Bone Abstracts

Background: We identified a family with early onset X-linked osteoporosis and fracturesMethods: We performed whole exome sequencing of the X chromosome in three affected members. After discovering a putative pathogenic variant we performed Sanger sequencing of all exons of this gene in other members of this family and in 95 unrelated men suspected of OI type I without COL1A1/2 mutations. We also genotyped a SNP in this gene (minor allele frequency 0.02) ...

It has been established that disturbances of intracellular signaling pathways strongly contribute to the oncologic process. Indeed, phosphatidylinositol-3-kinase (PI3K) became a key target in cancer therapy, due to its high frequency of mutation and/or gain of function of its catalytic subunits in cancer cells. In this context, we investigated the in vitro and in vivo effects of a new PI3Kα inhibitor, BYL719 (Novartis Pharma), on bone cells and its thera...

Osteosarcoma is the most common primary malignant bone tumor, characterized by osteoid production and/or osteolytic lesions of bone. Despite recent improvements in chemotherapy and surgery, the problem of non-response to chemotherapy remains and constitutes a poor prognosis parameter. Consequently new therapeutic strategies aim to improve the overall rate of survival. The present work investigated the therapeutic interest of a dual phosphatidylinositol-3-kinase (PI3K)/mammalia...

Objectives: Osteopenia is a complication of childhood cancer treatment but it is unknown to which extend this occurs in adult survivors, and which subgroups are at risk. We examined bone mineral density (BMD) and assed the relative importance of potential determinants of low BMD in very long-term adult survivors of childhood cancer.Methods: The single-center cohort study included 410 adult CCSs (median age at diagnosis: 6.6 years (range: 0–17 years)...

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Osteoporotic fractures are very common and represent an enormous unmet medical need. Our group has previously reported that addition of rTNF to the fracture site promotes fracture healing in C57/BL6 mice (Glass et al. PNAS 2011). Using a murine fracture model of endochondral healing, we observed that local addition of rTNF only accelerates fracture repair if administered within the first 24 h following injury. The optimal therapeutic dose is 1 ng. TNF is firs...

Objective: The physis, or growth plate, is comprised of precisely organized chondrocytes that confer longitudinal growth of the bone. Multiple signaling pathways cooperate to regulate growth through their control of chondrocyte shape, polarity, proliferation, and differentiation.1,2 Disruption of these cellular events result in physeal defects, skeletal deformities, and abnormal limb growth. Loss of function mutations in Smad4, a common intracellular effector of all...

Metatropic dysplasia (MD) was first described by Maroteaux et al. in 1966. Its name was derived from the Greek word metatropos which means ‘changing pattern’ because individuals with this diagnosis begin life with a short-limbed dysplasia and a long trunk with narrow chest, and over time their dysplasia becomes short-trunked due to progressive kyphoscoliosis1. It is now recognized that MD is caused by gain-of-function mutations in transie...

Osteoporosis is a chronic disease with a high prevalence in older adults. There is evidence that statins have some beneficial effects on bone metabolism. Although the trial reports are ambiguous, it is now accepted that statins block the osteoclast differentiation inhibiting to some extent bone resorption. Our aim was to evaluate the effects of a statin in an animal model, which was induced to osteoporosis by glucocorticoids and then treated with atorvastatin. The experimental...

Aim: Magnetic Resonance guided Focused Ultrasound Surgery (MRgFUS) is an invasive treatment able to control local disease and pain of bone tumors. Unfortunately, there is not any scientific evidence of the biological effect of MRgFUS treatment on tumor cells, especially in lower dose region, where tissues are only warmed to sub-lethal temperatures. Here we investigate the effect of in vitro MRgFUS treatment, at different levels of acoustic energy (200–630 J), on ...