Bone Abstracts

Over the years, it has been demonstrated that the ability to maintain body core temperature in older adult’s declines with age. Temperature is a vital physical factor for cell growth and a downshift in core body temperature (<37 °C) might have a direct affect on maintaining bone density or repair fractures. Disruption in any of the cellular processes involved in bone remodelling leads to a net loss of bone mineral density and bone loss. Therefore our study looked...

Ablation of osteosarcoma cells by sublethal hypothermia before radiation may increase sarcoma tissue sensitivity by inducing growth arrest. Normal cells that are not lethally damaged by hypothermia and radiation can undergo DNA repair thus promoting cell survival. Nevertheless, understanding of the response of normal bone forming osteoblast cells towards hypothermia is necessary before administering on osteosarcoma cells. In this study we evaluated the response of short-term m...

Treatment with sclerostin antibody (Scl-Ab) increases bone formation and strength in animal models. Here, we aimed to i) characterize the longer-term effects of Scl-Ab on bone in cynomolgus monkeys (cynos) and ovariectomized (OVX) rats and ii) test whether follow-up treatment with OPG-Fc would maintain the bone mass gains induced by Scl-Ab in OVX rats. In the cynos study, 3 to 5-year-old male cynos were treated for 6 months with weekly SC injections of vehicle (Veh), 3, 10, or...

Loss of the gene encoding the secreted Wnt antagonist sclerostin results in increased bone mass in humans and mice. Administration of antibodies to sclerostin (Scl-Ab) has been shown to increase bone mineral density (BMD) by increasing bone formation and decreasing bone resorption, in both animal studies and human clinical trials. In these studies, the magnitude and rate of increase in bone formation markers, and the rate of increase of BMD, diminishes upon repeat dosing with ...

Osteoporosis and vertebral fractures are recognised complications of ankylosing spondylitis (AS) but the underlying causes are incompletely understood. Osteoprotegerin (OPG) is a decoy receptor for RANK-L and inhibits osteoclastogenesis. We have previously demonstrated that antibodies to OPG (OPG-Ab) are associated with osteoporosis and increased bone turnover in patients with autoimmune diseases. The aim of this study was to determine whether OPG-Abs were detectable in AS pat...

Hyperthyroidism in mice is associated with a low bone mass, an increased bone turnover and high serum levels of sclerostin, a potent Wnt inhibitor. Here, we explored the effects of either reducing bone turnover with bisphosphonates or increasing bone formation with neutralizing sclerostin antibodies (Scl-Ab) on bone mass and estimated strength in hyperthyroid mice.Twelve-week-old C57BL/6 male mice were rendered hyperthyroid by adding L-thy...

Introduction: Osteogenesis imperfecta (OI) is characterized by low bone mass, skeletal fragility and, frequently, short stature. We previously showed in oim/oim mice that sclerostin inhibition increased bone mass, mineral content and strength. Here, we compared the body length and the sizes of long bones, head and vertebrae between oim/oim and wildtype mice and analyzed the effect of sclerostin antibody (Scl-Ab) on these parameters.Materials and methods:...

Previous studies demonstrated a negative influence of the growth- and differentiation factor midkine (MDK) on bone formation during bone remodeling and fracture healing. Additionally, MDK-deficiency protected mice from a loss of trabecular bone mass after ovariectomy (OVX). Therefore, we hypothesized that MDK may also be involved in the pathogenesis of delayed, osteoporotic fracture healing after OVX in mice. Thus, we analyzed the expression of MDK during bone regeneration and...

Thalassemia is a chronic anemia associate with high rates of osteoporosis. To determine how erythropoiesis leads to bone loss in thalassemia, we used the th3/+ thalassemia mouse to study the role of erythropoietin (EPO) and hematopoietic progenitors (HP), since they are both increased in thalassemia.Methods: Bone marrow mesenchymal stem cells (MSCs) cultures and MSC cocultures with various HP from wild type (wt) and th3/+ mice were diff...

Introduction: Bisphosphonate treatment in children with osteogenesis imperfecta reduces bone catabolism and relies on modelling to form new bone. An anabolic treatment, anti-sclerostin antibody (Anti-SOST Ab), is being investigated in clinical trials. We hypothesized that combined treatment may produce superior outcomes in OI.Methods: Female Col1a2 G610C mice and their wild type littermates (WT) were treated from week 5 to week 9 of life with either sali...