Objectives: No nationwide paediatric reference standards for bone mineral density (BMD) are available in China. We aimed to provide sex-specific BMD reference values for Chinese children and adolescents (3-18 years). Methods: Data (10 818 participants aged 3-18 years) were obtained from cross-sectional surveys of the China Child and Adolescent Cardiovascular Health in 2015, which included four municipality cities and three provinces. BMD was measured using Hologic Discovery Dual Energy X-ray Absorptiometry (DXA) scanner. The DXA measures were modelled against age, with height as an independent variable. The LMS statistical method using a curve fitting procedure was used to construct reference smooth cross-sectional centile curves for dependent versus independent variables. Results: Children residing in Northeast China had the highest total body less head (TBLH) BMD while children residing in Shandong Province had the lowest values. Among children, TBLH BMD was higher for boys as compared with girls; but, it increased with age and height in both sexes. Furthermore, TBLH BMD was higher among US children as compared with Chinese children. There was a large difference in BMD for height among children from these two countries. US children had a much higher BMD at each percentile (P) than Chinese children; the largest observed difference was at P50 and P3 and the smallest difference was at P97. Conclusions: This is the first study to present a sex-specific reference dataset for Chinese children aged 3-18 years. The data can help clinicians improve interpretation, assessment and monitoring of densitometry results.

Background: It has been reported that dancers are at greater risk of developing low bone mineral density (BMD) compared to general population; however, some published studies also highlight the positive effects of dance training on bone metabolism. Given the existing controversy, the aim of the current work was a) to investigate bone health status of professional ballet dancers and vocational dance students, and b) to investigate associated factors and mechanisms involved in dancers’ bone health. Design Cross-sectional, longitudinal analysis (2-yrs follow-up) and genetic association studies were conducted on a population which consisted of professional ballet dancers, vocational dance students and controls. Methods: The total of 58 professional ballet dancers (66 sex- aged-matched controls), and 152 vocational dance students (96 aged- and sex-matched controls) were screened for BMD status at impact [femoral neck (FN); lumbar spine (LS)] and non-impact sites (forearm). Tanner staging, age at menarche and menstrual status were assessed via questionnaires. Bone mass, nutrition, peak height velocity estimation, energy availability, insulin-like growth factor I (IGF-1), oestrogens, growth hormone, and sclerostin serum concentrations were longitudinally measured in a sub-sample of 101 vocational dance students and age- and sex-matched controls. Association between polymorphisms of the Wnt/β-catenin and ER signalling pathways with low BMD were further investigated. Results: Female vocational dance students were more likely to display low BMD at the forearm and LS than controls (OR= 0.1; p < 0.05 and OR=0.2; p < 0.05, respectively); the prevalence of low BMD at the forearm was significantly higher in female professional ballet dancers than controls (37.5% vs. 17.4%, p < 0.001). During the follow-up, both female and male vocational dancers revealed significantly lower BMD at impact and non-impact sites (p < 0.001) compared to controls. Serum IGF-1 concentrations were significantly increased in vocational dancers compared to controls at 2yrs follow-up (p < 0.05), as well as serum sclerostin (p < 0.05). Genetic variants at the Wnt/β-catenin and ER signalling pathways were identified as risk factors for low BMD at both impact and non-impact sites. Conclusion: Professional dancers and vocational dance students have lower bone health compared to controls. Genetic mechanisms seem to be determinant. It is recommend that dancers performing at elite level should be referred for bone densitometry.

This study was conducted to determine if physical activity and cardiorespiratory fitness (CRF) at baseline influence the likelihood of gaining bone mineral density (BMD) at the hip and lumbar spine over 6 years. Another aim was to ascertain the effect of several potential confounding factors. In a prospective study of 244 women (baseline age range 35-45 years), physical activity volume (PAv) and intensity (PAi) were measured using accelerometers at baseline. CRF indexed by VO2max was estimated using a graded, maximal treadmill test at baseline. BMD was measured using DEXA. Risk ratios were used to show the likelihood of BMD gains (> 75th percentile) between different levels of PAv, PAi, or CRF at baseline. Mean hip BMD change was -0.015 + 0.045 g/cm2. Women with high PAv were 2.50 times (95% CI: 1.19-5.24), and women with moderate PAv were 2.20 times (95% CI: 1.08-4.45), more likely to experience significant hip BMD gains than women with low PAv. Adjusting for potential confounders had little effect on the results. Baseline PAi and CRF were not related to changes in hip BMD. None of the relationships between PAv, PAi, and CRF, and changes in spine BMD, was statistically significant. Middle-aged women with moderate or high levels of PAv are more likely to experience significant gains in hip BMD over time compared to those with low levels of PAv.

La dystrophine est une très grande protéine codée le gène DMD et située sous la membrane plasmique des fibres musculaires. Elle joue un rôle essentiel dans le maintien de l’intégrité de la cellule musculaire lors des cycles de contraction/relaxation. Cette protéine filamenteuse est composée de quatre domaines structuraux dont le domaine central composé de 24 répétitions homologues à la spectrine. Chaque répétition est organisée en faisceau de trois α-hélices appelé « coiled-coil ». Des mutations du gène DMD sont à l’origine des myopathies de Duchenne (DMD) et de Becker (BMD) qui s’accompagnent d’un déficit total ou d’une dystrophine mutée et induisent de ruptures fréquentes de la membrane des cellules musculaires. La connaissance de la structure de la dystrophine est nécessaire au développement de thérapies à ce jour inexistantes pour les myopathies. Au laboratoire, des données structurales du domaine central de la dystrophine ont été acquises par diffusion des rayons X aux petits angles (SAXS, Small Angles X-ray Scattering). Cette thèse présente le développement d’une approche multi-échelle combinant des données expérimentales SAXS et des données in silico pour la reconstruction de modèles haute-résolution des fragments du domaine central de la dystrophine et d’un fragment muté observé dans une mutation BMD fréquente. Nous avons également cartographié l’interaction de ce domaine central avec deux de ses partenaires fonctionnels importants, l’actine filamenteuse et avec la nitroxyde synthase neuronale (nNOS) et proposé les premiers modèles atomiques des complexes macromoléculaires correspondants. L’ensemble de ces résultats permettra à terme l’optimisation de thérapies pour le traitement des dystrophies musculaires. / Dystrophin is a large protein encoded by DMD gene and located under the plasma membrane of muscle fibers. It plays an essential role in maintaining the integrity of muscle cells during contraction/relaxation cycles. This filamentous protein is composed of four structural domains including the central domain consisting of 24 spectrin-like repeats and four hinges. Each repetition is folded in three α-helices in a ‘coiled-coil’ assembly. Mutations in the DMD gene leads to Duchenne muscular dystrophy (DMD) and Becker (MDBs), which are accompanied by frequent plasma membrane ruptures, due to the loss or modification of dystrophin protein. There are very few structural data available concerning the central domain of dystrophin, which is subject to many mutations involved in DMD and BMD diseases. However, the description and the understanding to an atomic level of dystrophin structure and its interaction is essential for optimization of therapies. Given the impossibility to solve its structure by X-ray crystallography or NMR, structural data of the dystrophin central domain were acquired by small angles X-rays scattering (SAXS, Small Angles X-ray Scattering). This thesis presents the development of an innovative multi-scale approach combining experimental SAXS and in silico derived data, allowing the reconstruction of high-resolution models of dystrophin central domain fragments. Structural data were also obtained on a mutated dystrophin frequently observed in BMDs. Furthermore, we also mapped the interactions of the central domain with two of its majors functional partners, Filamentous actin and neuronal nitroxyde synthase (nNOS) and proposed models of the related macromolecular complexes. At long-term, all of these results will allow optimization of therapies for the treatment of muscular dystrophies.

No description available.

abstract: The overall goal of this research project was to assess the feasibility of investigating the effects of microgravity on mineralization systems in unit gravity environments. If possible to perform these studies in unit gravity earth environments, such as earth, such systems can offer markedly less costly and more concerted research efforts to study these vitally important systems. Expected outcomes from easily accessible test environments and more tractable studies include the development of more advanced and adaptive material systems, including biological systems, particularly as humans ponder human exploration in deep space. The specific focus of the research was the design and development of a prototypical experimental test system that could preliminarily meet the challenging design specifications required of such test systems. Guided by a more unified theoretical foundation and building upon concept design and development heuristics, assessment of the feasibility of two experimental test systems was explored. Test System I was a rotating wall reactor experimental system that closely followed the specifications of a similar test system, Synthecon, designed by NASA contractors and thus closely mimicked microgravity conditions of the space shuttle and station. The latter includes terminal velocity conditions experienced by both innate material systems, as well as, biological systems, including living tissue and humans but has the ability to extend to include those material test systems associated with mineralization processes. Test System II is comprised of a unique vertical column design that offered more easily controlled fluid mechanical test conditions over a much wider flow regime that was necessary to achieving terminal velocities under free convection-less conditions that are important in mineralization processes. Preliminary results indicate that Test System II offers distinct advantages in studying microgravity effects in test systems operating in unit gravity environments and particularly when investigating mineralization and related processes. Verification of the Test System II was performed on validating microgravity effects on calcite mineralization processes reported earlier others. There studies were conducted on calcite mineralization in fixed-wing, reduced gravity aircraft, known as the `vomit comet' where reduced gravity conditions are include for very short (~20second) time periods. Preliminary results indicate that test systems, such as test system II, can be devised to assess microgravity conditions in unit gravity environments, such as earth. Furthermore, the preliminary data obtained on calcite formation suggest that strictly physicochemical mechanisms may be the dominant factors that control adaptation in materials processes, a theory first proposed by Liu et al. Thus the result of this study may also help shine a light on the problem of early osteoporosis in astronauts and long term interest in deep space exploration. / Dissertation/Thesis / M.S. Bioengineering 2013

The primary function of vitamin D in humans is to maintain sufficient circulating calcium concentrations. Low vitamin D levels could result in excessive calcium resorption from bone. Vitamin deficiency may therefore decrease bone mineral density (BMD), resulting in an increased risk of fracture. This thesis sought to determine the association between vitamin D intake and bone health and to estimate circulating levels of vitamin D optimal for bone health without increasing the risk for non-bone disease. Furthermore, the thesis assessed the difference in performance between common serum vitamin D assays and the genetic influence of vitamin D status. In prospective population-based cohorts, blood concentrations &lt;40 nmol/L (lowest 5%) increased the risk of fracture in elderly men. Low levels were further associated with a slight decrease in lumbar spine BMD. Both high (&gt;98 nmol/L) and low (&lt;46 nmol/L) vitamin D levels were associated with higher cancer and overall mortality. In another cohort, also of older men and women, no association was found between vitamin D levels and fracture. Low vitamin D levels were weakly associated with decreased total body BMD in men but not in women. Dietary intake of vitamin D over a 20-year period in more than 60,000 Swedish women was not associated with osteoporosis or fracture, regardless of calcium intake. During summer, dietary vitamin D intake and other life style habits are of minor importance for the variation in vitamin D levels relative to sun exposure and genes. In summer time, genes explain about half  of the variation in vitamin D levels, but none of the variance in winter time. The variability between vitamin D assays was substantial. Three assays classified 8, 22 and 43% of the same study population as vitamin D insufficient if &lt;50 nmol/L was set as the insufficiency level. Based on the results in this thesis, low 25(OH)D levels and low dietary vitamin D intake are not a major cause of fractures in community-dwelling elderly Swedish women and men. Differences in assay performance and potential negative health outcomes of high 25(OH)D levels need to be considered.

Background: Osteoporosis has become a major problem worldwide as the population ages. An osteoporotic fracture is associated with a high rate of morbidity and mortality. Data on the prevalence, risk factors and outcome of osteoporotic fractures in South Africa remains sparse. Method: A retrospective audit was undertaken in all patients attending the Endocrine Clinic at Groote Schuur Hospital between March 2019 and March 2020 for the treatment of osteoporosis. Patients folders were reviewed to obtain the following information: demographic data, risk factors, laboratory investigations, treatment, baseline and follow up DEXA scans. Results: 264 patients were evaluated, average age 65.7 ± 12.3 years, 92.8% (n=245) were female. Common risk factors included smoking (50.8%, n=134), vitamin D deficiency (29.2%, n=77), steroid use (21.6%, n=57) and primary hyperparathyroidism (15.2%, n=40). A fragility fracture was diagnosed in 68.6% (n=181) - vertebral only (54.7%, n=99), hip only (14.9%, n=27), vertebral and hip (10.5%, n=19), wrist (7.2%, n=13) and other (12.7%, n=23). Bisphosphonates were used by 75% (n=198) of patients at the time of enrolment. Of these, 80.8% (n=160) received intravenous zoledonic acid alone, 6.1% (n=12) received oral alendronate alone and 13.1% (n=26) initially received alendronate followed by intravenous zoledronic acid. Over 5.2 years there was an improvement in bone mineral density (BMD) of 4.4% at the lumbar spine, while there was slight worsening of BMD at the femoral neck (- 0.17%). A fracture whilst on treatment occurred in 10.6% (n=21) of patients. Conclusion: The majority of patients with osteoporosis at Groote Schuur Hospital had a fragility fracture at diagnosis with a vertebral fracture being most common. Bisphosphonate treatment showed a measurable improvement in BMD at the lumbar spine, however, there was no improvement at the femoral neck. Despite this, few patients had a symptomatic vertebral or hip fracture whilst on treatment.

No description available.

Seconde espèce de mollusque bivalve la plus exploitée au monde, la palourde japonaise Venerupis philippinarum représente un intérêt économique majeur. A l’échelle du bassin d’Arcachon, la maladie du muscle marron ou BMD (pour Brown Muscle Disease), pathologie émergente découverte en 2005 inquiète tout particulièrement le secteur de la pêche. Cette pathologie affecte le muscle adducteur postérieur de la palourde et perturbe l’ouverture-fermeture des valves. Cette perturbation entraine la remontée des individus à la surface du sédiment et la mort.Ces travaux de thèse ont porté d’une part sur l’épizootiologie de la maladie et son impact sur l'hôte et d’autre part sur l’identification de l’agent responsable de la maladie.Une étude sur la distribution des palourdes dans le bassin d’Arcachon (littoral Atlantique français) montre que la prévalence de la BMD a diminué entre 2010 et 2012. Toutefois cette baisse ne concerne pas les individus ayant atteint la taille légale de pêche (> 35mm). De plus, la maladie semble apparaitre chez des individus de plus en plus petit et risque donc d’accroitre la mortalité aux plus jeunes stades. L’analyse des facteurs environnementaux impliqués dans la distribution de la maladie souligne la corrélation entre la prévalence de la BMD et un hydrodynamisme relativement « calme ».La BMD affecte tout particulièrement le métabolisme énergétique de l’hôte, les mécanismes de réponse au stress oxydant et également le système immunitaire. De nombreuses fonctions sont surexprimées chez les hôtes malades mais d’autres voies comme celle de l’apoptose sont régulées négativement par l’agent infectieux.Si l’origine virale est maintenant une hypothèse solide (microscopie électronique, transcriptomique), la nature exacte de l’agent étiologique (famille virale) ne peut à ce jour être déterminée avec certitude. Des particules virales ont bien été observées dans les tissus malades mais pas dans les tissus sains, et ont pu être purifiées sur gradient de sucrose. Toutefois, les essais pour provoquer la maladie chez des individus sains ont échoué. / The Manila clam Venerupis philippinarum is the second most exploited mollusk bivalve in the world and represents a major economic interest. At the scale of Arcachon bay, the Brown Muscle Disease or BMD, an emergent pathology discovered in 2005, concerns fishing activity. This pathology affects the posterior adductor muscle of the clam and disrupts the valve opening and closing process. It induces the migration of clams to the surface and their death.This thesis concerns on the one hand the epizootiology of the disease and its impact on host and on the other hand the identification of the causal agent of the disease. A study of the clam distribution in Arcachon bay (French Atlantic coast) shows that prevalence of BMD decreased between 2010 and 2012. However this decrease doesn't affect clams of the legal harvesting size (> 35mm). Furthermore, the disease seems to appear in individuals with increasingly smaller size and thus risks to increase mortality in the youngest stages. The analysis of the environmental factors that are involved in the disease distribution highlights the correlation between prevalence of the BMD and relatively "quiet" hydrodynamism.BMD particularly affects the energy metabolism of the host, the oxidative stress response mechanisms and the immune system.Many functions are up-regulated in the BMD-affected hosts but other ways, as the apoptosis, are down-regulated by the infectious agent.Although viral origin of BMD is now a convincing hypothesis (electronic microscopy, transcriptomic), the nature of the etiological agent (viral family) cannot so far be determined with certainty. Viral particles were observed in tissues of BMD-diseased hosts but not in tissues of healthy host. They have been purified on sucrose gradient. However, the attempt to provoke the disease in healthy individuals failed.