Bone Abstracts

Background: Cardiovascular disease is the leading cause of death in pediatric (ped) and adult ESRD patients. Left ventricular hypertrophy (LVH) is an independent predictor of mortality in ESRD. Besides traditional risk factors, such as high BP & fluid overload, high plasma FGF23 is associated with LVH in adult ESRD patients. Little is known about Kl, the renally produced cofactor of FGF23 for phosphorus (P) homeostasis. We studied ped HD patients for risk factors for LVH, ...

Background: Osteogenesis imperfecta (OI) is a heterogeneous group of disorders characterized by bone fragility. The current classification comprises five forms (OI types I–V) with autosomal dominant inheritance and seven rarer forms (OI types VI–XII) with recessive inheritance. OI type V (MIM 610967) has distinguishing radiological features, such as propensity to hyperplastic callus formation, calcification of the forearm interosseous membrane, radial-head dislocatio...

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Relatively little is known about immediate consequences of continuing vs interrupting long-term bisphosphonate treatment. This report describes changes in bone turnover and BMD in a 1-year, dose-finding trial of the calcium-sensing receptor antagonist MK-5442 in postmenopausal, BP-treated women, randomized to continued alendronate 70 mg weekly, switch to placebo, or switch to MK-5442. Recruited women (n=526) had taken alendronate for ≥12 months and an oral BP fo...

Fibroblast growth factor-23 (FGF23) is a bone derived phosphate-regulating hormone which is elevated in hypophosphataemic rickets. Recent findings demonstrate iron deficiency as a potential mediator of FGF23 expression and murine studies have shown in utero effects of maternal iron deficiency leading to increased FGF23 concentration and disordered bone development (Clinkenbeard. JBMR 2013). Children with rickets in rural Gambia, West Africa, have high prevalences of i...

Objectives: Murine studies have shown that iron deficiency during pregnancy can cause abnormal phosphate and bone metabolism in offspring by elevating concentrations of fibroblast growth factor-23 (FGF23). FGF23 exists in plasma as an intact phosphate- and vitamin D-regulating hormone and its C-terminal fragment, a cleavage product that possibly antagonises the intact hormone. These findings are pertinent to low-income countries, where the prevalence of iron deficiency in preg...

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 ...

Cancer-associated muscle weakness is an important paraneoplastic syndrome for which there is currently no treatment. Human breast cancer bone metastases (MDA-MB-231 cells in immune deficient mice) induce extensive bone destruction, leading to the release of TGF-β from the bone matrix. We have previously shown that bone-derived TGF-β is responsible for muscle weakness in this model. Mechanistically, TGF-β signaling increases the expression of NADPH oxidase 4 (Nox...

Effects of whole bone scaling on isolated osteoblast behaviours are unknown. Exhibiting a huge range in size, inbred canines are an ideal species to determine such relationships. We have therefore undertaken initial studies in both male and female red foxes (Vulpes vulpes), the most abundant and accessible wild canid member in the United Kingdom.Femoral heads were removed from five fresh red fox cadavers (see details on table) and bone fragments...

Hip osteoarthritis is a cause of significant morbidity to people and their canine companions. Medical management is frequently insufficient, leading to surgery to relieve pain and regain mobility. Hip replacements are not without potential complications, including loosening and infection. Currently, there is a focus on uncemented implants to decrease these problems, however these rely on the biology of the femur for osseointegration and long-term stability. It has been previou...