Melonie Burrows

Physical activity positively predicts bone architecture and bone strength in adolescent males and females.

Aims:  Physical activity (PA) has positive effects on bone accrual and geometry in children during growth. However, we do not know how PA influences adaptations in bone architecture during growth. We evaluated the contribution of PA to bone density, architecture and strength in adolescents.

International longitudinal pediatric reference standards for bone mineral content

To render a diagnosis pediatricians rely upon reference standards for bone mineral density or bone mineral content, which are based on cross-sectional data from a relatively small sample of children. These standards are unable to adequately represent growth in a diverse pediatric population. Thus, the goal of this study was to develop sex and site-specific standards for BMC using longitudinal data collected from four international sites in Canada and the United States. Data from four studies were combined; Saskatchewan Paediatric Bone Mineral Accrual Study (n=251), UBC Healthy Bones Study (n=382); Penn State Young Womens Health Study (n=112) and Stanfords Bone Mineral Accretion study (n=423). Males and females (8 to 25 years) were measured for whole body (WB), total proximal femur (PF), femoral neck (FN) and lumbar spine (LS) BMC (g). Data were analyzed using random effects models. Bland-Altman was used to investigate agreement between predicted and actual data. Age, height, weight and ethnicity independently predicted BMC accrual across sites (P<0.05). Compared to White males, Asian males had 31.8 (6.8) g less WB BMC accrual; Hispanic 75.4 (28.2) g less BMC accrual; Blacks 82.8 (26.3) g more BMC accrual with confounders of age, height and weight controlled. We report similar findings for the PF and FN. Models for females for all sites were similar with age, height and weight as independent significant predictors of BMC accrual (P<0.05). We provide a tool to calculate a childs BMC Z-score, accounting for age, size, sex and ethnicity. In conclusion, when interpreting BMC in pediatrics we recommend standards that are sex, age, size and ethnic specific.

Assessing Bone Microstructure at the Distal Radius in Children and Adolescents Using HR-pQCT: A Methodological Pilot Study

We examined the use of high-resolution peripheral quantitative computed tomography (HR-pQCT [XtremeCT; Scanco Medical, Switzerland]) to assess bone microstructure at the distal radius in growing children and adolescents. We examined forearm radiographs from 37 children (age 8-14 yr) to locate the position of the ulnar and radial growth plates. We used HR-pQCT to assess bone microstructure in a region of interest (ROI) at the distal radius that excluded the growth plate (as determined from the radiographs) in all children (n=328; 9-21 yr old). From radiographs, we determined that a ROI in the distal radius at 7% of bone length excluded the radial growth plate in 100% of participants. We present bone microstructure data at the distal radius in children and adolescents. From the HR-pQCT scans, we observed active growth plates in 80 males (aged 9.5-20.7 yr) and 92 females (aged 9.5-20.2 yr). The ulnar plate was visible in 9 male and 17 female participants (aged 11.2 ± 1.9yr). The HR-pQCT scan required 3 min with a relatively low radiation dose (<3 μSv). Images from the radial ROI were free of artifacts and outlined cortical and trabecular bone microstructure. There is currently no standard method for these measures; therefore, these findings provide insight for investigators using HR-pQCT for studies of growing children.

Bone and Muscle Parameters of the Tibia: Agreement Between the XCT 2000 and XCT 3000 Instruments

Peripheral quantitative computed tomography is a valuable tool to assess bone in children across growth, with long-term studies capturing nuances missed in cross-sectional studies. As children grow, a change from XCT 2000 to a XCT 3000 may be required to accommodate the increasing size of the lower limbs. We examined the precision and agreement between the Stratec XCT 2000 and 3000 on selected bone and muscle parameters. Twenty-eight participants (mean+/-SD; age 27.5+/-6.5 yr) underwent scans at the distal (8%), mid (50%), and proximal (66%) tibia sites, to assess total bone area, total bone density, and trabecular density (8% site); and total bone area, cortical area, cortical density (CoD), polar strength-strain index, and muscle cross-sectional area (50% and 66% sites). Outcomes between instruments were highly correlated; r=0.90-0.99 for CoD across sites, with r=0.97-0.99 for all other measures. Bland and Altman plots showed excellent agreement between instruments for all variables. Regression indicated no significant relationship between instrument and size of measurement (p>0.05). Coefficients of variation were lower than previously reported (0.4-2.4%). For longitudinal studies, the XCT 3000 can replace the XCT 2000 with minimal influence on bone and muscle parameters.

The generalized bone phenotype in children with neurofibromatosis 1: A sibling matched case–control study

People with neurofibromatosis 1 (NF1) have low bone mineralization, but the natural history and pathogenesis are poorly understood. We performed a sibling‐matched case–control study of bone mineral status, morphology, and metabolism. Eighteen children with NF1 without focal bony lesions were compared to unaffected siblings and local population controls. Bone mineral content at the lumbar spine and proximal femur (dual energy X‐ray absorptiometry (DXA)) was lower in children with NF1; this difference persisted after adjusting for height and weight. Peripheral quantitative computed tomography (pQCT) of the distal tibia showed that trabecular density was more severely compromised than cortical. Peripheral QCT‐derived estimates of bone strength and resistance to bending and stress were poorer among children with NF1 although there was no difference in fracture frequencies. There were no differences in the size or shape of bones after adjusting for height. Differences in markers of bone turnover between cases and controls were in the directions predicted by animal studies, but did not reach statistical significance. Average serum calcium concentration was higher (although within the normal range) in children with NF1; serum 25‐OH vitamin D, and PTH levels did not differ significantly between cases and controls. Children with NF1 were less mature (assessed by pubertal stage) than unaffected siblings or population controls. Children with NF1 have a generalized difference of bone metabolism that predominantly affects trabecular bone. Effects of decreased neurofibromin on bone turnover, calcium homeostasis, and pubertal development may contribute to the differences in bone mineral content observed among people with NF1.