Bone Abstracts

Osteosarcoma is the most frequent primary bone tumor that develops mainly in young adults. The survival rate at 5 years is below 30% for patients with poor response to treatment or with metastasis.The histones modifications are of critical importance in maintaining the transcription program of both normal and tumor cells. The bromodomain and extra-terminal domain (BET) protein family is an important class of ‘histone reading protein’ capable to...

α2C Evidences demonstrate that sympathetic nervous system (SNS) activation causes osteopenia via β2-adrenoceptor (β2-AR) signaling. In a recent study, we showed that female mice with chronic sympathetic hyperactivity due to double knockout of adrenoceptors that negatively regulate norepinephrine release, α2A-AR and α2C-AR (α2A/α2C-ARKO), present an unexpected phenoty...

Marine cyanobacteria have been recognized as an important source of bioactive compounds. The cytotoxicity on cancer cell lines has been extensively explored and several cyanobacteria metabolites are already described as potential anticancer compounds or are considered useful templates for the design of new anticancer drugs. The majority of compounds have been isolated from filamentous or colonial cyanobacteria that growth in high densities along shores. In contrast, picoplankt...

Strontium ranelate is a promising drug used in the treatment of osteoporosis. This drug has a unique dual effect on bone turnover, simultaneously increasing bone formation by osteoblasts (anabolic effect) and decreasing bone resorption by osteoclasts (antiresorptive effect). The goal of this study was to evaluate: i) anabolic effects of strontium ranelate on the formation of bone-like mineralized matrix in osteoblast cell cultures and ii) changes the drug could cause on the ma...

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 femoral neck fractures (FNF) are one of the most common non-traumatic fractures in elderly people. Frequently the patients with fractures of this localization need surgical treatment and long-term rehabilitation. It’s widely known that FNF in patients with rheumatoid arthritis (RA) occur more often than in the population.Background: To determine the frequency of FNF in patients with RA and to characterize the patients with RA and with FNF at the...