Bone Abstracts

Osteogenesis Imperfecta (OI) is a rare congenital disorder of bone fragility. Majority of OI cases are caused by loss of function or missense pathogenic variants in the COL1A1/2 genes. In addition to fractures, patients suffer from different, mainly long bone, skeletal deformities. OI patients might develop chest deformities (pectus carinatum (PC) or excavatum (PE)) of different severity, which can tend to formation of cardiopulmonary complications. The main aim of current stu...

Objectives: Fibroblast growth factor 23 (FGF23) is a bone-derived phosphaturic hormone. The main target organ is the kidney, where FGF23 suppresses renal phosphate reabsorption and vitamin D synthesis. It also stimulates calcium reabsorption in the kidney. FGF23 secretion is stimulated by 1,25(OH)2D and by increased extracellular phosphate concentration, thus forming a feedback loop between kidney and bone. The bioactive intact FGF23 contains 251 amino acids and is glycosylate...

Objectives: Hypophosphatasia (HPP) is a rare metabolic disease caused by loss-of-function mutation(s) in the gene encoding tissue-nonspecific alkaline phosphatase (TNSALP). HPP in infants is characterized by poor skeletal mineralization, respiratory compromise, and a high risk of mortality. We previously reported improved mineralization and respiratory function in 15 patients enrolled in this second study of asfotase alfa, a bone-targeted recombinant human TNSALP, in infants a...

Aims: Using an extensive bioinformatic approach we identified integrin α5 subunit as a novel potential target to treat bone dissemination from breast cancer. Aim of this study is to confirm the value of this target.Methods: Integrin α5 mRNA expression levels were quantified by qRT-PCR, using radically resected primary tumors of 427 breast cancer patients. α5 expression at protein level by IHC on primary tumor was correlated, in an addition...

Background: Rickets is a disorder of the growing child arising from impaired mineralisation of the growth plate and osteoid. The most common cause of NR in the UK is thought to be secondary to vitamin D deficiency [VDD; serum 25-hydroxyvitamin D (25OHD) <25 nmol/l], although in some African & South Asian countries dietary calcium deficiency (DCaD) by itself, or together with VDD is an important cause of NR (Ann Trop Paediatr. 2006;26:1–16). Currently, the data on ...

Objective: We evaluated the long-term efficacy of burosumab, a monoclonal antibody against FGF23, in a Phase 2 Study (NCT02163577) in children with XLH.Methods: Fifty-two children with XLH (5-12 years-old, Tanner ≤ 2) were randomized 1:1 to receive subcutaneous burosumab Q2W or Q4W for 64 weeks. Doses were titrated up to 2 mg/kg/dose targeting serum phosphorus levels within 1.1–1.6 mmol/l. All subjects entered the long-term extension at Week 6...

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...

Bone turnover markers (BTMs) are particularly useful in the early monitoring of the effectiveness of anabolic and antiresorptive therapy in osteoporosis and may help in the assessment of treatment compliance. How and when BTM levels change under antiresorptive or anabolic drugs is a key factor in assessing response to therapy. Thus, changes in BTM levels depend on the dose of the drug and the route of administration, and particularly on the mechanism of action. In this sense, ...

Screening gene function in vivo is a powerful approach to discover novel drug targets in the human genome (Nat Rev Drug Discov 2 38–51, 2003). We present data for 3776 distinct gene knockout (KO) mouse lines with viable adult homozygous mice generated using both gene-trapping and homologous recombination technologies. Bone mass was determined from PIXImus DEXA scans of male and female mice at 14 weeks of age and by microCT analyses of bones from ...

The relationship between bone formation and blood flow is unclear. Recently, PTH was reported to activate production of nitric oxide (NO), a potent vasorelaxing agent, in endothelial cells and we and others have confirmed a strong vasorelaxing action of PTH in vivo in the mouse. Here, we tested the hypothesis that a potent NO synthase inhibitor (L-NAME: NG-nitro-L-arginine methyl ester) may alter the effect of intermittent PTH (iPTH) on b...