Bone Abstracts

Biographical DetailsDr Madhusmita Misra is a full Professor of Pediatrics at Harvard Medical School and a Pediatric Endocrinologist at Massachusetts General Hospital in Boston, Massachusetts. She directs the fellowship training program in Pediatric Endocrinology at Massachusetts General Hospital, and has a Masters in Public Health from the Harvard School of Public Health. Dr M Misra’...

Objective: To evaluate safety and efficacy after 5 years of treatment with asfotase alfa in adolescents and adults with hypophosphatasia (HPP) in a Phase 2, open-label, randomized, dose-ranging study (NCT01163149).Methods: Treatment with subcutaneous asfotase alfa 0.3 or 0.5 mg/kg per d was compared with no treatment (control) for 6 months in patients aged 13–66 years. After 6 months, all patients (treatment and control groups) received active treat...

Screening gene function in vivo is a powerful approach to discover novel drug targets in the human genome (Nat Rev Drug Discov 2 38–51, 2003). We present data for 3776 distinct gene knockout (KO) mouse lines with viable adult homozygous mice generated using both gene-trapping and homologous recombination technologies. Bone mass was determined from PIXImus DEXA scans of male and female mice at 14 weeks of age and by microCT analyses of bones from ...

Glucocorticoids (GC) are effective drugs in the treatment of inflammatory diseases, including various forms of arthritis. However, their use is limited by negative effects on bone mass and strength, resulting in increased osteoporotic fractures. Conditional knockout mice demonstrated that the GR in osteoblasts is essential for GC-dependent bone loss. Recent studies show that GC profoundly inhibit Wnt signaling by stimulating the expression of Wnt antagonists such as dickkopf-1...

Mineralized tissues like bone, articular calcified cartilage or mineralized turkey leg tendon (MTLT) are build by a composite of hydroxyapatite nano-particles and organic matrix. In bone and MTLT the matrix is formed by collagen type-I, but in contrast to bone in MTLT the collagen is uniaxial orientated, while in cartilage the matrix consists of collagen type-II and proteoglycans.Composition/orientation differences were investigated by a new scanning aco...

Bone is a tough composite material, comprised of a compliant collageneous matrix, brittle apatite mineral crystals and a suite of non-collageneous proteins (NCPs). Bone material properties depend on these components, and their interactions at the mineral-collagen interface. ‘Bone mineral density’ (BMD), a parameter used to predict fracture risk, is routinely quantified by DEXA. Previous studies used ex vivo emu tibiae as a model to test the effect of organic...

Adaptive responses of the skeleton to loading changes architecture and physical properties in order to optimise strength for function. However, bone is subjected to many local and circulating osteotropic factors, most acting on G-protein coupled receptors. Receptor activity modifying protein-3 is a single trans-membrane domain receptor accessory protein, which aids in trafficking of calcitonin and calcitonin-like receptors to the cell surface and changes ligand selectivity. As...

An IgM monoclonal gammopathy (MGUS) is often the first sign of a lymphomonocytic B-lymphoma (Waldenström macroglobulinemia-WD). Osteolytic lesions can occur in B cell malignancies (WD, hairy cell leukemia, LLC\..) but are less frequent than in myeloma. In addition, bone remodeling in WD is poorly understood. However, an osteoporosis is often observed in MGUS patients. We studied a series of bone biopsies performed in patients with an IgM gammopathy by histomorphometry, mi...

Proton pump inhibitors (PPIs) are a class of drugs particularly used in gastric disorders. They promote a decrease on gastric acid secretion by inhibiting the H+/K+ ATPases. Osteoclasts are cells specialized in bone resorption by H+ translocation to the bone surface. Thus, PPIs might be regarded as potential tools to modulate osteoclast resorption activity, particularly in conditions that are associated with a hyperactivation of osteoclasts, li...

Hydroxyapatite (HA) has been widely used as a biocompatible ceramic in many areas of medicine, mainly for contact with bone tissue, due to its resemblance to mineral bone. Owing to the nanofeatures of bone tissue, new nano-HA based materials are among the most promising challenges in bioactive ceramics. Recently, it was observed that fluoroquinolones have the ability to interfere with osteoclastogenesis, in standard polystyrene cell culture plates. The aim of this work is to a...