Bone Abstracts

The cathepsin K inhibitor odanacatib (ODN) is a bone formation-sparing inhibitor of osteoclastic resorption activity. This drug is currently under development for the treatment of postmenopausal osteoporosis. To support the bone safety profile of ODN, we evaluated the effects of ODN on trabecular bone hard tissue properties in the estrogen-deficient model of the ovariectomized (OVX) rhesus monkeys. Animals (n=16/group, age 11–22 years) were treated immediately af...

Transforming growth factor (TGF)-β1 is the most abundant growth factor in human bone. Several polymorphisms have been described in the TGF-β1 gene (TGFB1). We have previously shown that individuals with the CC genotype of the T29C polymorphism have higher bone mass at the femoral neck. The T29C polymorphism causes a change from leucine to proline at codon 10, which is located in the hydrophobic α-helical part of the signal peptide....

Background and methods: Pigment epithelium-derived factor (PEDF) is a potent antiangiogenic factor, ubiquitously expressed and secreted in human tissues. Hypertrophic cartilage and osteoblasts express PEDF that binds to type I collagen and glycosaminoglycans in the extracellular matrix. Two rare forms of osteogenesis imperfecta (OI) with intact collagen synthesis are associated with PEDF deficiency. Histological observations revealed excessive osteoid formation and prolonged m...

Peak bone mass is a major determinant of osteoporosis risk and subsequent fragility fractures in older age. There is a wide range of factors influencing peak bone mass, ranging from those acting very early in life, for example in utero and periconception, to those acting through childhood and adolescence into young adulthood. In this presentation I will give an overview of some overarching themes and principles of relevance to peak bone mass, using specific clinical scenarios ...

Objectives: Conventional wisdom suggests that bone is most responsive to physical activity during the growing the years, especially the period just before puberty. Few studies have addressed the entire period of adolescence and even fewer have done so using bone imaging techniques to capture structural outcomes which contribute to bone strength. Using a well-defined cohort (The Iowa Bone Development Study, IBDS), this report examined the magnitude and consistency of the associ...

The relationship between vitamin D status and lean mass accretion in young children is not well understood.Objective: To explore vitamin D status in relation to lean mass outcomes over 12 mo in children 2–8 years.Methods: This was a secondary analysis of trial data (clinicaltrials.gov: NCT02097160, NCT02387892) in Montreal, Canada. Children consumed their normal vitamin D intake for 6 mo (Apr–Oct 2014, n=39) and ...

Survival of chronic diseases in childhood is often achieved utilizing glucocorticoids. However, the survival comes at a cost to the growing skeleton, resulting in impairment in the acquisition of peak bone mass and is the major etiology of secondary osteoporosis in children. We recently found that preosteoclasts secrete platelet derived growth factor type BB (PDGF-BB) to promote angiogenesis and osteogenesis during both modeling and remodeling. As glucocorticoid therapy affect...

Objectives: Early-onset osteoporosis is characterized by low bone mineral density (BMD) and reduced bone strength since childhood or young adulthood. Although several monogenic forms have already been identified, the spectrum of mutations and genes behind this condition remain inadequately characterized. Furthermore, it is not clear whether genetic factors determine susceptibility to bone fractures in children with normal BMD. In order to further explore the genetic background...

Background: Fibroblast growth factor 23 (FGF23) is a circulating phosphaturic hormone that also suppresses renal 1α-hydroxylase activity. In adult patients (pts) plasma FGF23 increases in early stages of chronic kidney disease (CKD), even before serum phosphorus changes. In a study of 984 adult renal transplant pts, higher FGF23 levels were independently associated with increased risk of all-cause mortality and allograft loss during 39 months follow-up2</sup...

Objectives: Asfotase alfa (AA), an enzyme replacement therapy, is the only approved treatment for pediatric-onset hypophosphatasia (HPP). We evaluated the safety profile of AA from the clinical trial program spanning pediatric and adult patients.Methods: Safety data were pooled from 4 open-label, multicenter studies in children aged ≤3 years (study 002/003 [NCT00744042/NCT01205152]; n=11) and ≤5 years (study 010-10 [NCT01176266]; <em...