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The aim of this study was to present the long-term course of a patient with nevus sebaceous syndrome (NSS). Recent genetic studies place the syndrome in the emerging group of so-called RASopathies. The focus of the report is on surgical treatment and morphological and genetic findings of the face and oral cavity. A female patient was treated for congenital alterations of facial skin and oral mucosa. The oral lesions were removed repeatedly. Eruption of teeth on the lesion sites was made easier by the measures taken. However, after repeated ablation of the affected gingiva, the periodontal papillomatous epithelium re-differentiated into the same reddish, conspicuous, hyperplastic epithelium. The teeth in the affected region showed noticeable changes in position, surface, and shape. A HRAS mutation was detected only in the regions of altered oral epithelia and not in adjacent soft tissues. Reports on NSS rarely address oral manifestations. The recorded alterations of oral soft and hard tissues in NSS indicate a topographical relationship between the development of oral mucosa and teeth as well as the long-lasting impact of a sporadic mutation on organ development at this site.

Coffin–Lowry–Syndrome (CLS) is a X-linked mental retardation characterized by skeletal dysplasia and premature tooth loss. We and others have previously demonstrated that the ribosomal S6 kinase RSK2, mutated in CLS, is essential for bone and cementum formation; however, it remains to be established whether RSK2 plays also a role in mechanically induced bone remodeling during orthodontic tooth movement (OTM). We, therefore, performed OTM in wild-type (WT) mice and Rsk2-deficient mice using Nitinol tension springs that were fixed between the upper left molars and the incisors. The untreated contralateral molars served as internal controls. After 12 days of OTM, the jaws were removed and examined by micro-computed tomography (µCT), decalcified histology, and immunohistochemistry. Our analysis of the untreated teeth confirmed that the periodontal phenotype of Rsk2-deficient mice is characterized by alveolar bone loss and hypoplasia of root cementum. Quantification of OTM using µCT revealed that OTM was more than two-fold faster in Rsk2-deficient mice as compared to WT. We also observed that OTM caused alveolar bone loss and root resorptions in WT and Rsk2-deficient mice. However, quantification of these orthodontic side effects revealed no differences between WT and Rsk2-deficient mice. Taken together, Rsk2 loss-of-function accelerates OTM in mice without causing more side effects.

PurposeSurgical intervention with intercorporal stabilisation in spinal infections is increasingly needed. Our aim was to compare titanium and polyetheretherketon (PEEK) cages according to their adhesion characteristics of different bacteria species in vitro. MethodsPlates made from PEEK, polished titanium (Ti), two-surface-titanium (TiMe) (n = 2–3) and original PEEK and porous trabecular structured titanium (TiLi) interbody cages (n = 4) were inoculated in different bacterial solutions, S.aureus (MSSA, MRSA), S.epidermidis and E.coli. Growth characteristics were analysed. Biofilms and bacteria were visualised using confocal- and electron microscopy.ResultsQuantitative adherence of MSSA, MRSA, S.epidermidis and E.coli to Ti, TiMe and PEEK plates were different, with polished titanium being mainly advantageous over PEEK and TiMe with significantly less counts of colony forming units (CFU) for MRSA after 56 h compared to TiMe and at 72 h compared to PEEK (p = 0.04 and p = 0.005). For MSSA, more adherent bacteria were detected on PEEK than on TiMe at 32 h (p = 0.02). For PEEK and TiLi cages, significant differences were found after 8 and 72 h for S.epidermidis (p = 0.02 and p = 0.008) and after 72 h for MSSA (p = 0.002) with higher bacterial counts on PEEK, whereas E.coli showed more CFU on TiLi than PEEK (p = 0.05). Electron microscopy demonstrated enhanced adhesion in transition areas.ConclusionFor S.epidermidis, MSSA and MRSA PEEK cages showed a higher adherence in terms of CFU count, whereas for E.coli PEEK seemed to be advantageous. Electron microscopic visualisation shows that bacteria did not adhere at the titanium mesh structure, but at the border zones of polished material to rougher parts.

A 16-yr-old male with a genetically undiagnosed neurodevelopmental disorder (NDD) was admitted to our outpatient clinic for skeletal assessment. DXA and HR-pQCT showed a severely reduced BMD and a pronounced reduction of trabecular and cortical bone mass. Lateral vertebral assessment identified multiple previously unrecognized vertebral fractures of the thoracic and lumbar spine. Laboratory tests indicated an activated bone turnover, which was confirmed by an increased number of osteoclasts and osteoblasts in an undecalcified tibia biopsy of the patient. Treatment of the severe osteoporosis was initiated with neridronate. Trio exome sequencing in the patient and healthy parents did not uncover a genetic cause of the disease. Importantly, however, targeted sequencing of the RNU4-2 gene, which encodes the U4 small nuclear RNA (a major component of the splicing machinery), identified a heterozygous causative variant in the patient. This led to the molecular diagnosis of ReNU syndrome. RNU4-2 pathogenic variants underlie a NDD with multisystemic involvement, including skeletal abnormalities. Therefore, this case not only underlines the relevance of osteologic assessment and therapy in individuals with NDDs, but also highlights the necessity of future research efforts to elucidate the bone pathologies in ReNU syndrome.

Piezo proteins are mechanically activated ion channels, which are required for mechanosensing functions in a variety of cell types. While we and others have previously demonstrated that the expression of Piezo1 in osteoblast lineage cells is essential for bone-anabolic processes, there was only suggestive evidence indicating a role of Piezo1 and/or Piezo2 in cartilage. Here we addressed the question if and how chondrocyte expression of the mechanosensitive proteins Piezo1 or Piezo2 controls physiological endochondral ossification and pathological osteoarthritis (OA) development. Mice with chondrocyte-specific inactivation of Piezo1 (Piezo1Col2a1Cre), but not of Piezo2, developed a near absence of trabecular bone below the chondrogenic growth plate postnatally. Moreover, all Piezo1Col2a1Cre animals displayed multiple fractures of rib bones at 7 days of age, which were located close to the growth plates. While skeletal growth was only mildly affected in these mice, OA pathologies were markedly less pronounced compared to littermate controls at 60 weeks of age. Likewise, when OA was induced by anterior cruciate ligament transection, only the chondrocyte inactivation of Piezo1, not of Piezo2, resulted in attenuated articular cartilage degeneration. Importantly, osteophyte formation and maturation were also reduced in Piezo1Col2a1Cre mice. We further observed increased Piezo1 protein abundance in cartilaginous zones of human osteophytes. Finally, we identified Ptgs2 and Ccn2 as potentially relevant Piezo1 downstream genes in chondrocytes. Collectively, our data do not only demonstrate that Piezo1 is a critical regulator of physiological and pathological endochondral ossification processes, but also suggest that Piezo1 antagonists may be established as a novel approach to limit osteophyte formation in OA.

Background/Aim: Intraosseous orbital hemangiomas or vascular malformations (VM) are rare. This report is intended to complement the experience of diagnosing and treating a rare vascular lesion at this site. Special attention is paid to three-dimensional imaging and the morphological distinction between the two entities in this location. Case Report: A 54-year-old female was examined and surgically treated for an exophytic firm mass of the infraorbital, which had become palpable as a hard mass due to growth in size. At first, a bone tumor, for example, an osteoma, was suspected. Intraoperatively, an osseous expansion with distinct fenestrations of the newly grown bone's surface, was detected. The lesion was firmly attaching to the orbital rim. The densely vascularized tumor was well defined to the soft tissues but had grown in continuity from the orbital floor and rim. Vascularized cavities caused the tumor to have a slightly reddish color. The histological examination confirmed the suspicion of the lesion's vascular origin. The lesion's immunohistochemical expression profile approved the final diagnosis of intraosseous VM. Conclusion: The symptoms of intraosseous vascular lesions of the orbit are determined by location and size. Modern imaging techniques facilitate the estimation of tumor-like expansion of lesions. However, the imaging characteristics of intraosseous vascular lesions are very variable. The symptoms of the patient presented herein show that growth phases of a vascular orbital malformation can occur in later stages of life and are initially indistinguishable from a neoplasm. In individual cases, patient care necessitates advanced diagnostic measures to establish the diagnosis and determine surgical therapy.

Background In atlantoaxial instabilities, posterior C1/C2 fusion using lateral mass screws (LMS) or pedicle screws (PS) in a mono- or bicortical position in the atlas is a typical treatment. The bone microstructure and positioning of the screw trajectories appear to be of significant relevance for stability. Purpose The aim of this study was a comparative analysis of the mechanical durability of screw fixation concerning microstructural characteristics of the trajectories of LMS and PS in mono- and bicortical position. Methods Human C1 from geriatric body donors ( n  = 28; 50% female, age 80.8 ± 13.9 years) were collected and characterized based on their bone microstructure. Additionally, the mechanical stability of LMS and PS fixation in mono- and bicortical positioning was tested by mechanical loading. High-resolution quantitative computed tomography was used to analyze the bone microstructure of cylinders corresponding to the trajectories of PS and LMS in mono- and bicortical locations in each C1. After instrumentation with both screw types and types of fixation, the mechanical stability was tested by increased cyclic loading in cranio-caudal direction. Results Trajectories of PS presented with more bone volume and a higher contact length to cortical bone. Simultaneously, a higher number of cycles and a higher maximum force was needed to loosen PS compared to LMS, while the loose by torque at the experiment end was still greater in PS. Differences between mono- and bicortical positioning of PS and LMS have only been observed in the initial stiffness of screws. When comparing microstructural and mechanical properties, the cortical contact length and bone volume in screw trajectories were strongest associated with a high loose and cycle count. Conclusions This study suggests that mono- and bicortical positioning of PS is similarly efficient in creating a stable basis for screw fixation in the atlas. While PS are superior to LMS, the contact with cortical bone is of major relevance for a stable foundation.

Study Design Biomechanical Basic Research. Objectives Type II Fractures of the dens axis (DFTII) are common fractures of the cervical spine in geriatric patients. A surgical approach is the anterior screw fixation (ASF). However, a disadvantage is the high post-operative rate of non-union. This study aimed to develop and biomechanically test an osteosynthesis plate (OSP) for the anterior treatment of DFTII in comparison to ASF. Methods A novel OSP was developed and manufactured. The OSP was biomechanically tested in comparison to ASF in synthetic bone models and geriatric human cadaveric bone. An analysis of the bone microstructure of the human C2 vertebrae was performed utilizing high-resolution quantitative computed tomography to exclude differences in bone quality among the experimental groups. Biomechanical testing was performed by cyclic loading of compression and tensile forces until failure. Results In the comparative biomechanical analysis of ASF and OSP in synthetic bone, significant differences were observed regarding the load to failure, favoring the OSP (P = 0.040). The comparative biomechanical analysis of ASF and OSP in the cadaveric specimens also revealed a significantly lower load to failure of the ASF (P = 0.046). The experimental groups did not show significant differences regarding age, sex or bone microstructure. Conclusions The current study demonstrated that the OSP is biomechanically superior to the ASF, indicating higher stability. This study provides the basis for an alternative anterior treatment option for DFTII.

The recent identification of homozygous WNT1 mutations in individuals with osteogenesis imperfecta type XV (OI-XV) has suggested that WNT1 is a key ligand promoting the differentiation and function of bone-forming osteoblasts. Although such an influence was supported by subsequent studies, a mouse model of OI-XV remained to be established. Therefore, we introduced a previously identified disease-causing mutation (G177C) into the murine Wnt1 gene. Homozygous Wnt1G177C/G177C mice were viable and did not display defects in brain development, but the majority of 24-week-old Wnt1G177C/G177C mice had skeletal fractures. This increased bone fragility was not fully explained by reduced bone mass but also by impaired bone matrix quality. Importantly, the homozygous presence of the G177C mutation did not interfere with the osteoanabolic influence of either parathyroid hormone injection or activating mutation of LRP5, the latter mimicking the effect of sclerostin neutralization. Finally, transcriptomic analyses revealed that short-term administration of WNT1 to osteogenic cells induced not only the expression of canonical WNT signaling targets but also the expression of genes encoding extracellular matrix modifiers. Taken together, our data demonstrate that regulating bone matrix quality is a primary function of WNT1. They further suggest that individuals with WNT1 mutations should profit from existing osteoanabolic therapies.

Poor bone quality is a critical factor associated with an increased risk of complications after total hip arthroplasty (THA). However, no consistent recommendations have yet been established for assessing indicators of bone quality preoperatively. Thus, it remains unclear which preoperatively available and readily accessible parameters are most closely associated with femoral bone quality. Here, we obtained femoral neck specimens from 50 patients undergoing THA. Preoperative Dual-energy X-ray absorptiometry (DXA) scans, pelvic radiographs, and laboratory parameters were analyzed. In the obtained specimens, bone microstructure was assessed using micro-CT and histomorphometry. Additionally, matrix mineralization and osteocyte lacunar morphology were evaluated using quantitative backscattered electron imaging. Our analysis revealed that DXA-derived T-scores correlated with trabecular microstructure. Furthermore, radiographic indices and body mass index correlated differentially with aspects of bone quality in women and men. Contrary to previous observations, no correlation was found between serum vitamin D levels and osteoid indices, nor between clinical parameters and matrix mineralization. Age was strongly associated with the number of mineralized osteocyte lacunae, a factor that appeared to be independent of sex. Taken together, our study demonstrates that no single preoperatively available parameter exhibits a strong and consistent association with femoral bone quality. However, DXA remains a reliable preoperative measure for determining the trabecular microstructure of the femoral neck. In clinical practice, surgeons should adopt an individualized approach to preoperative assessments by considering age, sex, BMI, and radiographic indices to enhance their insight into femoral bone quality, particularly when DXA is unavailable.