Bone Abstracts

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...

Tenofovir disoproxil fumarate (TDF) is a critical component of first-line antiretroviral regimens for HIV worldwide. However, TDF-containing regimens have been associated with decreased bone mineral density and increased fracture risk, which may in part be mediated through secondary elevations in parathyroid hormone (PTH). Prior cross-sectional data suggest vitamin D binding protein (DBP) levels may increase with TDF exposure leading to a functional vitamin D deficiency, which...

Atypical femur fractures (AFF) have been associated with antiresorptive therapy. In a retrospective case-control study, we identified AFF using ASBMR 2013 criteria. Femoral shaft fractures were identified using ICD9 codes. We screened 1479 radiographs. Radiographs were excluded for high-energy trauma, tumor, or periprosthetic fracture. Two radiologists blinded to treatment scored 482 radiographs for AFF features, and jointly adjudicated discrepancies. The required AFF feature,...

Objective: Good oral health is important for well being especially in the elderly. Osteonecrosis of Jaw is rare side effect of bisphosphonates and Denosumab. Patients need adequate dental precautions and appropriate advice from doctors and dentists to reduce the chance of this condition. Aim of the study was to assess the dental health of patients with osteoporotic fractures receiving bisphosphonate or denosumab treatments.Methods: Single person administ...

Adiponectin has recently been shown to influence skeletal metabolism. Over-expression of adiponectin gene suppresses bone resorption and increases trabecular bone mass. Bone marrow stromal cells from adiponectin-null mice had reduced mineralized nodule formation ability compared with wild type mice. Adiponectin, signalling via the adiponectin receptor 1 (AdipoR1) stimulates osteoblast differentiation and inhibits osteoclastogenesis. We have shown that the globular for...

Objectives: In XLH, FGF23-mediated hypophosphatemia leads to defective bone mineralization and rickets. Investigational product KRN23 binds FGF23 and inhibits its activity. The objective of this Phase 2 study was to evaluate the safety and efficacy of KRN23 in 52 children with XLH (ages 5–12 years, ≤Tanner 2).Methods: Patients were randomized to receive KRN23 biweekly (Q2W) or monthly (Q4W) by SC injection. KRN23 dose was titrated (maximum 2 m...

Background: Intravenous (IV) bisphosphonate (BP) is used for treatment of painful vertebral fractures (VF) in children with underlying chronic conditions. BP effect on vertebral height reshaping in this population is however poorly studied.Aims/Objectives: To evaluate the impact of IV BP on vertebral morphometry in children with VF and underlying chronic medical conditions with associated glucocorticoid (GC) therapy.Methods: Retros...

Objectives: Limited data exist on growth parameters in children with hypophosphatasia (HPP), a rare metabolic disease characterized by impaired bone mineralization. We aimed to describe growth characteristics in untreated children with HPP enrolled in the Global HPP Patient Registry.Methods: Children (<18 years old) with a diagnosis of HPP who were not receiving enzyme replacement therapy with asfotase alfa at the time of evaluation were identified f...

Introduction: ENPP1 Deficiency manifests as GACI type 1 in infants, a disorder characterized by extensive arterial calcifications and stenoses, often fatal in utero or in early infancy. Beyond six months, the mortality rate significantly decreases among survivors, who may later develop ARHR2, characterized clinically by short stature, bone deformities and pain. ABCC6 Deficiency also manifests as GACI type 2 in infants and is clinically indistinguishable from GACI type 1. Anima...

Objectives: The objective of this study is to characterize patterns of bone morphology in children with osteogenesis imperfecta (OI), using measurements of the second metacarpal. A secondary objective is to look for impact of bisphosphonate treatment on bone morphology in this population.Methods: This is an IRB-approved retrospective review of 82 de-identified bone age films (AP hand/wrist) for 42 children with OI (17M, 25F). Measurements (Sectra IDS 7 P...