Bone Abstracts

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...

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Objective: Children with hypophosphatasia (HPP) treated with asfotase alfa in a Phase 2 study (NCT00952484) and its open-label extension (NCT01203826) experienced significant improvements in skeletal mineralization and physical function that were sustained through 5 years of treatment (1). Herein, we report data from these studies with a maximum of 7 years of treatment.Methods: Children with HPP aged 6–12 years at baseline received asfotase alfa (3 ...

The endocannabinoid system has important effects on bone mass and bone turnover. Mice with targeted inactivation of type 1 (CB1) and type 2 (CB2) cannabinoid receptors develop osteoporosis with increasing age raising the possibility that cannabinoid receptor agonists might protect against age-related bone loss. Since cannabis is the most widely used illegal drug and its main psychotropic component -Δ9-tetrahydrocannabinol (THC)- is an agonist at CB1 and CB2 receptors, we ...

Objectives: To define the role of bone morphogenetic proteins (BMP) in human osteochondromas. The expression of bone morphogenetic proteins and their corresponding receptors has not been clarified in osteochondromas. We determined immunohistochemically the localization and distribution of bone morphogenetic proteins 2, 4, 6 and 7, bone morphogenetic protein receptor types 1A, 1B and 2 and the functional effectors phosphorylated Smad proteins 1, 5 and 8 in the cartilaginous cap...

Objectives: Intravenous bisphosphonates have been used in children for various primary and secondary bone fragility disorders for three decades but beyond osteogenesis imperfecta, there is very limited information published in relation to outcomes. We report the experience at the Royal Children’s Hospital (RCH), Melbourne using Zoledronic acid (ZA), describing outcomes based on the underlying condition for which treatment was given, with the aim of informing future protoc...

Objectives: The primary objective of this project was to determine the nature and timing of perceived early adverse effects associated with bisphosphonate therapy. Additional information was sought on how this affected the child and family, to determine if changes should be made to local guidelines.Methods: A Smartphone-based text message survey was sent to parents of patients receiving intravenous bisphosphonate therapy for primary and secondary osteopo...

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Osteocytes differentiate from osteoblasts, are embedded in mineralised matrix and are critical regulators of bone remodelling. In vitro osteocyte models are limited to cell lines in monolayer, which do not represent their 3D environment in vivo. We have shown that osteoblasts in 3D gels differentiate along the osteocytic pathway. Since IGF1 regulates osteoblasts, and is involved in osteocyte response to mechanical loading, we hypothesised that IGF1 modulates ...

Introduction: Nitrogen-containing bisphosphonates (N-BPs) can inhibit the differentiation and function of osteoclasts derived from Peripheral Blood Mononuclear cells (PBMCs) in a dose-dependent manner. MUTZ-3 cells are a potentially useful human cell line for studying osteoclast differentiation. The aim of this study was to elucidate the action of N-BPs on MUTZ-3 cells.Methods: Human PBMCs and MUTZ-3 cells were cultured in α-MEM supplemented with he...