The Ins and Outs of Neonatal Orthopedic Disorders: Back to Basics.

Calcium supplementation during pregnancy and lactation: Effects on the mother and the fetus

Bone Research Society Abstracts

Genistein, a major phytoestrogen of soy, is considered a potential drug for prevention and treatment of postmenopausal osteoporosis. The aim of the present study was to compare the effects of genistein, estradiol and raloxifene on the skeletal system in vivo and in vitro. Genistein (5 mg/kg), estradiol (0.1 mg/kg) or raloxifene hydrochloride (5 mg/kg) were administered daily by a stomach tube to mature ovariectomized Wistar rats for 4 weeks. Bone mass, mineral and calcium content, macrometric parameters and mechanical properties were examined. Also the effects of genistein, estradiol and raloxifene (10(-9)-10(-7) M) on the formation of osteoclasts from neonatal mouse bone marrow cells and the activity of osteoblasts isolated from neonatal mouse calvariae were compared. In vivo, estrogen deficiency resulted in the impairment of bone mineralization and bone mechanical properties. Raloxifene but not estradiol or genistein improved bone mineralization. Estradiol fully normalized the bone mechanical properties, whereas genistein augmented the deleterious effect of estrogen-deficiency on bone strength. In vitro, genistein, estradiol and raloxifene inhibited osteoclast formation from mouse bone marrow cells, decreasing the ratio of RANKL mRNA to osteoprotegerin mRNA expression in osteoblasts. Genistein, but not estradiol or raloxifene, decreased the ratio of alkaline phosphatase mRNA to ectonucleotide pyrophosphatase phosphodiesterase 1 mRNA expression in osteoblasts. This difference may explain the lack of genistein effect on bone mineralization observed in ovariectomized rats in the in vivo study. Concluding, our experiments demonstrated profound differences between the activities of genistein, estradiol and raloxifene towards the osseous tissue in experimental conditions.

To review the various mechanisms of glucocorticoid action and the ability of these agents to induce osteoporosis and growth deficits. A review of the scientific literature was conducted on the basis of a MEDLINE search using the keywords and descriptors "glucocorticoids," "bone mineralization," "growth," and "side effects" and limited to articles published in the last decade. The references cited by these articles were used to identify relevant older publications, with an emphasis on landmark studies essential to an understanding of the topic. Emphasis was placed on the actions of glucocorticoids on the hormones and cytokines that modulate linear growth. The end effects of glucocorticoids on the skeletal system are the result of systemic effects on bone metabolism and of direct actions on bone cells, which alter bone cell counts and predispose to bone loss. The mechanisms underlying catch-up growth and bone mass recovery after discontinuation of glucocorticoid treatment are discussed, followed by a review of diagnostic methods available for assessment of bone metabolism and mineralization and of measures for prevention and management of glucocorticoid-induced bone changes. Patient monitoring on a case-by-case basis plays an essential role in detection and, potentially, reversal of the damage associated with chronic glucocorticoid therapy.

Interpretation of analysis of variance models using principal component analysis to assess the effect of a maternal anticancer treatment on the mineralization of rat bones

Bone mass and bone metabolism in pediatric gastrointestinal disorders.

The aim of this paper is to show one of the most important intervention ways to improve the school climate currently: the Conflict Resolution Education. First of all, we show the contents to teach resolving conflicts correctly. Conflict Resolution Education supposes to teach children negotiating, mediating or reaching collective consensus. About that, we should teach process steps and necessary attitudes, principles and skills. Secondly, we show the principal ways to integrate these contents in educative curricula. They can be inserted in schools by mean of four

Objective To analyze high alumina deformation Micro-CT findings of bone in patients with skeletal fluorosis in Shuicheng Guizhou Province.Methods Bone deformation children,youth and middle-aged patients with fluorosis in Goumi and Zhichang Townships Shuicheng County,coal-burning pollution endemic fluorosis areas,were selected as case group,and non-bone deformation children,youth,and children from non-fluorosis endemic areas as controls.Tibia and the anterior superior iliac spine tissue were obtained through orthopedic surgery and etiology examination,and resin embedded without decalcification.Resin-embedded bone tissue was scanned using micro-CT; relevant parameters were analyzed with ABA special bone analysis software INVEON Research Workplace and three dimensional reconstruction processing software Micview.Results ①The anterior superior iliac spine cancellous bone:compared between bone deformation children and bone non-deformation children in the diseased areas,there was an increasing tendency of the following items:relative volume of trabecular bone(0.337％ vs 0.229％),absolute thickness (μm:139 vs 133),quantities within a unit length (number/mm:2.44 vs 1.72),density woven degree of trabecular bone(number/mm:2.22 vs 1.54) and bone mineral density(mg/cm3:1 033 vs 918),while relative bone area of trabecular bone(mm2/mm3:14.5 vs 15.1) and space pitch (μm:0.274 vs 0.567) declined.Compared between bone deformation youth and bone non-deformation youth in the diseased areas,relative volume of trabecular bone was lower(0.217％ vs 0.437％),relative area increased (mm2/mm3:16.9 vs 11.6),absolute thickness reduced(μm:118 vs 172),trabecular number reduced (number/mm:1.83 vs 2.54),and space pitch increased (μm:0.427 vs 0.222),but density woven degree of trabecular bone increased (number/mm:4.61 vs 1.54),bone mineral density decreased(mg/cm3:977 vs 1 108),osteopenia,osteoporosis,bone mineral decreased,and an increase in the number of trabeculae crossing number.② Tibia bone tissue:compared between bone deformation children and bone non-deformation children in the diseased areas,relative volume of tibia trabecular bone increased(0.435％ vs 0.206％),relative volume of trabecular bone (mm2/mm3:12.3vs 12.4),and thickness (μm:188 vs 161) not changed obviously,trabecular number increased (number/mm:2.43 vs 1.28),space pitch reduced(μm:0.238 vs 0.621),density woven degree of trabecular bone decreased(number/mm:2.40 vs 3.48),bone mineral density increased(mg/cm3:1 047 vs 952),in general presented trabecular thickening,increased number and increased bone mineral.Compared between middle-aged patients with fluorosis in the diseased areas and children in non-fluorosis endemic areas,relative volume of trabecular bone (0.346％ vs 0.206％) and area (mm2/mm3:13.8 vs 12.4) increased,thickness of the trabecular bone reduced (μm:144 vs 161),trabecular number increased (number/mm:1.98 vs 1.28),space pitch decreased (μm:0.318 vs 0.621),and density woven degree of trabecular bone decreased (number/mm:2.60 vs 3.48).Conclusions The results of trabecular bone microstructure and bone mineral density have showed that the combined effects of aluminum and fluorine on human bone tissue at different developmental stages are different.High aluminum and fluorine load before the sexual development of children for trabecular bone thick dense,shows an increasing in bone mass and bone mineral deposition of bone sclerosis image.Bone deformation youth shows osteopenia osteoporosis and bone mineral deposition is reduced.Bone volume is slightly increased,the number of trabecular bone is increasing,trabecular structure is fine in middle-aged patients with skeletal fluorosis. Key words: Aluminum ; Fluoride poisoning; Osteomalacia; Sclerotin

Sickle cell disease (SCD) is the best known haemoglobinopathy, caused by a mutation substituting valina for glutamic acid at position 6 of the beta-globin chain of adult hemoglobin A, resulting in hemoglobin S (HbS). The homozygous HbS disease (HbSS), an autosomal recessive disorder, is the most common form and the Mediterranean area, along with sub-Saharian African and India, have the highest prevalence (1%-15%). In particular, Sicily with a prevalence of 2%-5%, is among the most interested regions. However, migratory flows have led to a wider diffusion of the disease no longer confined to endemic areas. In Europe, the yearly estimate of affected births are 1,300 but more than 90% of children with SCD survive into adulthood thanks to screening programs and early available care; however, their lifespan remains shortened by two or three decades compared to general population. In Greece, the number of affected births surpassing 100,000 yearly and the total number of newborns carrying two deleterious genes, if no prevention measures are taken, is estimated to be about 120-130/year. Diagnosis of SCD is based on analysis of haemoglobin through protein electrophoresis or chromatography, that are cheap and widely available techniques, even if haemoglobin mass spectrometry and DNA analysis are techniques with high-throughput testing. Prenatal diagnosis is used in many European countries, so the number of affected newborns has significantly decreased during the last 3 years. Over the course of SCD, sickling process may cause acute and chronic abdominal pain due to vaso-occlusive crisis, bone pain often in long bones due to bone marrow infarction, chronic hemolytic anemia, splenic sequestration with rapid enlargement of the spleen, delayed sexual maturation and cholelithiasis, with important inter-indivuidual variability. Sickle hepatopathy reflects liver sickling process within hepatic sinusoids and includes gallstone disease, hepatic sequestration, hepatic sideroris, acute sickle cell hepatic crises (ASHC) and sickle cell intrahepatic cholestasis (SCIC). Clinically, it appears with fever, right upper quadrant pain, jaundice and increased serum liver function tests. These patients are repeatedly esposed to trasfused red cells that contributes to iron overload and may contribute to hepatic haemosiderosis. Increased bone turnover and resorption by osteoclasts and by marrow expansion due to activation of hematopoiesis. The hematopoietic system may expand physiologically. Computed tomography (CT) is an easily reproducible imaging method that allows the morphologic whole-body evaluation although with a high dose of radiation exposure and possible side effects from intravenous contrast media. Magnetic resonance cholangiopancreatography (MRCP) is a noninvasive technique without radiation chosen to image cholangiopathy and may be followed by the execution of endoscopic retrograde cholangiopancreatography (ERCP) in case of gallstone disease. Otherwise it can be helpful in identifying extramedullary hematopoiesis sites. Dual-energy X-rays absorptiometry (DEXA) is performed to evaluate deficit of bone mineral density (BMD), in which reduction of osteoblastic activity, high risk for necrosis may induce to fragility fractures. We recently had the experience of a typical case of a 56 years old Albanian woman with SCD, with jaundice after a long history of recurrent vaso-occlusive crisis. She was submitted to splenectomy and cholecystectomy 5 years before and since then she was treated with hydroxyurea. Hemocromatosis was excluded by genetic analysis. Hepatic biopsy (Pearl's stain) showed sinusoidal dilatation and diffuse iron accumulation in hepatocytes and Kupffer cells. Endo-hepatic jaundice was observed in MRCP images. It was interesting that DEXA examination was within normal range in both right proximal femur. This may probably be due to the presence of sclerotic lesions in the vertebrae, as was seen in the CT images. Technetium-99m-methylen bisphosphonate (99mTc-MDP) skeletal scintigraphy is a higly sensitive whole-body diagnostic nuclear medicine technique able to evaluate early bone metabolic changes. Multimodality SPET/CT allows to correlate scintigraphic findings with anatomical images with higher sensitivity and specificity. The higher uptake of 99mTc-MDP in SCD patients is due to the activation of hematopoetic system and relies on the osteoblastic response to bone resorption as in our patient. The 99mTc-MDP scan may be better than fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) to show sclerotic lesions. Technetium-99m nanocolloids bone marrow scintigraphy (BMS) provides information about the assessment of the reticulum-endothelial system (RES), the whole-body distribution of functional red bone marrow and the presence and the extent of extramedullary hematopoiesis, especially in liver, spleen and bone marrow. Fluorine-18-FDG PET/CT completes the whole-body assessment with an integrated multimodal approach with high spatial resolution that evaluates the metabolic activity and the standardized uptake value (SUV) in SCD patients. Modern genetic diagnosis and gene treatment give promise for having fewer cases of SCD in the future.

The mechanisms by which mineralized tissues such as bone acquire and regulate their mineral component are complex. The process of mineralization can be divided into the establishment of a primed, mineralizable matrix in which de novo mineral nucleation can occur, followed by the growth, expansion, and maturation of crystals. Perturbations in any of these events can result in bone disease and fragility. Elucidating the cellular and molecular mechanisms has been difficult because biomineralization is a combination of a physico-chemical process and a biological one. For example, phosphate participates directly in the formation of the hydroxyapatite crystals but recent studies have shown that phosphate can also directly regulate gene expression. This chapter summarizes current opinion within the field on key issues related to mineralization, such as whether mineralization is an active (cell-mediated) or a passive (physico-chemical) process and the role of cell-derived organelles/vesicles in mineralization. The molecular mediators and regulators of mineralization are reviewed and the question of whether there are unique mechanisms of mineralization in different types of bone tissue is addressed. Even though bone mineral density is currently the standard for predicting bone fragility, it is important to not only understand the inorganic component of bone, but also the organic component, as individuals with similar bone densities can have different susceptibility to fracture. These less clear properties of the skeleton that contribute to bone strength remain the focus of much investigation. THE CELLS RESPONSIBLE FOR BONE FORMATION AND MINERALIZATION Cells in the osteoblast/osteocyte lineage are responsible for bone formation...

Long-term glucocorticoid administration to growing rats induces osteopenia and alterations in the biomechanical behavior of the bone. This study was performed to estimate the effects of dexamethasone (DTX), a synthetic steroid with predominant glucocorticoid activity, on the biomechanical properties of the mandible of rats during the growth phase, as assessed by bending test and peripheral quantitative computed tomographic (pQCT) analysis. The data obtained by the two methods will provide more precise information when analyzed together than separately. Female rats aged 23 d (n=7) received 500μg.kg-1 per day of DXT for 4 weeks. At the end of the treatment period, their body weight and body length were 51.3% and 20.6% lower, respectively, than controls. Hemimandible weight and area (an index of mandibular size) were 27.3% and 9.7% lower, respectively. The right hemimandible of each animal was subjected to a mechanical 3-point bending test. Significant weakening of the bone, as shown by a correlative impairment of strength and stiffness, was observed in experimental rats. Bone density and cross-sectional area were measured by pQCT. Cross-sectional, cortical and trabecular areas were reduced by 20% to 30% in the DTX group, as were other cortical parameters, including the bone density, mineral content and cross-sectional moment of inertia. The "bone strength index" (BSI, the product of the pQCT-assessed xCSMI and vCtBMD) was 56% lower in treated rats, which compares well with the 54% and 52% reduction observed in mandibular strength and stiffness determined through the bending test. Data suggest that the corticosteroid exerts a combined, negative action on bone geometry (mass and architecture) and volumetric bone mineral density of cortical bone, which would express independent effects on both cellular (material quality) and tissue (cross-sectional design) levels of biological organization of the skeleton in the species.

Bone mineralization in male commercial broilers and its relationship to gait score

Decreased bone formation, mineralization, and enhanced resorption in calcium-deficient rats

OBJETIVO: Revisar os mecanismos de acoes dos glicocorticoides e sua capacidade de induzir osteoporose e deficits de crescimento. FONTES DOS DADOS: A revisao bibliografica de artigos cientificos foi realizada na base de dados MEDLINE e utilizou as palavras-chave agrupadas nas sintaxes “glicocorticoides”, “mineralizacao ossea”, “crescimento” e “efeitos colaterais”, nos ultimos 10 anos, e das referencias destes nos reportamos para as publicacoes mais antigas, mas com os estudos fundamentais para a compreensao do assunto. SINTESE DOS DADOS: Destacam-se acoes dos glicocorticoides sobre hormonios e citocinas responsaveis pelo crescimento longitudinal. Os efeitos finais dos glicocorticoides sobre o esqueleto sao determinados por acoes sistemicas no metabolismo osseo e por acoes diretas desses esteroides nas celulas osseas, levando a mudancas no numero e funcao das mesmas e favorecendo a perda ossea. Discutem-se os mecanismos indutores da recuperacao dos canais de crescimento e recuperacao da massa ossea apos a descontinuacao dos glicocorticoides; os metodos diagnosticos do metabolismo e mineralizacao ossea; assim como medidas terapeuticas e preventivas das alteracoes ossea induzidas pelos glicocorticoides. CONCLUSAO: A monitorizacao de cada paciente e essencial para identificacao e potencial reversao dos danos associados ao uso cronico de glicocorticoides.

Objective To verify the influence of body composition content and different distribution on bone age development, and establish a healthy lifestyle that benefits bone age development. Methods The prospective cohort study was conducted in the children aged 3 to 10 years at the outpatient and the body component analysis and bone age evaluation were tested during January 1st, 2014 to August 31th, 2015 at the Department of Child Health Care, Wuhan Children′s Hospital(Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science & Technology, and they were followed up for 1 year.During the follow-up of body weight, height, body composition and bone age, the effect of different body composition distribution and the increase rate on bone age development was investigated. Results Total 341 children were selected, of whom 166 cases were male, 175 cases were female, and their mean age were 3.3-10.8 years.The annual growth rate of bone age ranged from 0.62 to 1.37 years in different age groups.Adipose tissue was the fastest growing composition(2.60 kg/year), followed by lean body tissue(2.47 kg/year), while the slowest growing composition was bone mineral(0.14 kg/year). The prospective factors for fast bone age growth were the content of lean body tissue(β=14.13), skeletal muscle(β=12.79), bone minerals(β=6.26), salts(β=5.91) and lean body tissue of four limbs(1.74≤β≤20.79), longer circumferences of chest(β=2.02), abdomen(β=1.37), and left arms(β=1.36), more fat thickness of abdomen(β=13.10), right and left arms(β=9.47, 6.07)(all P<0.01). On the other hand, the obstructive factors of fast bone age growth were higher content of total body water(β=-5.99), extracellular fluid(β=-1.60), trunk lean body tissue(β=-7.67), and longer circum-ferences of right and left thighs(β=-1.81, -1.77), and high fat thickness of left thighs(β=-7.99)(all P<0.05). Conclusions A healthier lifestyle can defer bone development effectively, such as long-term aerobic exercise, less weight-bearing movement of the limbs (especially in upper limbs), and more water intake, which may result in a taller ultimate height. Key words: Child; Body component increasing velocity; Bone age development; Prospective study