Bone Abstracts

Many disorders cause osteosclerosis, and many exclusively affect adults. Pediatricians are likely to encounter those that are Mendelian diseases, with most still classified as ‘dysplasias’ although now understood at the gene level. Thus, there is promise for defining their molecular and biochemical pathogeneses, and for developing targeted medical treatments. Sclerosing bone dysplasias too have become the ‘turf’ of the metabolic bone disease specialist. How...

Biographical DetailsMichael P Whyte is Professor of Medicine, Pediatrics, and Genetics at the Washington University School of Medicine, a staff member of Barnes-Jewish Hospital and St. Louis Children’s Hospital, and Medical-Scientific Director at the Center for Metabolic Bone Disease and Molecular Research, Shriners Hospital for Children in St. Louis, Missouri, USA.<p class="abst...

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Hypophosphatasia (HPP) is the rare inherited metabolic disease caused by loss-of-function mutations in the tissue-nonspecific alkaline phosphatase (TNSALP) gene. TNSALP deficiency leads to extracellular excess of inorganic pyrophosphate, a bone mineralization inhibitor. Here, we report the validity and reproducibility of a novel scale to quantify HPP-specific radiographic changes in pediatric patients.The Radiographic Global Impression of Change (RGI-C) ...

Background: Hypophosphatasia (HPP) results from inactivating mutation(s) in the gene for tissue non-specific alkaline phosphatase (TNSALP). Substantial improvement has been reported in skeletal mineralization and physical function in patients (pts) with life-threatening perinatal and infantile HPP treated for 48 weaks with asfotase alfa, a bone-targeted recombinant human TNSALP.Objective: To evaluate long-term efficacy and tolerability of asfotase alfa i...

Objective: Children with hypophosphatasia (HPP) treated with asfotase alfa in a Phase 2 study (NCT00952484) and its open-label extension (NCT01203826) experienced significant improvements in skeletal mineralization and physical function that were sustained through 5 years of treatment (1). Herein, we report data from these studies with a maximum of 7 years of treatment.Methods: Children with HPP aged 6–12 years at baseline received asfotase alfa (3 ...

Objective: To evaluate safety and efficacy after 5 years of treatment with asfotase alfa in adolescents and adults with hypophosphatasia (HPP) in a Phase 2, open-label, randomized, dose-ranging study (NCT01163149).Methods: Treatment with subcutaneous asfotase alfa 0.3 or 0.5 mg/kg per d was compared with no treatment (control) for 6 months in patients aged 13–66 years. After 6 months, all patients (treatment and control groups) received active treat...

Objective: We constructed height growth curves for children with XLH from birth to early adolescence, a majority of whom received conventional therapy consisting of multiple daily doses of oral phosphate and active vitamin D.Methods: Growth data from four clinical studies were pooled to construct the growth curves. UX023-CL002 was an observational, retrospective chart review of 103 children with XLH, 1–14 years of age. Pre-treatment data were collec...

Objectives: Asfotase alfa (AA), an enzyme replacement therapy, is the only approved medical treatment for pediatric-onset hypophosphatasia (HPP), which is caused by deficient tissue-nonspecific alkaline phosphatase activity. We detail the long-term efficacy of AA observed from the pediatric clinical trial program.Methods: Efficacy data collected to study completion were pooled from 3 open-label, multicenter investigations of children who manifested HPP s...

Background: Hypophosphatasia (HPP) is caused by inactivating mutation(s) in the gene for tissue non-specific alkaline phosphatase. Extracellular accumulation of inorganic pyrophosphate can lead to profound hypomineralization resulting in limb and chest deformity, respiratory complications and vitamin B6-dependent seizures in the severe forms of HPP. The natural history of HPP is poorly understood, but the perinatal and infantile forms are often considered lethal.<p class="...