MAFFEIS, CLAUDIO, ANGELO PIETROBELLI, ALESSANDRA GREZZANI, SILVIA PROVERA, AND LUCIANO TATÒ . Waist circumference and cardiovascular risk factors in prepubertal children. Obes Res. 2001;9: 179 -187. Objective: Intra-abdominal fat has been identified as being the most clinically relevant type of fat in humans. Therefore, an assessment of body-fat distribution could possibly identify subjects with the highest risk of adverse lipid profile and hypertension. Few data on the relationship between body-fat distribution and cardiovascular risk factors are available in children, especially before puberty. Research Methods and Procedures:This cross-sectional study was undertaken to explore the relationship between anthropometric variables, lipid concentrations, and blood pressure (BP) in a sample of 818 prepubertal children (ages 3 to 11 years) and to assess the clinical relevance of waist circumference in identifying prepubertal children with higher cardiovascular risk. Height, weight, triceps and subscapular skinfolds, waist circumference, and BP were measured. Plasma levels for triacylglycerol, total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein cholesterol, apolipoprotein A1 (ApoA1), and apolipoprotein B (ApoB) were determined. Results: Females were fatter than males (5.8 [3.5] vs. 4.8 [3.3] kg of fat mass; p Ͻ 0.01). Males had higher HDL cholesterol and ApoA1/ApoB plasma concentrations than females (p Ͻ 0.001 and p Ͻ 0.01, respectively). Waist circumference had a higher correlation with systolic and diastolic BP (r ϭ 0.40 and 0.29, respectively; p Ͻ 0.001) than triceps (r ϭ 0.35 and 0.21, respectively; p Ͻ 0.001) and subscapular (r ϭ 0.28 and 0.16, respectively; p Ͻ 0.001) skinfolds and relative body weight (0.33 and 0.23, respectively; p Ͻ 0.001). Multivariate linear model analysis showed that ApoA1/ApoB, HDL cholesterol, total cholesterol/HDL cholesterol, and systolic as well as diastolic BP were significantly associated with waist circumference and triceps and subscapular skinfolds, independently of age, gender, and body mass index. Discussion: Waist circumference as well as subscapular and triceps skinfolds may be helpful parameters in identifying prepubertal children with an adverse blood-lipids profile and hypertension. However, waist circumference, which is easy to measure and more easily reproducible than skinfolds, may be considered in clinical practice. Children with a waist circumference greater than the 90th percentile are more likely to have multiple risk factors than children with a waist circumference that is less than or equal to the 90th percentile.

The parents' obesity was the main risk factor for obesity in this group of children. Sedentary behaviour (TV viewing) was independently associated with overweight at the age of 8 y. Physical activity and energy and nutrient intakes did not significantly affect the change in rel BMI over the four-year period when the parents' obesity was taken into account.

Purpose: A clinical trial was conducted to evaluate the safety and efficacy of alglucosidase alfa in infants and children with advanced Pompe disease. Methods: Open-label, multicenter study of IV alglucosidase alfa treatment in 21 infants 3-43 months old (median 13 months) with minimal acid ␣-glucosidase activity and abnormal left ventricular mass index by echocardiography. Patients received IV alglucosidase alfa every 2 weeks for up to 168 weeks (median 120 weeks). Survival results were compared with an untreated reference cohort. Results: At study end, 71% (15/21) of patients were alive and 44% (7/16) of invasive-ventilator free patients remained so. Compared with the untreated reference cohort, alglucosidase alfa reduced the risk of death by 79% (P Ͻ 0.001) and the risk of invasive ventilation by 58% (P ϭ 0.02). Left ventricular mass index improved or remained normal in all patients evaluated beyond 12 weeks; 62% (13/21) achieved new motor milestones. Five patients were walking independently at the end of the study and 86% (18/21) gained functional independence skills. Overall, 52% (11/21) of patients experienced infusion-associated reactions; 95% (19/20) developed IgG antibodies to recombinant human lysosomal acid ␣-glucosidase; no patients withdrew from the study because of safety concerns. Conclusions: In this population of infants with advanced disease, biweekly infusions with alglucosidase alfa prolonged survival and invasive ventilation-free survival. Treatment also improved indices of cardiomyopathy, motor skills, and functional independence. Genet Med 2009:11(3):210-219.

In a randomized controlled study, we investigated the effect of treatment with intravenous neridronate in prepubertal children with OI. Our study suggests that quarterly intravenous infusions of the bisphosphonate significantly raise the rate of increase in BMD at both the spine and hip, the projected area of the lumbar vertebrae, and height. These results are associated with a significant decrease in the risk of clinical fractures.Introduction: Osteogenesis imperfecta (OI) is a heritable disease of connective tissue, characterized by increased bone fragility. Bisphosphonates currently seem to be the most promising therapy, but randomized, controlled studies are scarce and have never been carried out in prepubertal children. Materials and Methods:This was a randomized, controlled 3-year clinical trial. The Italian Patients' Society of OI (AsItOI) sent their members affected by any type of OI to two centers at the University of Verona (Italy) to participate in the study. Sixty-four children, 6-11 years of age for boys and 6-9 years of age for girls, with no signs of puberty and who were never treated with bisphosphonates, were randomized to either intravenous neridronate (2 mg/kg infused IV in 30 minutes every 3 months) or no treatment, with a ratio of 2:1. Control patients were given the same bisphosphonate therapy at the end of the first year. BMD and projected bone areas, as measured by DXA, at spine and hip, height, and peripheral fracture incidence, both prospective and retrospective (2 years preceding randomization), were the main outcomes of the study. Results: At the end of the first year, spine and hip BMD rose by 3.5-5.7% in control patients and by 18-25% (p < 0.001 versus controls) in the active group, respectively. During the following 2 years, the treatment in all patients was associated with BMD increases of 10-25% per year. Height and the DXA-derived projected area of lumbar spine rose during the first year of observation significantly more in the active group than in the control group (<0.01 and <0.05, respectively). Both height and spine projected area continued to rise in the treated patients toward levels found in healthy individuals. During the first year of treatment, 45% of the control patients and 27% of the active group had a nonvertebral fracture, but this difference was not statistically significant (p ‫ס‬ 0.2). The total number of fractures was 18 in the 22 control patients and 13 in the active group (relative risk, 0.36; 95% CI, 0.15-0.87; p < 0.05). Conclusion: Intravenous neridronate infusions, administered quarterly, significantly increase BMD and lower the risk of clinical fracture in prepubertal children with OI.

Osteogenesis imperfecta (OI) is a heritable disease of connective tissue, characterized by increased bone fragility. Bisphosphonates currently seems to be the most promising therapy, at least in children. We tested IV neridronate, an amino-bisphosphonate structurally similar to alendronate and pamidronate in adults with OI. Twenty-three men and 23 premenopausal women with OI were randomized to either iv neridronate (100 mg infused intravenously for 30 minutes every 3 months) or no treatment with a ratio of 2 to 1. Control patients were given the same bisphosphonate therapy at the end of the first year. Clinical evaluation included bone densitometry measurements using dual energy X-ray absorptiometry (DXA), fasting serum and urinary biochemistry every 6 months, and radiographs of the spine taken at baseline and after 12 and 24 months of follow-up. Spine and hip bone mineral density rose by 3.0 ؎ 4.6% (SD) and by 4.3 ؎ 3.9%, respectively, within the first 12 months of treatment, whereas small insignificant changes were observed in the control group. During the second year of follow-up, additional 3.91% and 1.49% increases were observed at the spine and hip, respectively. Markers of skeletal turnover significantly fell during neridronate treatment.