Bone Abstracts

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...

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...

Destructive bone lesions due to osteolytic bone disease (OBD) are a major cause of morbidity and mortality in multiple myeloma (MM) patients and the development of new therapeutic strategies is of great interest. In this study, we assessed the effect of SRC inhibition with saracatinib (AZD0530, AstraZeneca) on the development of MM and its associated OBD. We first determined SRC family kinase expression in the MM microenvironment and found that myeloma cells express SRC at low...

Breast cancer cells that escape primary tumors disseminate to bone with high affinity at late-stage disease. Circulating breast tumor cells that invade the bone marrow (BM) express sets of deregulated genes and/or microRNAs (miRNAs) that facilitate their bone tropism and enhance engraftment of disseminated tumor cell (DTC) in BM which may subsequently induce osteolytic lesions. MiRNA transcriptomic profiling of the human breast cancer DTC cell line, BC-M1, and of the osteotrop...

Objectives: XLH features renal phosphate (Pi) wasting, hypophosphatemia, rickets, and skeletal deformities from elevated circulating levels of fibroblast growth factor 23 (FGF23). KRN23, an investigational fully human monoclonal antibody, binds FGF23 and inhibits its action. Our Phase 2 study of KRN23 in XLH children (ages 5–12 years) is demonstrating improvements in serum Pi and rickets. Here we present our Phase 2 trial evaluating the efficacy and safety of KRN23 in you...

The pathogenesis of skeletal fragility in diabetes mellitus is poorly defined and efficient therapies are limited. Zucker diabetic fatty (ZDF) rats with type 2 diabetes mellitus display low bone mass and delayed bone defect healing. We tested whether intermittent treatment with human parathyroid hormone 1–84 (PTH) increases bone mass and bone defect regeneration in diabetic rats.A subcritical gap defect was created at the femur of 10 weeks old diabe...

Although bone morphogenetic protein 6 (BMP6) is known for its ability to induce growth of bone and cartilage, recent studies identified BMP6 as a key endogenous regulator of hepcidin expression and iron metabolism. Here, we examined BMP6 presence in the serum and investigated whether circulating levels of BMP6 may reflect body iron status. First, we showed by liquid chromatography–mass spectrometry (LC–MS) and western blotting that BMP6 is present in the circulation ...

In light of prolonged life expectancy, the need for biomaterials that govern bone regeneration increases. Improved bone regeneration and osseointegration can be achieved by funtionalizing implant materials. The extracellular matrix (ECM) affects differentiation of bone cells and is critical for bone regeneration. Here we assessed the role of the natural occurring bone ECM glycosaminoglycans (GAGs) hyaluronan (HA) and chondroitin sulfate (CS), and their sulfated derivatives, on...

Osteoprotegerin gene (OPG) is an important candidate gene of osteoporosis. Association of the OPG polymorphisms and bone mineral density (BMD) have been studied by several research groups, however results are not uniform.The aim of this study was to determine if two polymorphisms in the OPG gene influence bone turnover markers and bone mineral density (BMD) in postmenopausal women and elderly men. A total of 135 patients, aged 41–87 years, were incl...

Diabetes mellitus results in increased skeletal fragility through reduced bone mineral density and altered collagen structure. How these changes affect bone mechanics at the tissue level remains largely unclear. Anti-osteoporosis medications improve bone mass, but whether they can fully restore tissue strength in diabetic bone, where collagen quality is compromised, has not been fully elucidated. The objective of this study was to determine the effect of type 2 diabetes mellit...