Abnormal Bone Research Articles

Sprouty2/4 deficiency disrupts early signaling centers impacting chondrogenesis in the mouse forelimb.

The FGF signaling pathway plays an important role in the regulation of limb development, controlling cell migration, proliferation, differentiation, and apoptosis. Sprouty proteins act as antagonists of the FGF pathway and control the extent of FGF signaling as part of a negative feedback loop. Sprouty2/4 deficient mice evince defects in endochondral bone formation and digit patterning in their forelimbs, with pathogenesis recently related to ciliopathies. To understand the mechanisms behind these pathologies, the limb defects in Sprouty2+/-;Sprouty4-/- male and female mice were characterized and correlated to the dynamic expression patterns of Sprouty2 and Sprouty4, and the impact on the main signaling centers of the limb bud was assessed. Sprouty2 and Sprouty4 exhibited dynamic expressions during limb development. Interestingly, despite similar expression patterns in all limbs, the hindlimbs did not evince any obvious alterations in development, while the forelimbs showed consistent phenotypes of variable severity. Prenatally as well as postnatally, the left forelimb was significantly more severely affected than the right one. A broad variety of pathologies was present in the autopodium of the forelimb, including changes in digit number, size, shape, and number of bones, hand clefts, and digit fusions. Ectopic ossification of bones and abnormal bone fusions detected in micro-CT scans were frequently observed in the digital as well as in the carpal and metacarpal areas. Sprouty2+/-;Sprouty4-/- limb buds showed patchy loss of Fgf8 expression in the apical ectodermal ridge, and a loss of tissue underlying these regions. The zone of polarizing activity was also impacted, with lineage analysis highlighting a change in the contribution of Sonic hedgehog expressing cells. These findings support the link between Sproutys and Hedgehog signaling during limb development and highlight the importance of Sprouty2 and Sprouty4 in controlling early signaling centers in the limb.

Kidney function, bone health, and vascular calcifications in patients with CKD II - IV: A 2 - 3 year prospective study with bone biopsies.

Patients with chronic kidney disease (CKD) have serum, bone, and vascular abnormalities presenting as chronic kidney disease-mineral bone disorder (CKD-MBD) syndrome. This study sought to identify the parameters with the greatest relative impact on progression of CKD-MBD abnormalities. This prospective study measured 237 parameters including serum markers, clinical variables, dual-energy X-ray absorptiometry (DXA) measurements, vascular calcifications, and histomorphometric results from bone samples obtained at baseline and after 2-3 years. Relative impact of these parameters on kidney function, bone changes, and vascular calcification were assessed using machine learning, a subset of artificial intelligence analyses. Baseline estimated glomerular filtration rate (eGFR) values ranged from 18 to 70 mL/min and declined in 52% of subjects by at least 3.3% annually during the study. These declines in eGFR were associated with changes in specific serum markers, bone quantity decreases, and bone quality alterations, but not with arterial calcifications. Arterial calcifications were associated with collagen crosslinking heterogeneity, serum phosphorus, diuretics and atorvastatin treatment, but not with kidney function. Baseline collagen crosslinking heterogeneity was an important factor impacting progression of coronary, but not aortic calcification. Baseline serum phosphorus was a factor primarily associated with progression of aortic calcification. Machine learning revealed specific bone and vascular abnormalities occurring early during loss of kidney function. Bone, vascular, blood, medication use, and other parameters were identified impacting the presence and progression of arterial calcification and altering bone quality and quantity in this understudied patient population. Serum phosphorus levels considered normal impacted progression of arterial calcification. Identification of these parameters and their relative importance enhances our understanding of CKD progression and should improve patient care.

Prenatal ultrasound phenotype of fetuses with recurrent 1q21.1 deletion and duplication syndrome.

Our study aimed to collect fetuses with recurrent 1q21.1 deletion or duplication syndrome for systematic clinical phenotype analysis to further delineate the intrauterine phenotype features of the two reciprocal syndromes. Prenatal samples, including amniotic fluid and chorionic villus samples, were obtained by amniocentesis and chorionic villus sampling at our center, respectively. In total, 43 fetuses were diagnosed with recurrent 1q21.1 deletion or duplication syndrome via array comparative genomic hybridization (array CGH) or copy number variation sequencing (CNV-seq). Prenatal clinical data, pregnancy outcomes, and individual conditions after birth were collected. In total, 20 fetuses were diagnosed with 1q21.1 deletion syndrome, and 11 had abnormal ultrasound findings. The most common ultrasound features were renal anomalies, musculoskeletal abnormalities, and increased NT. Other less common ultrasound findings encompassed neurologic abnormalities, cardiovascular defects, absence of the gallbladder, intrauterine growth retardation, and cervical cystic hygroma. On the other hand, 23 fetuses had reciprocal 1q21.1 duplication syndrome, 11 of which had abnormal ultrasound findings, mainly nasal bone abnormalities, cardiovascular defects, increased NT, and neurologic abnormalities. Our case study suggested that the prenatal clinical phenotypes of the recurrent 1q21.1 deletion syndrome and reciprocal duplication syndrome fetuses were highly diverse with incomplete penetrance. Additionally, our findings should expand the intrauterine phenotype associated with the recurrent 1q21.1 region by a series of prenatal ultrasonic anomalies in this work that were described for the first time, which might broaden knowledge of the genotype and phenotype correlation.

Chronotherapy with Cinacalcet has a striking effect on inhibition of parathyroid gland proliferation in rats with secondary hyperparathyroidism

Secondary hyperparathyroidism (sHPT) is a significant clinical complication of CKD leading to bone abnormalities and cardiovascular disease. Current treatment based on activating the parathyroid calcium-sensing receptor (CaSR) using calcimimetics such as Cinacalcet, aims to decrease plasma PTH levels and inhibit the progression of parathyroid hyperplasia. In the present study, we found significant diurnal rhythmicity of Casr, encoding the Cinacalcet drug target in hyperplastic parathyroid glands (p = 0.006). In rats with sHPT, Cinacalcet treatment timed prior to the acrophase of Casr expression (chronotherapy: Cina1) was compared with the usual timing of treatment early in the active phase (conventional: Cina2). Without Cinacalcet treatment, induction of sHPT resulted in a significant increase in parathyroid proliferation in terms of Ki-67+ cells compared to that of control rats (p = 0.001). Conventional Cinacalcet treatment (Cina2) did not significantly reduce Ki-67 index compared to untreated rats with sHPT (p = 0.09). In contrast, chronotherapy treatment (Cina1) resulted in a marked inhibition of parathyroid proliferation by Ki-67+ cells compared to untreated rats with sHPT (p = 0.0001). We found significantly reduced parathyroid Ki-67 index using chronotherapy compared to conventional timing of Cinacalcet (Cina1 vs. Cina2: 0.92±0.14% vs. 2.46±0.37%, p = 0.006). Transcriptomic analysis showed that the reduced proliferation of Cina1 was associated with downregulation of genes involved in mitotic activity, together with an increased adaptive response of energy metabolism, as evident from upregulated pathways of Oxidative phosphorylation and TCA cycle compared to the untreated uremic group. Conclusively, it is shown that the inhibitory effect of Cinacalcet on parathyroid cell proliferation is markedly impacted by the timing of administration, suggesting a possible benefit of using chronotherapy in Cinacalcet treatment of sHPT.

Radiographic, computed tomographic, and histologic characteristics of bone for clinically normal laying hens in a free-range housing system.

Laying hens are increasingly being kept in backyard flocks and considered family pets; however, diagnostic imaging characteristics of bone for clinically normal backyard hens are currently limited. This prospective, descriptive study was to describe radiographic, computed tomographic, and histologic characteristics of bone for a group of clinically normal laying hens housed in conditions comparable to those of backyard flocks. Sixteen 60-week-old Lohmann Brown laying hens were included. Hens were housed in a free-range unit with outdoor access at a university research and teaching farm. Hens were defined as clinically normal by the farm manager and a veterinary researcher in laying hen behavior and welfare. Findings from the horizontal beam, left lateral, sternal radiographs (n=16), postmortem, and whole-body CT scans (n=4) were recorded by a veterinary radiologist and a research technician. Histologic findings for sternal, femoral, and tibiotarsal bone samples (n=5) were recorded by a veterinary pathologist. The most frequent radiographic findings for the sternal carina (keel bone) were smoothly marginated concave deviations of the ventral margin and caudal section fractures. Multiple punctate mineral opacities (PMOs) were present in radiographs and CT images for all hens and were involved in the sternal carina and multiple other bones in the axial and appendicular skeleton. No bone abnormalities were identified in any histologic sections where PMOs were radiographically detected. Authors propose that PMOs are normal radiographic and CT findings in the bones of mature, laying hens and may represent temporary calcium reservoirs formed during osteoclastic activities.

May a Single Presurgical High-Field MRI Sequence Replace Standard Radiographs for TPLO Surgical Planning in Dogs?

Cranial cruciate ligament (CCL) disease causes variable stifle instability assessed by specific clinical tests. Radiographs are performed to measure the tibial plateau angle (TPA) for planning tibial plateau leveling osteotomy (TPLO) surgery. Concomitant damage to other intra-articular structures, for which clinical detection is unreliable, may occur and potentially affect the surgical outcome. Joint assessment during TPLO through instrumented inspection is therefore advised, though it increases the risk of complications. Magnetic resonance imagingoffers a noninvasive alternative, adds information about intra- and periarticular structures, and could potentially be used for TPA measurements. This prospective study aimed to (1) assess the correlation between the TPA measured with the standard presurgical radiographs and with a single sagittal intermediate-weighted fat-saturated MRI sequence and (2) compare the surgical findings with the information obtained by the MRI sequence. Twenty-one stifles were included; TPA correlation using radiographs-MRI was available for 17 stifles, and surgery-MRI comparison was available for 18 stifles. A strong significant correlation was identified between the TPA measurements on radiographs-MRI (Pearson correlation coefficient 0.923; p-value <.0001). The sensitivity and specificity of MRI to detect surgically confirmed complete versus partial CCL rupture were 85.7% and 75%, respectively; MRI identified 7 of 8 surgically confirmed injured menisci and detected abnormal signal intensity in 8 of 10 medial menisci and nine caudal cruciate ligaments reported as normal intra-operatively. The MRI additionally identified abnormal subchondral bone signals in nine stifles and muscular hyperintensity in six cases. This presurgical MRI sequence might replace standard radiographs for TPA measurements and can provide information about concomitant joint injuries with potential prognostic impact.

Clinical Case Report: Secondary syphilis in a child with no history of sexual abuse

This pediatric case report details the diagnostic and therapeutic challenges of secondary syphilis in a six-year-old child presenting with oral lesions and perianal condyloma lata. The diagnosis was confirmed through the Venereal Disease Research Laboratory (VDRL) test, and successful treatment was achieved with benzathine penicillin. The case presented significant diagnostic complexities, necessitating the evaluation of three potential transmission routes: late congenital syphilis, sexual abuse, and non-sexual transmission. Late congenital syphilis was excluded based on the absence of typical symptoms such as bone and dental abnormalities and neurosensorial deafness. Sexual abuse was thoroughly investigated and ruled out following an extensive four-month evaluation by a multidisciplinary team comprising a psychologist, nurse, social worker, and pediatric infectious disease specialist. Ultimately, non-sexual transmission, likely from an untreated family member, emerged as the most plausible cause, supported by the observation of overcrowded living conditions and inadequate hygiene practices in the child's environment. This case underscores the necessity of comprehensive diagnostic evaluations, including consideration of all possible transmission routes, in managing pediatric syphilis. Public health interventions focusing on improving living conditions and hygiene practices are essential to prevent similar cases.

Mesoporous Lanthanum-Doped Magnesium Phosphate Nanopowders Promote Healing of Critical-Size Bone Defects: An InVivo Study.

Treating severe bone deformities and abnormalities continues to be a major clinical hurdle, necessitating the adoption of suitable materials that can actively stimulate bone regeneration. Magnesium phosphate (MP) is a material that has the ability to stimulate the growth of bones. The current study involved the synthesis of mesoporous MP and lanthanum (La)-doped nanopowders using a chemical precipitation approach. The nanopowders were analyzed using several techniques, including XRD, FTIR, HR-TEM, BET, XPS, and FE-SEM. The results confirmed the nanopowders' size of less than 40 nm and the successful incorporation of La3+ ions into the MP structure. The bioactivity of the materials was assessed invitro using simulated bodily fluid (SBF) at 37°C for a duration of 14 days in a shaker incubator (50 rpm). The SEM showed that a bone-like apatite layer formed quickly on the nanopowders' surface, proving that they have unique bioactive properties. The EDX spectra confirmed the presence of Ca, P, Mg, and La elements after immersion in SBF. The MP nanopowders, both with and without La doping, demonstrated the capacity to stimulate bone formation in a rat femoral bone defect model over a 28-day duration. Radiographic and histological studies showed that the La-doped MP nanopowders greatly improved bone repair and regeneration in comparison to the La-free nanopowders. Finally, the readily producible mesoporous MP nanomaterials, especially those with increased La doping (up to 7 wt%), exhibit significant potential for the restoration of large bone defects. Hence, fabricated nanopowders have immense promise for repairing bone criterion defects.

N-acetyl-l-cysteine stimulates bone healing by recovering the age-associated degenerative complications relative to osteoblastic Wntless ablation.

Dysregulated Wnt signaling causes age-related characteristics such as oxidative stress, stem cell senescence, and abnormal bone homeostasis. Here we explored whether supplemental n-acetyl-l-cysteine (NAC) recovers the age-associated complications relative to osteoblastic Wntless (Wls) ablation and examined the possible mechanisms therein. For this work, we administered Col2.3-Cre;Wlsfl/fl mutant and littermate control (Wlsfl/fl) mice (14 weeks of age) with NAC (40 mM)-supplemented or NAC-free water for four weeks. A proportion of these mice received non-critical-sized femoral defects at 16 weeks of age. Blood, bone, and bone marrow (BM) samples were collected and adjusted for in vivo, ex vivo, and in vitro analyses. Osteoblastic Wls deletion delayed bone mass accrual and the healing of bone defects, stimulated osteoclastic activation and inflammatory factor expression, and decreased antioxidant enzyme activity in the BM. Osteoblastic Wls deletion also promoted oxidative stress, apoptosis, and senescence in BM stromal cells (BMSCs) and decreased BMSC' multipotencies. Supplementation of Wlsfl/fl mice with NAC enhanced bone mass accrual and regenerative bone healing via a Wnt signal-associated osteogenic activation. However, supplemental NAC induced new bone formation in the mutant mice by inhibiting the age-related complications of BM/BMSCs, as well as by restoring endogenous antioxidant system without any alterations in Wnt ligand secretion, hematopoiesis, and expression of osteogenic and growth factors. This study indicates that supplemental NAC protects mice against Wnt deficiency-mediated and age-associated degenerative complications. Overall, this study highlights the therapeutic potency of NAC for restoring the antioxidant system, stem cell function, and regenerative bone homeostasis in osteoblastic Wls-dispensable manner.

Iron metabolism in rheumatic diseases.

Iron is a crucial element for living organism in terms of oxygen transport, hematopoiesis, enzymatic activity, mitochondrial respiratory chain function and also immune system function. The human being has evolved a mechanism to regulate body iron. In some rheumatic diseases such as rheumatoid arthritis (RA), systemic lupus erythematous (SLE), systemic sclerosis (SSc), ankylosing spondylitis (AS), and gout, this balanced iron regulation is impaired. Altered iron homeostasis can contribute to disease progression through ROS production, fibrosis, inflammation, abnormal bone homeostasis, NETosis and cell senescence. In this review, we have focused on the iron metabolism in rheumatic disease and its role in disease progression.

Efficacy of asfotase alfa in a patient with adult-onset hypophosphatasia without obvious bone lesions: a case report with review of literature

The use of asfotase alfa, a bone-targeted recombinant alkaline phosphatase (ALP) enzyme, for the treatment of adult-onset hypophosphatasia (HPP) remains controversial, particularly in patients without evident bone abnormalities. We report the case of a 41-year-old woman with a history of Graves' disease, who presented with progressive joint pain and severe fatigue. Despite the absence of bone lesions, the patient was diagnosed with HPP based on persistently low alkaline phosphatase levels, family history, and a novel heterozygous ALPL variant (p.Ala205Thr). Functional analysis revealed a dominant-negative effect for this variant. Her symptoms significantly interfered with her daily activities owing to uncontrolled pain and loss of motor function and were so exacerbated that high doses of acetaminophen and NSAIDs were ineffective. Treatment with asfotase alfa was initiated based on multidisciplinary team consensus. Within 3 months of treatment initiation, her pain improved significantly, as indicated by reduced scores on the visual analog scale from 6.6 to 0.9, and elimination of the need for analgesics. Additionally, her grip strength increased, and her urinary phosphoethanolamine levels and serum pyridoxal 5'-phosphate/pyridoxal ratio decreased from 90.4 to 57.8 μmol/g·creatinine and from 4.6 to 0.4, respectively. These improvements have been maintained for more than 2 years. This case highlights the potential of asfotase alfa in effectively alleviating symptoms in patients with adult-onset HPP without bone lesions, emphasizing the importance of patient selection and outcome monitoring. We also discuss the key considerations for future treatment, supported by a literature review of asfotase alfa in adult patients with HPP.

Anti-inflammatory and osteoconductive multi-functional nanoparticles for the regeneration of an inflamed alveolar bone defect.

Infected alveolar bone defects pose challenging clinical issues due to disrupted intrinsic healing mechanisms. Thus, the employment of advanced biomaterials enabling the modulation of several aspects of bone regeneration is necessary. This study investigated the effect of multi-functional nanoparticles on anti-inflammatory/osteoconductive characteristics and bone repair in the context of inflamed bone abnormalities. Tannic-acid mineral nanoparticles (TMPs) were prepared by the supramolecular assembly of tannic acid with bioactive calcium and phosphate ions, which were subsequently incorporated into collagen plugs via molecular interactions. Under physiological conditions, in vitro analysis confirmed that tannic acid was dissociated and released, which significantly reduced the expression of pro-inflammatory genes in lipopolysaccharide (LPS)-activated RAW264.7 cells. Meanwhile, the bioactive ions of Ca2+ and PO43- synergistically increased the gene and protein expressions of osteogenic markers of bone marrow-derived stem cells. For in vivo studies, combined endodontic-periodontal lesions were induced in beagle dogs where the plugs were readily implanted. After 2 months of the implantation, analysis of micro-computed tomography and histomorphometry revealed that groups of dogs implanted with the plug incorporating TMPs exhibited a significant decrease in bone surface density as well as structural model index, and significant increase in the mineralized bone content, respectively, with positive OPN expression being observed in reversal lines. Notably, the profound improvement in bone regeneration relied on the concentration of TMPs in the implants, underscoring the promise of multi-functional nanoparticles for treating infected alveolar bones.

Epidemiology of Paget's disease of bone in South Korea.

Paget's disease of bone (PDB) is a chronic disorder characterized by abnormal bone remodeling, leading to enlarged and deformed bones, and commonly affecting older adults. The disease frequently involves the pelvis, skull, spine, and long bones. Despite significant geographical variations in PDB prevalence, data from Asian populations remain sparse. This study evaluates the incidence, skeletal distribution, comorbidities, and bisphosphonate use for PDB in South Korea from 2010 to 2020, using a retrospective analysis of the Korean Health Insurance Review and Assessment database. We identified 4252 patients diagnosed with PDB via ICD-10 codes (M880, M888, and M889) over the study period. The primary outcome measured was the incidence of PDB, stratified by sex and age, with secondary outcomes including anatomical site involvement, associated comorbidities, and bisphosphonate use. The mean age of patients was 56.3 ± 14.8yr, with a mean prevalence of 1.20 per 100 000 and an age-adjusted incidence ranging from 0.38 to 1.26 per 100 000 person-years. The incidence of PDB decreased in men but showed a significant increase in women, especially after 2015. The spine (23.5%) and pelvis & femur (17.0%) were the most commonly affected sites. Gastritis and gastroesophageal reflux disease (91.6%), upper respiratory infections (78.9%), and endocrine disorders (69.5%) were frequent comorbidities. Despite the established efficacy of bisphosphonates in managing PDB, only 9.8% of patients received these treatments, predominantly etidronate (3.2%) and alendronate (2.2%). This study is the first comprehensive epidemiologic assessment of PDB in South Korea, highlighting a low but increasing incidence, particularly among women. The findings underscore the need for greater clinical awareness and more proactive management strategies, especially regarding the use of bisphosphonates to improve patient outcomes.

Subtrochanteric shortening osteotomy in adult sickle cell disease patients with cemented total hip arthroplasty for hip deformities secondary to childhood osteonecrosis: is healing a challenge?

PurposeHip deformity is frequent after childhood osteonecrosis in patients with sickle cell disease (SCD). When they are adults, they present a challenge as candidates for total hip arthroplasty (THA) because of abnormal bone development, their relative youth, and also because of their disease. Performing subtrochanteric osteotomy associated with THA is technically challenging, and healing of osteotomies has never been reported in this population with frequent osteonecrotic bone, whether using cemented or uncemented arthroplasties.MethodsWe retrospectively analyzed 59 cemented THA with femoral corrective osteotomies (subtrochanteric shortening and transverse derotational osteotomy) performed on hip deformities between 1984 and 2018 in 59 sickle cell adult patients. The patient’s age at the onset of osteonecrosis was an average of 8.4 years (6 to 10 years), and at the time of the THA was 28.6 years (19 to 41 years). All the patients had a minimum followup period of six years. Endocrinopathy was frequently associated to SCD Data and consequences were evaluated on bone union. The mechanical variables, such as the length of the resected femur, limb lengthening, the location of the osteotomy site, the size of the stem bridging the osteotomy, and any complications, were also analyzed.ResultsThe average length of the resected femoral segment was 38.4 mm. The length of the femoral stem (bridging the osteotomy) was average 13 cm. The mean osteotomy union time was 10.6 months. Twenty-four osteotomies healed in six months, six in nine months, and 29 in twelve months, while five required bone grafts at nine months. The union time of the osteotomy was average 10.6 months. Complications included four cases of transient nerve palsy, and five intraoperative femur perforations. No statistically significant relationship was found between osteotomy union time and mechanical variables. The severity of endocrinopathy associated with sickle cell disease prolonged the healing time. In three cases, cement leakage into the osteotomy gap occurred without resulting in non-healing.ConclusionCemented THA, combined with a subtrochanteric femoral shortening with transverse derotational osteotomy, has a long union time but is effective for adult hip deformities of patients with sickle cell patients.

Darolutamide in Combination with Radium-223 Exhibits Synergistic Antitumor Efficacy in LNCaP Prostate Cancer Models.

Despite treatment, prostate cancer commonly progresses into castration-resistant prostate cancer (CRPC), which remains largely incurable, requiring the development of new interventions. Darolutamide is an orally administered second-generation androgen receptor inhibitor indicated for patients with non-metastatic CRPC or metastatic hormone-sensitive prostate cancer. Here, we evaluated the effect of androgen receptor (AR) inhibition by darolutamide in combination with DNA double-strand-break-inducing targeted radium-223 alpha therapy in vitro and in an intratibial LNCaP xenograft model mimicking prostate cancer metastasized to bone. The results highlight the synergistic antitumor efficacy of darolutamide in combination with radium-223 both in vitro and in vivo. This effect was most likely driven by the downregulation of genes involved in DDR signaling, which was demonstrated in vitro by a gene set enrichment analysis. The combination treatment also reduced pathological tumor-induced effects in bone by decreasing the number of osteoblasts and osteoclasts and reducing abnormal bone formation in tumor-bearing bone. Additionally, it was shown that darolutamide does not affect the uptake of radium-223 into bone tissue. These results support the investigation of darolutamide in combination with radium-223 for the treatment of patients with CRPC metastasized to bone.

Black Bone MRI vs. CT in temporal bone assessment in craniosynostosis: a radiation-free alternative.

Craniosynostoses are rare congenital craniofacial malformations, variably affected by hearing loss, often requiring repeated CT examinations to assess skull or temporal bone (TB) abnormalities. In order to avoid radiation exposure in these young patients, efforts are made to assess the skull abnormalities on MR bone imaging sequences, such as Black Bone (BB). Our aim is to compare BB, a radiation-free imaging technique, with CT for the assessment of the TB. 48 patients who underwent both BB and CT (2016-2021) in Sophia Children's Hospital, Erasmus MC, Rotterdam, were retrospectively investigated. BB and CT (the diagnostic gold standard for imaging the temporal bone) were evaluated blindly and independently by 3 observers; visibility and abnormalities of TB structures and cranial nerves were scored; abnormal findings were confirmed by a senior pediatric neuroradiologist. The statistical analysis was performed using Gwet's AC1 agreement and modified versions of the Wilcoxon signed-rank test and sign test with a Bonferroni-Holm correction (p < 0.05). CT was rated higher than BB in structure visibility (global p = 0.0002), but was rated similar to BB when assessing TB anatomy and pathology (global p = 0.58). The visibility ratings showed better interobserver agreement values on CT than BB. In the normal/abnormal ratings, both BB (0.75-1) and CT (0.88-1) showed high interobserver agreement values. Our preliminary results suggest that BB is a promising tool for screening TB pathology in patients with craniosynostosis who require MR imaging.

Roles of osteoclasts in pathological conditions.

Bone is a unique organ crucial for locomotion, mineral metabolism, and hematopoiesis. It maintains homeostasis through a balance between bone formation by osteoblasts and bone resorption by osteoclasts, which is regulated by the basic multicellular unit (BMU). Abnormal bone metabolism arises from an imbalance in the BMU. Osteoclasts, derived from the monocyte-macrophage lineage, are regulated by the RANKL-RANK-OPG system, which is a key factor in osteoclast differentiation. RANKL activates osteoclasts through its receptor RANK, while OPG acts as a decoy receptor that inhibits RANKL. In trabecular bone, high turnover involves rapid bone formation and resorption, influenced by conditions such as malignancy and inflammatory cytokines that increase RANKL expression. Cortical bone remodeling, regulated by aged osteocytes expressing RANKL, is less understood, despite ongoing research into how Rett syndrome, characterized by MeCP2 abnormalities, affects RANKL expression. Balancing trabecular and cortical bone involves mechanisms that preserve cortical bone, despite overall bone mass reduction due to aging or oxidative stress. Research into genes like sFRP4, which modulates bone mass, highlights the complex regulation by BMUs. The roles of the RANKL-RANK-OPG system extend beyond bone, affecting processes such as aortic valve formation and temperature regulation, which highlight the interconnected nature of biological research.

Acute compartment syndrome with dorsalis pedis artery rupture after an acute ankle inversion trauma

Acute compartment syndrome in lower limbs is commonly seen in fractures, crash injuries, vascular impairment, and rarely due to ankle sprain. We report a case of a 16-year-old male who was admitted to the emergency room after a traumatic lateral ankle inversion. Significant swelling and moderate pain were present at admission. Plain radiographs showed no bone abnormality. After 60 minutes, the classic signs and symptoms of acute compartment syndrome began, with no response to painkillers. Doppler ultrasound revealed arteries occlusion distal to the superior portion of the extensors retinaculum of the ankle. Anterior foot and ankle fasciotomy were performed, with an angiography revealing a dorsalis pedis artery rupture; both ends were ligated intraoperatively. Postoperative flow was observed through the local collateral system.Level of Evidence IV; Therapeutic Studies; Case Report

A Rare Bond: Exploring the Heart-Hand Connection in Holt-Oram Syndrome

Holt-Oram syndrome is an autosomal dominant disorder characterized by upper limb abnormalities in association with congenital heart lesions. We present you a 42 years old female having ostium secundum atrial septal defect (OS-ASD) and congenital upper limb deformity. Her X-ray of hands showed bilateral abnormal carpal bones with underdeveloped thumb. This study highlights the importance of recognizing the heart-hand connection in Holt-Oram syndrome and presents the need for multidisciplinary care and early intervention.

A Taybi-Linder syndrome-related RTTN variant impedes neural rosette formation in human cortical organoids.

Taybi-Linder syndrome (TALS) is a rare autosomal recessive disorder characterized by severe microcephaly with abnormal gyral pattern, severe growth retardation and bone abnormalities. It is caused by pathogenic variants in the RNU4ATAC gene. Its transcript, the small nuclear RNA U4atac, is involved in the excision of ~850 minor introns. Here, we report a patient presenting with TALS features but no pathogenic variants were found in RNU4ATAC, instead the homozygous RTTN c.2953A>G variant was detected by whole-exome sequencing. After deciphering the impact of the variant on the RTTN protein function at centrosome in engineered RTTN-depleted RPE1 cells and patient fibroblasts, we analysed neuronal stem cells (NSC) derived from CRISPR/Cas9-edited induced pluripotent stem cells and revealed major cell cycle and mitotic abnormalities, leading to aneuploidy, cell cycle arrest and cell death. In cortical organoids, we discovered an additional function of RTTN in the self-organisation of NSC into neural rosettes, by observing delayed apico-basal polarization of NSC. Altogether, these defects resulted to a marked delay of rosette formation in RTTN-mutated organoids, thus impeding their overall growth and shedding light on mechanisms leading to microcephaly.