe the clinical, neurological, pain-related, and inflammatory outcomes of patients with spondylodiscitis treated with decompressive laminectomy without spinal stabilization, at a single tertiary center. Methods: We retrospectively reviewed 15 consecutive patients with spondylodiscitis who underwent decompressive laminectomy at the University Hospital of Trieste between January 2017 and December 2023. Inclusion required at least 6 months of clinical and laboratory follow-up. Patients treated with acute vertebral stabilization were excluded. Collected data included spinal level, timing from diagnosis to surgery, visual analog scale (VAS) pain score, Cooper Scale grade, modified Japanese Orthopedic Association score (mJOA), white blood cell count, and C-reactive protein (CRP). Assessments were performed preoperatively (T0), 1 week after surgery (T1), and at 6 months (T2). Imaging findings from representative cases were reviewed to illustrate the radiographic evolution after decompression combined with antibiotic therapy and orthotic support. Results: The cohort included 8 women and 7 men with a mean age of 57.33 years. Twelve patients (80%) underwent surgery within 48 h because of neurological deterioration or urgent compressive findings. Thoracic involvement was predominant (11 cases, 73%), whereas cervical and lumbar disease accounted for 1 and 3 cases, respectively. Intraoperative cultures were positive in 9 patients (60%), and Staphylococcus aureus was isolated in 7 of these 9 cases (77.8%). Mean VAS pain score improved from 6.3 at T0 to 4.3 at T1 and 1.4 at T2. Mean lower-extremity Cooper Scale grade improved from 2.7 to 2.1 to 0.6; mean upper-extremity Cooper Scale grade improved from 1.3 to 1.0 to 0. Mean mJOA improved from 10.3 to 11.4 to 16.0. Mean white blood cell count declined from 11.58 to 8.35 to 6.14 × 10³/µL, and mean CRP declined from 123.9 to 72.81 to 19.44 mg/L. No patient worsened neurologically after surgery. No patient required acute stabilization or delayed arthrodesis during follow-up. Conclusions: In our case series of patients with compressive or progressive neurological spondylodiscitis, decompressive laminectomy combined with antibiotic treatment, bracing, and rehabilitation was associated with early neurological stabilization, substantial pain relief, and marked reduction in inflammatory markers, without subsequent need for instrumented stabilization. These data support the role of spinal decompression as part of a personalized, effective treatment strategy in patients with neurological decline. Full article

Background/Objectives: Achondroplasia is the most common genetic skeletal dysplasia associated with disproportionate short stature and is primarily caused by gain-of-function variants in the fibroblast growth factor receptor 3 (FGFR3) gene. Constitutive FGFR3 activation disrupts growth plate homeostasis and endochondral ossification through complex alterations in chondrocyte proliferation, differentiation, hypertrophy, extracellular matrix organization, and intracellular signaling. The increasing understanding of these mechanisms has enabled the transition from exclusively supportive management toward disease-modifying and precision-based therapeutic strategies. This narrative review aimed to critically synthesize current evidence on the genetic basis, molecular pathogenesis, growth plate abnormalities, and current and emerging targeted therapies in achondroplasia. Methods: A narrative literature review was conducted using PubMed/MEDLINE, Scopus, and Web of Science Core Collection, with Google Scholar used as a supplementary source, together with manual screening of the reference lists of relevant original studies, clinical trials, reviews, consensus documents, and clinical guidelines. The principal literature search covered publications from January 2010 to March 2026, while selected seminal primary studies published before 2010 were included when necessary to document the original identification of pathogenic FGFR3 variants and foundational mechanisms of FGFR3-mediated growth plate regulation. Particular emphasis was placed on FGFR3 variants, receptor activation mechanisms, growth plate dysfunction, intracellular signaling pathways, vosoritide, C-type natriuretic peptide-based therapies, FGFR3 inhibitors, ligand–receptor blockade, drug repurposing, Wnt/β-catenin modulation, and gene-based therapeutic approaches. Results: Achondroplasia is characterized by marked molecular homogeneity, with the recurrent p.Gly380Arg substitution accounting for most cases. Mutant FGFR3 displays sustained activity through partial ligand independence, enhanced receptor dimerization and kinase activation, increased receptor stability, and reduced degradation. Excessive signaling through MAPK/ERK, STAT, PI3K/AKT, IHH/PTHrP, and related pathways impairs chondrocyte proliferation and hypertrophic differentiation, alters extracellular matrix turnover, disrupts primary cilium function, and reduces longitudinal bone growth. Vosoritide provides clinical proof that pharmacological modulation of FGFR3-related signaling can improve growth velocity. Additional therapeutic strategies under clinical or preclinical investigation include long-acting CNP analogues, selective FGFR inhibitors, decoy receptors, RNA aptamers, repurposed drugs, Wnt/DKK1 pathway modulation, and gene- or enhancer-targeted interventions. Conclusions: Achondroplasia is increasingly understood as a disorder of dysregulated growth plate signaling rather than solely a condition of reduced stature. Although vosoritide has established the feasibility of disease-modifying treatment, substantial uncertainty remains regarding final adult height, skeletal proportionality, cranio-spinal development, orthopedic outcomes, and long-term safety. Future progress will depend on mechanistically informed therapeutic combinations, improved biomarkers, advanced cellular and animal models, and long-term clinical and real-world evidence. Full article

Background/Objectives: Bone is the third most common site of solid-tumor metastasis, and surgical management spans a wide spectrum from observation to curative en bloc resection in selected patients. 18F-FDG PET/CT has been reported to alter oncologic management in 20% to 45% of patients across diverse settings, yet its specific impact on surgical decision-making within a multidisciplinary orthopedic oncology board (MOOB) reassessment and the predictors of decision change remain undefined. Methods: We retrospectively analyzed consecutive patients with histopathologically confirmed bone metastases evaluated at a tertiary-care MOOB between February 2023 and February 2026. For each patient, the surgical plan was recorded twice: first by the orthopedic team based on available conventional imaging (radiography, computed tomography, magnetic resonance imaging) and then as the final PET/CT-informed MOOB review. This design evaluates changes in decision-making intent after PET/CT-informed multidisciplinary reassessment, rather than the isolated causal effect of PET/CT or actual surgical implementation. Surgical plans were categorized as no surgery, palliative stabilization, palliative resection, or curative-intent resection, and changes were classified as no change, escalation, de-escalation, or cancellation. Results: Among 73 patients (mean age 64.7 ± 12.1 years; 53.4% male), the most frequent primaries were lung (37.0%), breast (21.9%), and renal cell carcinoma (13.7%). Following PET/CT-informed MOOB reassessment, the intended surgical plan changed in 53.4% of cases (p < 0.001), comprising surgery cancellation (27.4%), escalation (17.8%), and de-escalation (8.2%). Patients directed to no surgery increased fourfold (6.8% to 28.8%), and curative resection emerged as a post-reassessment recommendation (0% to 10.9%). SUVmax did not predict overall decision change, but higher SUVmax was associated with cancellation/de-escalation in the directional analysis. In exploratory multivariable analysis, polymetastatic disease (OR 0.051; 95% CI 0.005 to 0.547; p = 0.014), long-bone diaphyseal location (OR 0.133; p = 0.006), and higher Eastern Cooperative Oncology Group (ECOG) performance score (OR 2.109 per point; p = 0.018) independently predicted decision change. Conclusions: PET/CT-informed MOOB reassessment was associated with substantial changes in intended surgical strategy for metastatic bone disease. The findings support careful multidisciplinary integration of metabolic imaging, metastatic burden, anatomic location, and performance status, but should be regarded as hypothesis-generating until validated prospectively with data on treatment delivery and downstream outcomes. Full article