Bone Abstracts

Bone disease is the most frequent complication in multiple myeloma (MM) resulting in pain, bone fractures, spinal cord compression and hypercalcemia. Within the bone marrow microenvironment (BMM), MM cells interact with bone cells to enhance bone resorption activity and compromise new bone formation mechanism; in turn, BMM provides a survival and drug resistance framework by interaction of MM cells with bone marrow components. Exosomes are important mediators of crosstalk betw...

Objective: The purpose of this study was to determine whether osteogenesis imperfecta (OI) patients entering adulthood should continue with bisphosphonate therapy or would benefit from switching to a RANKL blockade therapy. To address this question, we used a mouse model of type III OI.Methods: Animal studies were performed under IACUC approval. OI (oim/oim) and wild-type (WT) mice were treated from 2–26 weeks with i) saline; ii) alendronat...

Objective: The purpose of this ongoing study was to determine whether osteogenesis imperfecta (OI) patients entering adulthood should continue with bisphosphonate therapy or would benefit from switching to a RANKL blockade therapy. To address this question, we used a mouse model of type-III OI.Methods: Under IACUC-approval, +/+ and oim/oim mice were treated from 2–26 weeks (n=20/treatment/genotype) with either 1) saline 24 weeks; 2...

Tumour necrosis factor receptor-associated factor 6 (TRAF6) plays a key role in osteoclastogenesis through the regulation of RANK/CD40 TRAF6-mediated signaling. Mice deficient in TRAF6 exhibit high bone mass and were protected against inflammation-induced bone loss. Here we describe the effects of a small-molecule 6877002 that has been shown to prevent the binding of TRAF6 to its domain on RANK/CD40 receptor on osteoclast formation in vitro and in vivo and on...

Background: Rickets is a disorder of the growing child arising from impaired mineralisation of the growth plate and osteoid. The most common cause of NR in the UK is thought to be secondary to vitamin D deficiency [VDD; serum 25-hydroxyvitamin D (25OHD) <25 nmol/l], although in some African & South Asian countries dietary calcium deficiency (DCaD) by itself, or together with VDD is an important cause of NR (Ann Trop Paediatr. 2006;26:1–16). Currently, the data on ...

Objectives: Rickets is a disease of growing children with potentially serious short and long-term complications. The United Kingdom (UK) national incidence of Nutritional Rickets(NR) is unknown and thought to be increasing. This study aims to describe the incidence, presentation and clinical management of children with NR in the UK and Republic of Ireland.Methods: Data is being collected prospectively monthly between March 2015 and March 2017 from 3500 p...

Introduction: One third of patients in the long-term heparin therapy show reduction in bone density. We have shown that heparin binds to bone morphogenetic protein 6 (BMP6) and inhibits its osteogenic activity in vitro. Here we explored whether heparin effects BMP6 mediated bone efficacy in vivo.Methods: We have used a mouse model of postmenopausal osteoporosis and tested the effect of heparin on BMP6 therapy and its osteogenic activity...

Prolyl hydroxylase 2 (PHD2) regulates hypoxia-inducible factor α (HIFα) transcription factors and thus, erythropoietin (EPO) production. Under normoxic conditions, HIFα is constantly inactivated through hydroxylation by PHD2. Due to the embryonic lethality of PHD2 knock-out mice, its precise role in erythropoiesis and tissue homeostasis has long remained unknown. Recently, we generated a conditional knock-out (cKO) mouse lacking PHD2 in EPO-producing cells. Thes...

Type 2 diabetes mellitus impairs bone quality and increases fracture risk. We showed that diabetic ZDF rats have low bone mass due to impaired osteoblastogenesis, which can be partially reversed with an intermittent parathyroid hormone 1–84 (PTH) therapy. It remains unclear, why PTH treatment does not fully restore osteoblast (OB) function in diabetic conditions. Here, we tested if high glucose (HG) conditions lead to a partial PTH resistance in osteoblasts. Pre-osteoblas...

Iron overload due to hemochromatosis or chronic blood transfusions has been implicated in the development of osteoporosis. However, the impact of iron overload or iron deficiency on stromal cell functions and the underlying mechanisms are poorly defined. Since the Wnt signaling pathway is a critical regulator of bone remodelling, we aimed to analyse the effects of iron overload and iron deficiency on osteoblast function and further define the role of Wnt signaling in these pro...