Genetics of Bone Mass in Childhood and Adolescence: Effects of Sex and Maturation Interactions : GENETICS OF BONE MASS IN CHILDHOOD AND ADOLESCENCE

Low bone mass and strength lead to fragility fractures, for example, in elderly individuals affected by osteoporosis or children with osteogenesis imperfecta. A decade ago, rare human mutations affecting bone negatively (osteoporosis-pseudoglioma syndrome) or positively (high-bone mass phenotype, sclerosteosis and Van Buchem disease) have been identified and found to all reside in components of the canonical WNT signaling machinery. Mouse genetics confirmed the importance of canonical Wnt signaling in the regulation of bone homeostasis, with activation of the pathway leading to increased, and inhibition leading to decreased, bone mass and strength. The importance of WNT signaling for bone has also been highlighted since then in the general population in numerous genome-wide association studies. The pathway is now the target for therapeutic intervention to restore bone strength in millions of patients at risk for fracture. This paper reviews our current understanding of the mechanisms by which WNT signalng regulates bone homeostasis.

Background Readers may question the interpretation of findings in clinical trials when multiple outcome measures are used without adjustment of the p-value. This question arises because of the increased risk of Type I errors (findings of false "significance") when multiple simultaneous hypotheses are tested at set p-values. The primary aim of this study was to estimate the need to make appropriate p-value adjustments in clinical trials to compensate for a possible increased risk in committing Type I errors when multiple outcome measures are used. Discussion The classicists believe that the chance of finding at least one test statistically significant due to chance and incorrectly declaring a difference increases as the number of comparisons increases. The rationalists have the following objections to that theory: 1) P-value adjustments are calculated based on how many tests are to be considered, and that number has been defined arbitrarily and variably; 2) P-value adjustments reduce the chance of making type I errors, but they increase the chance of making type II errors or needing to increase the sample size. Summary Readers should balance a study's statistical significance with the magnitude of effect, the quality of the study and with findings from other studies. Researchers facing multiple outcome measures might want to either select a primary outcome measure or use a global assessment measure, rather than adjusting the p-value.

Decreased physical activity plays a critical role in the increase in childhood obesity. Although at least 60 minutes per day of moderate-to-vigorous physical activity (MVPA) is recommended, few longitudinal studies have determined the recent patterns of physical activity of youth. To determine the patterns and determinants of MVPA of youth followed from ages 9 to 15 years. Longitudinal descriptive analyses of the 1032 participants in the 1991-2007 National Institute of Child Health and Human Development Study of Early Child Care and Youth Development birth cohort from 10 study sites who had accelerometer-determined minutes of MVPA at ages 9 (year 2000), 11 (2002), 12 (2003), and 15 (2006) years. Participants included boys (517 [50.1%]) and girls (515 [49.9%]); 76.6% white (n = 791); and 24.5% (n = 231) lived in low-income families. Mean MVPA minutes per day, determined by 4 to 7 days of monitored activity. At age 9 years, children engaged in MVPA approximately 3 hours per day on both weekends and weekdays. Weekday MVPA decreased by 37 minutes per year [corrected], while weekend MVPA decreased by 39 minutes per year [corrected]. By age 15 years, adolescents were only engaging in MVPA for 50 minutes per weekday [corrected] and 36 minutes per weekend day [corrected]. Boys were more active than girls, spending 18 and 14 more minutes per day [corrected] in MVPA on the weekdays and weekends, respectively. The rate of decrease in MVPA was the same for boys and girls. The estimated age at which girls crossed below the recommended 60 minutes of MVPA per day was approximately 13.2 years for weekday [corrected] activity compared with boys at 14.9 years [corrected], and for weekend activity, girls crossed below the recommended 60 minutes of MVPA at 12.7 years [corrected] compared with boys at 13.6 years [corrected]. In this study cohort, measured physical activity decreased significantly between ages 9 and 15 years.