Lumbar spine and total-body dual-energy X-ray absorptiometry in children with severe neurological impairment and intellectual disability: a pilot study of artefacts and disrupting factors

Background Children with severe neurological impairment and intellectual disability (ID) are susceptible for developing low bone mineral density (BMD) and fractures. BMD is generally measured with dual-energy X-ray absorptiometry (DXA). Objective To describe the occurrence of factors that may influence the feasibility of DXA and the accuracy of DXA outcome in children with severe neurological impairment and ID. Materials and methods Based on literature and expert opinion, a list of disrupting factors was developed. Occurrence of these factors was assessed in 27 children who underwent DXA measurement. Results Disrupting factors that occurred most frequently were movement during measurement (82%), aberrant body composition (67%), small length for age (56%) and scoliosis (37%). The number of disrupting factors per child was mean 5.3 (range 1-8). No correlation was found between DXA outcomes and the number of disrupting factors. Conclusion Factors that may negatively influence the accuracy of DXA outcome are frequently present in children with severe neurological impairment and ID. No systematic deviation of DXA outcome in coherence with the amount of disrupting factors was found, but physicians should be aware of the possible influence of disrupting factors on the accuracy of DXA

A paediatric bone index derived by automated radiogrammetry

Hand radiographs are obtained routinely to determine bone age of children. This paper presents a method that determines a Paediatric Bone Index automatically from such radiographs. The Paediatric Bone Index is designed to have minimal relative standard deviation (7.5%), and the precision is determined to be 1.42%. Introduction We present a computerised method to determine bone mass of children based on hand radiographs, including a reference database for normal Caucasian children. Methods Normal Danish subjects (1,867), of ages 7-17, and 531 normal Dutch subjects of ages 5-19 were included. Historically, three different indices of bone mass have been used in radiogrammetry all based on A = pi TW(1 - T/W), where T is the cortical thickness and W the bone width. The indices are the metacarpal index A/W-2, DXR-BMD=A/W, and Exton-Smith's index A/(WL), where L is the length of the bone. These indices are compared with new indices of the form A/((WLb)-L-a), and it is argued that the preferred index has minimal SD relative to the mean value at each bone age and sex. Finally, longitudinal series of X-rays of 20 Japanese children are used to derive the precision of the measurements. Results The preferred index is A/((WL0.33)-L-1.33), which is named the Paediatric Bone Index, PBI. It has mean relative SD 7.5% and precision 1.42%. Conclusions As part of the BoneXpert method for automated bone age determination, our method facilitates retrospective research studies involving validation of the proposed index against fracture incidence and adult bone mineral densit

The mode of school transportation in pre-pubertal children does not influence the accrual of bone mineral or the gain in bone size - two year prospective data from the paediatric osteoporosis preventive (POP) study

<p>Abstract</p> <p>Background</p> <p>Walking and cycling to school are one source of regular physical activity. The aim of this two years observational study in pre-pubertal children was to evaluate if walking and cycling to school was associated with higher total amount of physical activity and larger gain in bone mineral content (BMC) and bone width than when going by car or bus.</p> <p>Methods</p> <p>133 boys and 99 girls aged 7-9 years were recruited to the Malmö Prospective Paediatric Osteoporosis Prevention (POP) study. BMC (g) was measured by dual X-ray absorptiometry (DXA) in total body, lumbar spine (L2-L4) and femoral neck (FN) at baseline and after 24 months. Bone width was measured in L2-L4 and FN. Skeletal changes in the 57 boys and 48 girls who consistently walked or cycled to school were compared with the 24 boys and 17 girls who consistently went by bus or car. All children remained in Tanner stage I. Level of everyday physical activity was estimated by accelerometers worn for four consecutive days and questionnaires. Comparisons were made by independent student's t-tests between means and Fisher's exact tests. Analysis of covariance (ANCOVA) was used to adjust for group differences in age at baseline, duration of organized physical activity, annual changes in length and BMC or bone width if there were differences in these traits at baseline.</p> <p>Results</p> <p>After the adjustments, there were no differences in the annual changes in BMC or bone width when comparing girls or boys who walked or cycled to school with those who went by car or bus. Furthermore, there were no differences in the levels of everyday physical activity objectively measured by accelerometers and all children reached above the by the United Kingdom Expert Consensus Group recommended level of 60 minutes moderate to vigorous physical activity per day.</p> <p>Conclusion</p> <p>A physical active transportation to school for two years is in pre-pubertal children not associated with a higher accrual of BMC or bone width than a passive mode of transportation, possibly due to the fact that the everyday physical activity in these pre-pubertal children, independent of the mode of school transportation, was high.</p

A one-year exercise intervention program in pre-pubertal girls does not influence hip structure

<p>Abstract</p> <p>Background</p> <p>We have previously reported that a one-year school-based exercise intervention program influences the accrual of bone mineral in pre-pubertal girls. This report aims to evaluate if also hip structure is affected, as geometry independent of bone mineral influences fracture risk.</p> <p>Methods</p> <p>Fifty-three girls aged 7 – 9 years were included in a curriculum-based exercise intervention program comprising 40 minutes of general physical activity per school day (200 minutes/week). Fifty healthy age-matched girls who participated in the general Swedish physical education curriculum (60 minutes/week) served as controls. The hip was scanned by dual X-ray absorptiometry (DXA) and the hip structural analysis (HSA) software was applied to evaluate bone mineral content (BMC), areal bone mineral density (aBMD), periosteal and endosteal diameter, cortical thickness, cross-sectional moment of inertia (CSMI), section modulus (Z) and cross-sectional area (CSA) of the femoral neck (FN). Annual changes were compared. Group comparisons were done by independent student's <it>t</it>-test between means and analyses of covariance (ANCOVA). Pearson's correlation test was used to evaluate associations between activity level and annual changes in FN. All children remained at Tanner stage 1 throughout the study.</p> <p>Results</p> <p>No between-group differences were found during the 12 months study period for changes in the FN variables. The total duration of exercise during the year was not correlated with the changes in the FN traits.</p> <p>Conclusion</p> <p>Evaluated by the DXA technique and the HSA software, a general one-year school-based exercise program for 7–9-year-old pre-pubertal girls seems not to influence the structure of the hip.</p

Pediatric DXA: clinical applications

Normal bone mineral accrual requires adequate dietary intake of calcium, vitamin D and other nutrients; hepatic and renal activation of vitamin D; normal hormone levels (thyroid, parathyroid, reproductive and growth hormones); and neuromuscular functioning with sufficient stress upon the skeleton to induce bone deposition. The presence of genetic or acquired diseases and the therapies that are used to treat them can also impact bone health. Since the introduction of clinical DXA in pediatrics in the early 1990s, there has been considerable investigation into the causes of low bone mineral density (BMD) in children. Pediatricians have also become aware of the role adequate bone mass accrual in childhood has in preventing osteoporotic fractures in late adulthood. Additionally, the availability of medications to improve BMD has increased with the development of bisphosphonates. These factors have led to the increased utilization of DXA in pediatrics. This review summarizes much of the previous research regarding BMD in children and is meant to assist radiologists and clinicians with DXA utilization and interpretation

Deciphering von Hippel-Lindau (VHL/Vhl)-Associated Pancreatic Manifestations by Inactivating Vhl in Specific Pancreatic Cell Populations

The von Hippel-Lindau (VHL) syndrome is a pleomorphic familial disease characterized by the development of highly vascularized tumors, such as hemangioblastomas of the central nervous system, pheochromocytomas, renal cell carcinomas, cysts and neuroendocrine tumors of the pancreas. Up to 75% of VHL patients are affected by VHL-associated pancreatic lesions; however, very few reports in the published literature have described the cellular origins and biological roles of VHL in the pancreas. Since homozygous loss of Vhl in mice resulted in embryonic lethality, this study aimed to characterize the functional significance of VHL in the pancreas by conditionally inactivating Vhl utilizing the Cre/LoxP system. Specifically, Vhl was inactivated in different pancreatic cell populations distinguished by their roles during embryonic organ development and their endocrine lineage commitment. With Cre recombinase expression directed by a glucagon promoter in α-cells or an insulin promoter in β-cells, we showed that deletion of Vhl is dispensable for normal functions of the endocrine pancreas. In addition, deficiency of VHL protein (pVHL) in terminally differentiated α-cells or β-cells is insufficient to induce pancreatic neuroendocrine tumorigenesis. Most significantly, we presented the first mouse model of VHL-associated pancreatic disease in mice lacking pVHL utilizing Pdx1-Cre transgenic mice to inactivate Vhl in pancreatic progenitor cells. The highly vascularized microcystic adenomas and hyperplastic islets that developed in Pdx1-Cre;Vhl f/f homozygous mice exhibited clinical features similar to VHL patients. Establishment of three different, cell-specific Vhl knockouts in the pancreas have allowed us to provide evidence suggesting that VHL is functionally important for postnatal ductal and exocrine pancreas, and that VHL-associated pancreatic lesions are likely to originate from progenitor cells, not mature endocrine cells. The novel model systems reported here will provide the basis for further functional and genetic studies to define molecular mechanisms involved in VHL-associated pancreatic diseases