Bone Abstracts

Activin is a known physiologic regulator of bone metabolism. Ovariectomy-induced osteopenia has been shown to be attenuated by injection of the activin type IIA decoy receptor (ActRIIA-Fc). However, immobilization-induced osteopenia is driven by different pathways than ovariectomy-induced osteopenia, and the role of activin in immobilization-induced osteopenia has not yet been elucidated.The purpose of the study was to investigate the possible attenuatio...

Extreme high bone mass (HBM) may be monogenic (e.g. LRP5 mutations) or polygenic, due to variants in the same genes determining bone mineral density (BMD) as found in the general population. We aimed to determine how variation in established BMD loci, in different functional pathways, explains the HBM phenotype.241 unexplained HBM cases (lumbar spine(LS)1+total hip(TH) Z-scores≥+4.4) were recruited from 15 UK centres, by screening...

Biomechanical strength testing of bones, considered a key component in bone quality assessment, is a critical end-point in the evaluation of safety and efficacy of test compounds in preclinical studies. Bones are usually preserved frozen and tested within a few months following harvesting. They can also be stored for longer periods and only tested when additional information is required. The objective of this study was to evaluate if differences in biomechanics data between di...

Periosteum contains mesenchymal progenitors and is essential for fracture healing. Signaling mechanisms governing periosteal reaction to injury remain largely unidentified. We previously investigated how PI3 kinase signaling affects the skeletal system using CblYF/YF knock-in (YF) mice wherein PI3K signaling is perturbed by abolition of interaction between Cbl, an E3 ubiquitin-ligase/adaptor protein, and p85 subunit of PI3K. YF mice displayed increased bone volume u...

It is unclear as to whether western dwelling South Asian (SA) postmenopausal women have a different fracture risk to that of the native Caucasian (C) population. Moreover, the WHO Fracture Risk Assessment Tool (FRAX) has not been used previously to compare predicted risk of fractures in western dwelling South Asian women with same-age Caucasian women. This analysis used data from n=35 SA [mean (S.D.) age=59 (6) years] and n=136 C [mean (...

Background: Severe vitamin D deficiency (VDD), is a common disorder, which has complications including rickets, hypocalcaemia, hypotonia, delayed development and cardiomyopathy. Although nutritional rickets associated craniosynostosis has been reported, there is little awareness of this or knowledge about its clinical course or severity. We present five cases of late onset craniosynostosis in association with nutritional rickets.Clinical presentation: Th...

Objectives: Burosumab, a monoclonal antibody that therapeutically targets the underlying elevated levels of fibroblast growth factor 23 (FGF23) in X-linked hypophosphatemia (XLH), is now available to children out of trial conditions. Our objective was to describe the effect of burosumab on quality of life, functionality and pain in a clinical setting.Methods: Questionnaire tools were completed at baseline, 6 and 9 months for 9 children with XLH starting ...

Background: Inherited forms of rickets are metabolic bone diseases developing as a result of inadequate mineralization of a growing bone due to disruption of calcium, phosphorus and/or vitamin D metabolism. Diverse phenotypic presentation and aetiology of these disorders pose difficulties for the diagnosis and management.Objective and hypotheses: The aim of this study was to perform molecular diagnostics and clinically characterize 137 patients with here...

Objective: Osteogenesis imperfecta is characterized by hereditary skeletal fragility. Bisphosphonates are the first line medical treatment in moderate and severe OI types III/IV. There is no consensus regarding treatment beginning and treatment regimen in the first years. Objective of the presented project was the evaluation of the therapeutic effect of 1 year of bisphosphonate treatment (BP; neridronate i.v. 2 mg/kg body weight every 3 months) on vertebral shape and mobility ...

Hypophosphatasia is a recessively inherited disorder with a wide phenotypic manifestation ranging from lethality in neonates to asymptomatic in adults. The severity of the phenotype is largely determined by the nature of the ALPL mutations. We describe a previously asymptomatic adult whose phenotype dramatically changed after he developed renal failure. A 50-year-old man was diagnosed with IgA nephropathy. At age 52 (eGFR 50 ml/min) he suffered his first metatarsal fr...