Bone Abstracts

In advanced ER+ve breast cancer, the propensity of bone involvement is 85%. Similarly in advanced lung cancer, 30–40% of patients develop bone metastases, and as recent advances in lung cancer therapies improve survival, the number of patients living with bone metastases is expected to increase. At the same time there is a paucity of especially ER+ and osteoblastic animal models available. We present herein the development of four mouse models of breast and lung cancer su...

Introduction: Recessive osteogenesis imperfecta (OI) is caused by mutations in genes encoding proteins involved in post-translational interactions with type I collagen. Types VII–IX OI involve defects in the collagen prolyl 3-hydroxylation complex, which modifies α1(I)Pro986. PPIB encodes CyPB, a complex component with PPIase activity and the major isomerase facilitating collagen folding. We investigated the role of CyPB in collagen post-translational modifications a...

Reduced availability of oxygen, i.e. hypoxia, could occur during disuse, bone development, and fracture. Cartilage tissue is avascular in nature and the microenvironment of cartilage is hypoxic. Hypoxic regulation of gene expression generally involves activation of the hypoxia-inducible factor (HIF) transcription pathway. Receptor activator of nuclear factor-kappaB ligand (RANKL) is an osteoblast/stromal cell derived essential factor for osteoclastogenesis. Hypoxia-induced enh...

Objectives: To elucidate the incidence and risk factors of skeletal toxicity in children with ALL treated with the dexamethasone-based DCOG-ALL9 protocol.Methods: Prospectively, the cumulative incidence of fractures was assessed in 672 patients and compared between different subgroups using the log-rank test. Serial measurements of bone mineral density of the lumbar spine (BMDLS) were performed in 399 ALL patients using dual energy X-ray absor...

Romosozumab is an investigational bone-forming agent that inhibits sclerostin. Recent data demonstrated that it stimulated bone formation, decreased bone resorption, and led to rapid and substantial increases in areal bone mineral density (BMD; McClung, J Bone Miner Res 27 (S1) S8–S9, 2012). In a Phase 1b, randomized, double-blind, placebo-controlled, multiple dose study, we studied the effects of romosozumab administered for 3 months and follow-...

Osteoporotic fractures of the vertebrae are often silent and if left untreated will lead to progressive loss of vertebral body height and significant kyphoscoliosis, with its associated morbidity. However if vertebral fractures (VF) are detected early, treatment with bisphosphonates accelerates healing of prevalent fractures and reduces incident fractures.A survey of members of the British Paediatric and Adolescent Bone Group showed that treatment is sta...

Peak bone mass is a major determinant of osteoporosis risk and subsequent fragility fractures in older age. There is a wide range of factors influencing peak bone mass, ranging from those acting very early in life, for example in utero and periconception, to those acting through childhood and adolescence into young adulthood. In this presentation I will give an overview of some overarching themes and principles of relevance to peak bone mass, using specific clinical scenarios ...

Biographical DetailsNicholas HarveyNicholas Harvey was appointed to a personal chair at the University of Southampton in 2015, and leads, with Professor Cooper and Professor Dennison, an MRC programme focused on the lifecourse epidemiology of bone and joint disease, as part of the MRC Lifecourse Epidemiology Unit. He is working to i) translate epide...

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