The Development of a Magnesium-Releasing and Long-Term Mechanically Stable Calcium Phosphate Bone Cement Possessing Osteogenic and Immunomodulation Effects for Promoting Bone Fracture Regeneration

Bone grafts are commonly used for the treatment of critical sized bone defects. Since the supply of autologous bone is insufficient, allogeneic bone grafts have been used most of the time. However, the poor osteogenic property of allogeneic bone grafts after pretreatment results in delayed union, non-union, or even occasional deformity. Calcium phosphate cement (CPC) is one of the most promising bone filling materials due to its good biocompatibility and similar chemical components as natural bone. However, clinical applications of CPC were hampered by limited osteogenic effects, undesired immune response which results in resorption, and poor mechanical stability in vivo. Magnesium (Mg) has been proven to trigger bone regeneration through modulating cell behaviors of mesenchymal stem cells and macrophages significantly. Unfortunately, the degradation raters of pure Mg and Mg oxide are extremely fast, resulting in early collapse of Mg contained CPC. In this study, we developed a novel magnesium contained calcium phosphate bone cement (Mg-CPC), possessing long-term mechanical stability and osteogenic effects through sustained release of Mg. Furthermore, in vitro studies showed that Mg-CPC had no cytotoxic effects on hBMMSCs and macrophage RAW 264.7, and could enhance the osteogenic differentiation as determined by alkaline phosphate (ALP) activity and calcium nodule staining, as well as suppress the inflammatory as determined by expression of anti-inflammatory cytokine IL-1RA. We also found that Mg-CPC promoted new bone formation and bone maturation in vivo. These results suggest that Mg-CPC should be a good substitute material for bone grafts in clinical use.

The Healing of Bone Defects by Cell-Free and Stem Cell-Seeded 3D Printed PLA Tissue Engineered Scaffolds

One of the main issues in bone tissue engineering is to realize the response of the host to the engineered scaffolds. In this paper, the in-vivo healing of critical-sized bony defects by cell-free and stem cell-seeded 3D printed PLA scaffolds was studied in rat calvaria bone. First, the scaffolds were 3D printed based on a designed computer model and half of them were seeded by with bone marrow-derived mesenchymal stem cells (BMSCs). The SEM images of the surfaces of PLA and PLA+Cell scaffolds were taken for morphological analysis. All the scaffolds were implanted in the defect sites of rat calvaria bones and histological analysis was conducted after 8 and 12 weeks. The results showed that both cell-free and stem cell-seeded scaffolds exhibited superb healing compared with the empty defect controls. The histological observation revealed the formation of both new bone and connective tissues in the healing site after 8 and 12 weeks, postoperatively. The bone cells including osteoblasts and osteocytes with lacuna were also observed. The higher filled area and the higher bone formation and bone maturation were observed after 12 weeks and in particular for PLA+Cell scaffolds. Furthermore, the systemic toxicity evaluation of the scaffolds using ALT and AST tests reject any toxicity for both cell-free and stem cell-seeded scaffolds. It can be concluded that the 3D printed PLA scaffold with BMSCs seeding has well osteogenic potential to be used for bone defect healing.

Estimating Cervical Vertebral Maturation with a Lateral Cephalogram Using the Convolutional Neural Network

Recently, the estimation of bone maturation using deep learning has been actively conducted. However, many studies have considered hand–wrist radiographs, while a few studies have focused on estimating cervical vertebral maturation (CVM) using lateral cephalograms. This study proposes the use of deep learning models for estimating CVM from lateral cephalograms. As the second, third, and fourth cervical vertebral regions (denoted as C2, C3, and C4, respectively) are considerably smaller than the whole image, we propose a stepwise segmentation-based model that focuses on the C2–C4 regions. We propose three convolutional neural network-based classification models: a one-step model with only CVM classification, a two-step model with region of interest (ROI) detection and CVM classification, and a three-step model with ROI detection, cervical segmentation, and CVM classification. Our dataset contains 600 lateral cephalogram images, comprising six classes with 100 images each. The three-step segmentation-based model produced the best accuracy (62.5%) compared to the models that were not segmentation-based.

Concordance of SMI and CVMS bone maturation indices in pubertal growth stages – cross-sectional study

In order to verify the concordance of the bone development indices (SMI) estimated on the hand and fist radiograph by the method of Fishman (1982) and the indices of development of the cervical vertebrae (CVMS), estimated on the profile teleradiography by the method of Baccetti (2002), was conducted a cross-sectional study on a group of 150 subjects (89 girls and 61 boys), aged 8-18 years. Based on the existing data in the literature and taking into account the average ages at which the SMI and CVMS stages were reached in the research group, a hypothesis of correspondence between SMI and CVMS stages in the pubertal stages was issued and this hypothesis was statistically verified using the coefficient Cohen k. The obtained results (k = 0.82 for the girls 'group and k = 0.67 for the boys' group) confirm the concordance of the SMI and CVMS indices within the researched group and validate the correspondence hypothesis issued.

METABOLIC AND ORTHOPEDIC ASPECT OF X-LINKED VITAMIN D-RESISTANT HYPOPHOSPHATEMIC RICKETS

INTRODUCTION: - The X-linked vitamin D-resistant hypophosphatemic rickets (VDXLR) is a metabolic disorder. Medication treatment consists of oral phosphate substitution and supplementation of active vitamin D compounds. Our study aimed to review our patients with VDXLR, focusing on those undergoing surgery, mainly lengthening procedures. The main parameters of interest were growth, height, the axis of the lower limbs, pain, and degenerative arthropathy. METHODS: - Twelve patients with VDXLR were followed at our institution. Eight patients underwent surgical correction, and three of them in combination with bone lengthening. The corrections were executed at the end of growth in the patients. Clinical end points were height, leg axis, and pain. RESULTS: - Single bilateral surgical correction was performed in six patients; one patient had three and ve corrections. Bone lengthening was performed in three patients. At the last follow-up, the height of seven operated patients was within normal range. In addition, the leg axis was normalized in six patients with mild genua vara in two. Bone healing was excellent, and no surgical complications. There was no one radiological evidence of degenerative arthropathy. CONCLUSIONS: - In case of bone deformity, surgery can safely be performed, independent of age or bone maturation. All patients were happy with the outcomes of axial corrective surgery and bone lengthening, and in the majority. Only one corrective intervention was needed.

Relationship between obesity and musculoskeletal disorders: A scope review protocol

Obesity is considered a public health problem and the review of the scientific literature allows the observation of several changes in the musculoskeletal system associated with this disease. The objective of this study is to describe the relationship between these changes in obese children and adults. This article is a scope review protocol, a study methodology based on the structure described by Arksey and O'Malley. The study protocol followed the recommendations from the Preferred Reporting Items for Systematic reviews and Meta-Analyzes extension for Scoping Reviews (PRISMA-ScR) Checklis. It will be conducted in five stages: a) elaboration of the research question; b) identification of relevant studies; c) selection of studies; d) data extraction; e) summary of the results. The study aims to correlate musculoskeletal disorders in obesity, in different stages of bone maturation, which are less studied, in order to provide scientific evidence to health care professionals involved in the multidisciplinary treatment of this chronic disease.

Central Precocious Puberty in Girls: Diagnosis, Management and Outcome

Puberty is a normal physiological process of during which children develop secondary sex characteristics, experience growth acceleration, and achieve bone maturation and reproductive competence. The onset of puberty is initiated by the activation of the hypothalamic-pituitary-gonadal (HPG) axis. Precocious puberty is defined as the appearance of secondary sex characteristic at an age younger than 8 years in girls and 9 years in boys, or the beginning of menstruation before 9 years in girls. The most common etiology of central precocious puberty (CPP) is idiopathic (>90.0% in girls and 25.0-60.0% in boys), in which at present the etiologies of idiopathic CPP in some patients can be identified to be from a mutation of KISS1 or MKRN3 genes. The standard treatment for CPP is a gonadotropin-releasing hormone analog (GnRHa). The aims of treatment are to halt and regress the pubertal status of the patient to the prepubertal state that is appropriate for their age, prevent early onset of menses and attenuate the loss of height potential consequence upon advanced skeletal maturation. A study of long-term follow-ups of former CPP women at the age of mid-20s to 50 years found that most of the participants had regular menstrual cycles. The marital status and the pregnancy rate were the same as in controlled group and were not different between the GnRHa-treated and untreated CPP women.

Diagnostic re-evaluation and predictors of congenital hypothyroidism with eutopic thyroid gland in Jiangxi, China

Objectives An increase in the incidence of congenital hypothyroidism (CH) with eutopic gland has been reported worldwide due to neonatal screening programs. In this study, we aimed to determine the prevalence of transient CH (TCH) and to investigate predictive factors that could distinguish between permanent and transient CH in patients with eutopic thyroid glands. Methods We retrospectively reviewed 508 children treated for CH with eutopic thyroid glands between June 1998 and June 2020 in Jiangxi Newborn Screening Center. All patients were treated with levothyroxine and underwent Diagnostic re-evaluation after 2–3 years of age. Patients were classified as having TCH or permanent CH (PCH) during follow-up. Results Of the 508 patients initially treated for CH with a normally located gland, 335 patients (65.9%) were classified in the TCH group and 173 (34.1%) in the PCH group based on the defined criteria. Multivariate analysis revealed that TCH was associated with a lower levothyroxine dose at 24 months of age (p<0.001) and a lower likelihood of having a first-degree family history of CH (p=0.026) than PCH. Gender, prematurity, low birth weight, initial CH severity such as serum TSH and FT4 levels, or bone maturation delay at diagnosis had no effect. Receiver operating characteristics curve analysis showed that a cutoff of 2.3 μg/kg/day for levothyroxine dose requirement at 24 months of age had a sensitivity of 71% and a specificity of 70% for predicting transient CH, with values below this threshold considered predictive of transient CH. Conclusions TCH presents a significant portion of patients with CH. The levothyroxine dose requirement at 24 months of age has a predictive role in differentiating TCH from PCH in CH patients with eutopic thyroid glands.