Sarcopenia is associated with osteopenia and impaired quality of life in children with genetic intrahepatic cholestatic liver disease.

Background: Sarcopenia occurs in pediatric chronic liver disease, although the prevalence and contributing factors in genetic intrahepatic cholestasis are not well-described. The objective of this study was to measure muscle mass in school-aged children with genetic intrahepatic cholestasis and assess relationships between sarcopenia, clinical variables, and outcomes.

Methods: Estimated skeletal muscle mass (eSMM) was calculated on dual-energy x-ray absorptiometry obtained in a Childhood Liver Disease Research Network study of children with bile acid synthesis disorders(BASD) alpha-1 antitrypsin deficiency (a1ATd), chronic intrahepatic cholestasis (CIC), and Alagille syndrome (ALGS).

Low-Intensity Vibration Protects the Weight-Bearing Skeleton and Suppresses Fracture Incidence in Boys With Duchenne Muscular Dystrophy: A Prospective, Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

The ability of low-intensity vibration (LIV) to combat skeletal decline in Duchenne Muscular Dystrophy (DMD) was evaluated in a randomized controlled trial. Twenty DMD boys were enrolled, all ambulant and treated with glucocorticoids (mean age 7.6, height-adjusted -scores [HAZ] of hip bone mineral density [BMD] -2.

Bone Density in Children With Chronic Liver Disease Correlates With Growth and Cholestasis.

Osteopenia and bone fractures are significant causes of morbidity in children with cholestatic liver disease. Dual-energy X-ray absorptiometry (DXA) analysis was performed in children with intrahepatic cholestatic diseases who were enrolled in the Longitudinal Study of Genetic Causes of Intrahepatic Cholestasis in the Childhood Liver Disease Research Network. DXA was performed on participants aged >5 years (with native liver) diagnosed with bile acid synthetic disorder (BASD), alpha-1 antitrypsin deficiency (A1AT), chronic intrahepatic cholestasis (CIC), and Alagille syndrome (ALGS).

Perfluoroalkyl substances, bone density, and cardio-metabolic risk factors in obese 8-12 year old children: A pilot study.

Background And Objective: Perfluoroalkyl substances (PFASs), including perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), perfluorohexane sulfonic acid (PFHxS), and perfluorononanoic acid (PFNA), have been associated with adverse bone, and metabolic changes in adults. However association of PFASs with bone health in children is understudied. Considering their role as endocrine disruptors, we examined relationships of four PFASs with bone health in children.

Associations between genetic variants and the effect of letrozole and exemestane on bone mass and bone turnover.

Adjuvant therapy for hormone receptor (HR) positive postmenopausal breast cancer patients includes aromatase inhibitors (AI). While both the non-steroidal AI letrozole and the steroidal AI exemestane decrease serum estrogen concentrations, there is evidence that exemestane may be less detrimental to bone. We hypothesized that single nucleotide polymorphisms (SNP) predict effects of AIs on bone turnover.

Accurate body composition measures from whole-body silhouettes.

Purpose: Obesity and its consequences, such as diabetes, are global health issues that burden about 171 × 10(6) adult individuals worldwide. Fat mass index (FMI, kg/m(2)), fat-free mass index (FFMI, kg/m(2)), and percent fat mass may be useful to evaluate under- and overnutrition and muscle development in a clinical or research environment. This proof-of-concept study tested whether frontal whole-body silhouettes could be used to accurately measure body composition parameters using active shape modeling (ASM) techniques.

Long-term velaglucerase alfa treatment in children with Gaucher disease type 1 naïve to enzyme replacement therapy or previously treated with imiglucerase.

Background: Gaucher Disease type 1 (GD1) often manifests in childhood. Early treatment with enzyme replacement therapy (ERT) may prevent disease complications. We report the assessment of velaglucerase alfa ERT in pediatric GD1 patients who participated in a long-term extension study (HGT-GCB-044, ClinicalTrials.

Velaglucerase alfa (VPRIV) enzyme replacement therapy in patients with Gaucher disease: Long-term data from phase III clinical trials.

Type 1 Gaucher disease is an inherited lysosomal enzyme deficiency with variable age of symptom onset. Common presenting signs include thrombocytopenia, anemia, hepatosplenomegaly, bone abnormalities, and, additionally in children, growth failure. Fifty-seven patients aged 3-62 years at the baseline of two phase III trials for velaglucerase alfa treatment were enrolled in the single extension study.

Safety and efficacy results of switch from imiglucerase to velaglucerase alfa treatment in patients with type 1 Gaucher disease.

Gaucher disease (GD) is a lysosomal storage disorder; symptomatic patients with type 1 GD need long-term disease-specific therapy of which the standard of care has been enzyme replacement therapy (ERT). Thirty-eight of 40 patients (aged 9-71 years) clinically stable on ERT with imiglucerase, safely switched to a comparable dose of velaglucerase alfa (units/kg) during TKT034, a 12-month, open-label clinical study, and for 10-50 months in an extension study. The most common adverse events (AEs) judged to be drug-related in the extension were fatigue and bone pain.

The longitudinal effects of physical activity and dietary calcium on bone mass accrual across stages of pubertal development.

Childhood and adolescence are critical periods of bone mineral content (BMC) accrual that may have long-term consequences for osteoporosis in adulthood. Adequate dietary calcium intake and weight-bearing physical activity are important for maximizing BMC accrual. However, the relative effects of physical activity and dietary calcium on BMC accrual throughout the continuum of pubertal development in childhood remains unclear.

The Official Positions of the International Society for Clinical Densitometry: acquisition of dual-energy X-ray absorptiometry body composition and considerations regarding analysis and repeatability of measures.

In preparation for the International Society for Clinical Densitometry Position Development Conference of 2013 in Tampa, Florida, Task Force 2 was created as 1 of 3 task forces in the area of body composition assessment by dual-energy X-ray absorptiometry (DXA). The assignment was to review the literature, summarize the relevant findings, and formulate positions covering (1) accuracy and precision assessment, (2) acquisition of DXA body composition measures in patients, and (3) considerations regarding analysis and repeatability of measures. There were 6 primary questions proposed to the task force by the International Society for Clinical Densitometry board and expert panel.

Risedronate in children with osteogenesis imperfecta: a randomised, double-blind, placebo-controlled trial.

Background: Children with osteogenesis imperfecta are often treated with intravenous bisphosphonates. We aimed to assess the safety and efficacy of risedronate, an orally administered third-generation bisphosphonate, in children with the disease.

Methods: In this multicentre, randomised, parallel, double-blind, placebo-controlled trial, children aged 4-15 years with osteogenesis imperfecta and increased fracture risk were randomly assigned by telephone randomisation system in a 2:1 ratio to receive either daily risedronate (2·5 or 5 mg) or placebo for 1 year.

Effect of odanacatib on bone turnover markers, bone density and geometry of the spine and hip of ovariectomized monkeys: a head-to-head comparison with alendronate.

Odanacatib (ODN) is a selective and reversible Cathepsin K (CatK) inhibitor currently being developed as a once weekly treatment for osteoporosis. Here, effects of ODN compared to alendronate (ALN) on bone turnover, DXA-based areal bone mineral density (aBMD), QCT-based volumetric BMD (vBMD) and geometric parameters were studied in ovariectomized (OVX) rhesus monkeys. Treatment was initiated 10 days after ovariectomy and continued for 20 months.

High-resolution peripheral quantitative computed tomography and finite element analysis of bone strength at the distal radius in ovariectomized adult rhesus monkey demonstrate efficacy of odanacatib and differentiation from alendronate.

Translational evaluation of disease progression and treatment response is critical to the development of therapies for osteoporosis. In this study, longitudinal in-vivo monitoring of odanacatib (ODN) treatment efficacy was compared to alendronate (ALN) in ovariectomized (OVX) non-human primates (NHPs) using high-resolution peripheral computed tomography (HR-pQCT). Treatment effects were evaluated using several determinants of bone strength, density and quality, including volumetric bone mineral density (vBMD), three-dimensional structure, finite element analysis (FEA) estimated peak force and biomechanical properties at the ultradistal (UD) radius at baseline, 3, 6, 9, 12, and 18 months of dosing in three treatment groups: vehicle (VEH), low ODN (2 mg/kg/day, L-ODN), and ALN (30 μg/kg/week).

Risk factors for fractures and avascular osteonecrosis in type 1 Gaucher disease: a study from the International Collaborative Gaucher Group (ICGG) Gaucher Registry.

We hypothesized that overall disease activity or the severity of involvement of individual disease compartments, as measured by clinical and surrogate markers, predict the risk of avascular osteonecrosis (AVN) or fractures in type 1 Gaucher disease (GD1). We applied our risk-set matched case-control method to identify four patient groups within the International Collaborative Gaucher Group (ICGG) Gaucher Registry based on the presence and absence of AVN and fractures. Characteristics of GD1 were examined by comparing the distributions of each risk factor in cases versus matched controls using conditional logistic regression to calculate adjusted odds ratios (OR).

Evaluation of high-resolution peripheral quantitative computed tomography, finite element analysis and biomechanical testing in a pre-clinical model of osteoporosis: a study with odanacatib treatment in the ovariectomized adult rhesus monkey.

This study aimed to validate finite element analysis (FEA) estimation of strength, identify high-resolution peripheral quantitative computed tomography (HR-pQCT) measures correlating with strength, and evaluate the precision of HR-pQCT measurements to longitudinally monitor effects of osteoporosis treatment in ovariectomized (OVX) non-human primates (NHPs). HR-pQCT images were acquired in three groups of NHPs: Intact (n=10), OVX-odanacatib treated (OVX-ODN 30 mg/kg, n=10) and OVX-vehicle treated (OVX-Veh, n=10) at the ultradistal (UD) and distal 1/3 radii and tibia at 12, 16 and 20 months. FEA estimates of bone strength using the Pistoia criterion were validated by ex-vivo mechanical compression (r(2)=0.

Development of quantitative computed-tomography-based strength indicators for the identification of low bone-strength individuals in a clinical environment.

The aim of this study was to develop quantitative computed-tomography (QCT)-based bone-strength indicators that highly correlate with finite-element (FE)-based strength. Transaxial QCT scans were obtained from 36 major, cadaveric, long bones (humerus, radius, femur and tibia) from 4 females and 2 males, 53 to 86 years old. These images were used to construct the FE models and to develop the QCT-based bone strength indicators under every-day, simplified loading conditions.

Revised reference curves for bone mineral content and areal bone mineral density according to age and sex for black and non-black children: results of the bone mineral density in childhood study.

Context: Deficits in bone acquisition during growth may increase fracture risk. Assessment of bone health during childhood requires appropriate reference values relative to age, sex, and population ancestry to identify bone deficits.

Objective: The objective of this study was to provide revised and extended reference curves for bone mineral content (BMC) and areal bone mineral density (aBMD) in children.

Reducing selection bias in case-control studies from rare disease registries.

Background: In clinical research of rare diseases, where small patient numbers and disease heterogeneity limit study design options, registries are a valuable resource for demographic and outcome information. However, in contrast to prospective, randomized clinical trials, the observational design of registries is prone to introduce selection bias and negatively impact the validity of data analyses. The objective of the study was to demonstrate the utility of case-control matching and the risk-set method in order to control bias in data from a rare disease registry.

Optimal monitoring time interval between DXA measures in children.

The monitoring time interval (MTI) is the expected time in years necessary to identify a change between two measures that exceeds the measurement error. Our purpose was to determine MTI values for dual-energy X-ray absorptiometry (DXA) scans in normal healthy children, according to age, sex, and skeletal site. 2014 children were enrolled in the Bone Mineral Density in Childhood Study and had DXA scans of the lumbar spine, total hip, nondominant forearm, and whole body.

Computed-tomography-based finite-element models of long bones can accurately capture strain response to bending and torsion.

Finite element (FE) models of long bones constructed from computed-tomography (CT) data are emerging as an invaluable tool in the field of bone biomechanics. However, the performance of such FE models is highly dependent on the accurate capture of geometry and appropriate assignment of material properties. In this study, a combined numerical-experimental study is performed comparing FE-predicted surface strains with strain-gauge measurements.

Osteopenia in Gaucher disease develops early in life: response to imiglucerase enzyme therapy in children, adolescents and adults.

Background: In Gaucher disease (GD), acid-β-glucosidase (GBA1) gene mutations result in defective glucocerebrosidase and variable combinations of hematological, visceral, and diverse bone disease. Osteopenia is highly prevalent, but its age of onset during the natural course of GD is not known. It is also unclear if the degree of improvement in osteopenia, secondary to imiglucerase enzyme therapy, differs by the age of the patient.

Tracking of bone mass and density during childhood and adolescence.

Context: Whether a child with low bone mineral density (BMD) at one point in time will continue to have low BMD, despite continued growth and maturation, is important clinically. The stability of a characteristic during growth is referred to as "tracking."

Objective: We examined the degree of tracking in bone mineral content (BMC) and BMD during childhood and adolescence and investigated whether tracking varied according to age, sexual maturation, and changes in growth status.

Height adjustment in assessing dual energy x-ray absorptiometry measurements of bone mass and density in children.

Context: In children, bone mineral content (BMC) and bone mineral density (BMD) measurements by dual-energy x-ray absorptiometry (DXA) are affected by height status. No consensus exists on how to adjust BMC or BMD (BMC/BMD) measurements for short or tall stature.

Objective: The aim of this study was to compare various methods to adjust BMC/BMD for height in healthy children.

Image-based strength assessment of bone.

A patient's bone status is commonly assessed by radiologic methods. Although the desired information concentrates on the probability of future fractures, the radiologic density is widely used as a surrogate for bone strength. There have been attempts to develop new parameters that have a closer relationship with bone strength, but the investigators tend to use a linear relationship between measured density and their strength-related parameter.