Bone Abstracts

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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...

Introduction: Standard clinical treatments for postmenopausal osteoporosis utilize resorption-inhibiting drugs such as bisphosphonates, which selectively bind to bone mineral but also suppress bone formation over time. Prostaglandin E2 (PGE2) has bone-anabolic effects in vivo, but its clinical utility is hindered by side effects upon systemic administration. Since PGE2 acts on bone via the EP4 receptor, our approach utilizes a specific...

Children with chronic medical conditions are at increased risk for bone fragility from multiple mechanisms, related both to the underlying condition and its treatment, in particular glucocorticoids. The differential effects of the underlying medical disease on bone micro-architecture have not been well elucidated.Objectives: To describe the bone micro-architectural characteristics in children with rheumatic and oncological disorders treated with glucocor...

Osteoporosis is an age related disease characterised by a progressive decrease of bone mineral density and loss of bone quality. Twin studies show that genetic component contributes up to 85% of the BMD variability of population. Surprisingly little variability of BMD can be explained by genetic polymorphisms (~2.9%). This highlights the complex genetic architecture and suggests that many other molecular processes and genes have to be involved. Our previous research showed tha...

Introduction: Mortality after hip fracture is increased. However, only a few studies have explored for predictors beyond gender and age. Thus our aim was to study risk factors associated with increased mortality in hip fracture patients.Methods: Hip fracture patients (>50 years) admitted to a county hospital in 2004–2005 were consecutively invited for assessment at the hospital osteoporosis centre. A broad spectre of data was collected. Standard...

ASARM peptide (acidic, serine- and aspartate-rich motif) and osteopontin (OPN) fragments accumulate in X-linked hypophosphatemia patients and/or in the Hyp mouse model and, when phosphorylated, potently inhibit mineralization in osteoblast cultures. To investigate this inhibition, we modeled the binding to hydroxyapatite of the human OPN-ASARM peptide (DDSHQSDESHHSDESDEL) using RosettaSurface computational simulations. Peptide binding to hydroxyapatite atomic planes constructe...

Introduction and objective: Despite recent improvements in therapeutic management of osteosarcoma, ongoing challenges in improving the response to chemotherapy warrants the development of new strategies to improve overall patient survival. Among new therapeutic approaches, heat shock protein (HSP) 90 is a molecular chaperone involved in the maturation and stability of various oncogenic proteins leading to tumor cells survival. In this study, we assessed the in vitro a...

Introduction: Prostaglandin E2 has bone-anabolic effects through EP4 receptor but its clinical utility is hindered by gastrointestinal side effects. To avoid these side effects, EP4 agonists (EP4a) were covalently linked to the bisphosphonate alendronate (ALN) to create two ALN-EP4a conjugate drugs, C1 and C2. When administered systemically, C1 and C2 will be target delivered to bone through ALN, where local hydrolytic enzymes liberate EP4a from ALN to exert bone an...

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