Recommendations for High-resolution Peripheral Quantitative Computed Tomography Assessment of Bone Density, Microarchitecture, and Strength in Pediatric Populations.

Purpose Of Review: The purpose of this review is to summarize current approaches and provide recommendations for imaging bone in pediatric populations using high-resolution peripheral quantitative computed tomography (HR-pQCT).

Recent Findings: Imaging the growing skeleton is challenging and HR-pQCT protocols are not standardized across centers. Adopting a single-imaging protocol for all studies is unrealistic; thus, we present three established protocols for HR-pQCT imaging in children and adolescents and share advantages and disadvantages of each.

Breed and loading history influence in vivo skeletal strain patterns in pre-pubertal female chickens.

The influence of loading history on in vivo strains within a given specie remains poorly understood, and although in vivo strains have been measured at the hindlimb bones of various species, strains engendered during modes of activity other than locomotion are lacking, particularly in non-human species. For commercial egg-laying chickens specifically, there is an interest in understanding their bones' mechanical behaviour, particularly during youth, to develop early interventions to prevent the high incidence of osteoporosis in this population. We measured in vivo mechanical strains at the tibiotarsus midshaft during steady activities (ground, uphill, downhill locomotion) and non-steady activities (perching, jumping, aerial transition landing) in 48 pre-pubescent female (egg-laying) chickens from two breeds that were reared in three different housing systems, allowing varying amounts and types of physical activity.

Pectus Excavatum: Consensus and Controversies in Clinical Practice.

Background: Pectus excavatum is the most common congenital anterior chest wall deformity. Currently, a wide variety of diagnostic protocols and criteria for corrective surgery are being used. Their use is predominantly based on local preferences and experience.

Standardized growth charts for children with osteogenesis imperfecta.

Background: Osteogenesis imperfecta (OI) is associated with short stature, which is mild, severe and moderate in OI types I, III and IV, respectively. Standardized OI type- and sex-specific growth charts across all pediatric ages do not exist.

Methods: We assessed 573 individuals with OI (type I, III or IV), each with at least one height measurement between ages 3 months and 20 years (total 6523 observations).

Bi-allelic mutation in SEC16B alters collagen trafficking and increases ER stress.

Osteogenesis imperfecta (OI) is a genetically and clinically heterogeneous disorder characterized by bone fragility and reduced bone mass generally caused by defects in type I collagen structure or defects in proteins interacting with collagen processing. We identified a homozygous missense mutation in SEC16B in a child with vertebral fractures, leg bowing, short stature, muscular hypotonia, and bone densitometric and histomorphometric features in keeping with OI with distinct ultrastructural features. In line with the putative function of SEC16B as a regulator of trafficking between the ER and the Golgi complex, we showed that patient fibroblasts accumulated type I procollagen in the ER and exhibited a general trafficking defect at the level of the ER.

USP53 Regulates Bone Homeostasis by Controlling Rankl Expression in Osteoblasts and Bone Marrow Adipocytes.

In the skeleton, osteoblasts and osteoclasts synchronize their activities to maintain bone homeostasis and integrity. Investigating the molecular mechanisms governing bone remodeling is critical and helps understand the underlying biology of bone disorders. Initially, we have identified the ubiquitin-specific peptidase gene (Usp53) as a target of the parathyroid hormone in osteoblasts and a regulator of mesenchymal stem cell differentiation.

Equation predicting tibial-tuberosity to trochlear-groove distance following supratubercle osteotomy: Radiographic proof of concept.

Background: Supratubercle tibial rotational osteotomies are useful in patellar stabilizing procedures with high tibial-tuberosity to trochlear-groove distance caused by excessive external tibial torsion. An investigation determined one degree of internal tibial rotation results in 0.68 mm reduction of tibial-tuberosity to trochlear-groove distance, but did not account for anatomical variability.

Effect of the accordion technique on bone regeneration during distraction osteogenesis: A computational study.

Background And Objective: Distraction osteogenesis (DO), a bone lengthening technique, is widely employed to treat congenital and acquired limb length discrepancies and large segmental bone defects. However, a major issue of DO is the prolonged consolidation phase (10-36 months) during which patients must wear a cumbersome external fixator. Attempts have been made to accelerate the healing process of DO by an alternating distraction and compression mode (so-called "accordion" technique or AT).

Patellofemoral Instability Part I: Evaluation and Nonsurgical Treatment.

Patellofemoral instability (PFI) is a prevalent cause of knee pain and disability. It affects mostly young females with an incidence reported as high as 1 in 1,000. Risk factors for instability include trochlear dysplasia, patella alta, increased tibial tubercle-to-trochlear groove distance, abnormal patella lateral tilt, and coronal and torsional malalignment.

Craniofacial and dental phenotype of two girls with osteogenesis imperfecta due to mutations in CRTAP.

Mutations in CRTAP lead to an extremely rare form of recessive osteogenesis imperfecta (OI). CRTAP deficient mice have a brachycephalic skull, fusion of facial bones, midface retrusion and class III dental malocclusion, but in humans, the craniofacial and dental phenotype has not been reported in detail. Here, we describe craniofacial and dental findings in two 11-year-old girls with biallelic CRTAP mutations.

Vitamin D and Diseases of Mineral Homeostasis: A R396W Humanized Preclinical Model of Infantile Hypercalcemia Type 1.

Infantile hypercalcemia type 1 (HCINF1), previously known as idiopathic infantile hypercalcemia, is caused by mutations in the 25-hydroxyvitamin D 24-hydroxylase gene, . The R396W loss-of-function mutation in is the second most frequent mutated allele observed in affected HCINF1 patients. We have introduced the site-specific R396W mutation within the murine gene in knock-in mice to generate a humanized model of HCINF1.

mutation in LDS3 causes bone fragility by impairing the TGF-β pathway and enhancing osteoclastogenesis.

Loss-of-function mutations in cause Loeys-Dietz syndrome type 3 (LDS3), a rare autosomal-dominant connective tissue disorder characterized by vascular pathology and skeletal abnormalities. Dysregulation of TGF-β/SMAD signaling is associated with abnormal skeletal features and bone fragility. To date, histomorphometric and ultrastructural characteristics of bone with mutations have not been reported in humans and the exact mechanism by which mutations cause the LDS3 phenotype is poorly understood.

Research Note: Effect of light intensity of calcium homeostasis in pullets.

The impact of varying light intensities on layer pullets is not yet well understood. Behaviorally, brighter illumination may increase pullet activity levels by allowing better navigation in the complexity of non-cage systems. In addition, light intensity was previously demonstrated to affect the levels of calcium and phosphate regulating hormones in mice.

Male Marfan mice are predisposed to high-fat diet-induced obesity, diabetes, and fatty liver.

Gene mutations in the extracellular matrix protein fibrillin-1 cause connective tissue disorders including Marfan syndrome (MFS) with clinical symptoms in the cardiovascular, skeletal, and ocular systems. Patients with MFS also exhibit alterations in adipose tissues, which in some individuals leads to lipodystrophy, whereas in others to obesity. We have recently demonstrated that fibrillin-1 regulates adipose tissue homeostasis.

Platelets and osteoblasts: secretome connections.

Megakaryocyte hyperplasia associated with myeloproliferative neoplasms commonly leads to abnormal bone tissue deposition in the bone marrow, known as osteosclerosis. In this study, we aimed to synthesize the known proteomics literature describing factors released by megakaryocytes and platelets and to examine if any of the secreted factors have a known ability to stimulate the bone-forming cells, osteoblasts. Using a systematic search of Medline, we identified 77 articles reporting on factors secreted by platelets and megakaryocytes.

Pubertal growth in osteogenesis imperfecta caused by pathogenic variants in COL1A1/COL1A2.

Purpose: Short stature is common in osteogenesis imperfecta (OI) and is usually severe in OI types III and IV. The characteristics of pubertal growth in OI have not been studied in detail.

Methods: We assessed 82 individuals with OI caused by pathogenic variants in COL1A1 or COL1A2 who had annual height data between 6 and 16 years of age at a minimum.

Fibrillin-1-regulated miR-122 has a critical role in thoracic aortic aneurysm formation.

Thoracic aortic aneurysms (TAA) in Marfan syndrome, caused by fibrillin-1 mutations, are characterized by elevated cytokines and fragmentated elastic laminae in the aortic wall. This study explored whether and how specific fibrillin-1-regulated miRNAs mediate inflammatory cytokine expression and elastic laminae degradation in TAA. miRNA expression profiling at early and late TAA stages using a severe Marfan mouse model (Fbn1) revealed a spectrum of differentially regulated miRNAs.

In vivo microCT-based time-lapse morphometry reveals anatomical site-specific differences in bone (re)modeling serving as baseline parameters to detect early pathological events.

The bone structure is very dynamic and continuously adapts its geometry to external stimuli by modeling and remodeling the mineralized tissue. In vivo microCT-based time-lapse morphometry is a powerful tool to study the temporal and spatial dynamics of bone (re)modeling. Here an advancement in the methodology to detect and quantify site-specific differences in bone (re)modeling of 12-week-old BALB/c nude mice is presented.

Bone strength and composition in spacefaring rodents: systematic review and meta-analysis.

Studying the effects of space travel on bone of experimental animals provides unique advantages, including the ability to perform post-mortem analysis and mechanical testing. To synthesize the available data to assess how much and how consistently bone strength and composition parameters are affected by spaceflight, we systematically identified studies reporting bone health in spacefaring animals from Medline, Embase, Web of Science, BIOSIS, and NASA Technical reports. Previously, we reported the effect of spaceflight on bone architecture and turnover in rodents and primates.

Dominant osteogenesis imperfecta with low bone turnover caused by a heterozygous SP7 variant.

Mutations in SP7 (encoding osterix) have been identified as a rare cause of recessive osteogenesis imperfecta ('OI type XII') and in one case of dominant juvenile Paget's disease. We present the first description of young adult siblings with OI due to a unique heterozygous mutation in SP7. The phenotype was characterized by fragility fractures (primarily of the long bone diaphyses), poor healing, scoliosis, and dental malocclusion.

Craniofacial Bones and Teeth in Spacefarers: Systematic Review and Meta-analysis.

Introduction: Estimating the risk of dental problems in long-duration space missions to the Moon and Mars is critical for avoiding dental emergencies in an environment that does not support proper treatment. Previous risk estimates were constructed based on the experience in short-duration space missions and isolated environments on Earth. However, previous estimates did not account for potential changes in dental structures due to space travel, even though bone loss is a known problem for long-duration spaceflights.

3D Image Registration Marginally Improves the Precision of HR-pQCT Measurements Compared to Cross-Sectional-Area Registration in Adults With Osteogenesis Imperfecta.

Repositioning error in longitudinal high-resolution peripheral-quantitative computed tomography (HR-pQCT) imaging can lead to different bone volumes being assessed over time. To identify the same bone volumes at each time point, image registration is used. While cross-sectional area image registration corrects axial misalignment, 3D registration additionally corrects rotations.