Bone Abstracts

Objectives: To assess the safety, tolerability and pharmacokinetic (PK) profile of single and multiple doses of TA-46 administered subcutaneously to healthy volunteers.Methods: This was a double-blind, randomized, placebo-controlled trial in a total of 72 subjects. Cohorts of 8 subjects were randomised to receive either TA-46 or placebo in a 3:1 ratio in single ascending dose (SAD) and multiple ascending dose (MAD) cohorts. SAD doses were 0.3, 1, 3, 10 a...

Objectives: To compare and contrast the natural history of osteoporosis and response to zoledronate in children and adolescents with Duchene muscular dystrophy (DMD), spinal muscular atrophy (SMA) or other congenital muscular dystrophies (CMD).Methods: A retrospective medical record review of fracture history, treatment and bone mineral densitometry of children managed at a tertiary centre in Sydney over the last 6 years.Results: A...

Introduction: Achondroplasia, the commonest skeletal dysplasia, is caused by specific variant(s) in the fibroblast growth factor receptor 3 (FGFR3) gene that cause abnormal spine, skull and limb bone growth. Surgical indications for foramen magnum stenosis in this population vary widely in the literature.Methods: We performed a retrospective analysis of patients with achondroplasia aged >20 years (n=33) in our regional skeletal dysplasia cli...

Hip development is influenced by mechanical loading during fetal movement by joint and reaction forces equivalent to several times bodyweight. These forces increase with fetal size and gestation length, and are lower in oligohydramnios and breech presentation which are both risk factors for developmental hip disorders. However, associations between indicators of prenatal mechanical loading and hip shape in later life remain unexplored. We therefore examined associations betwee...

Objectives: To investigate the impact of Type 1 Diabetes Mellitus (T1DM) on cortical and trabecular microarchitecture, and bone strength in adolescents; using High Resolution peripheral Quantitative Computed Tomography (HRpQCT) and microfinite element analysis. To our knowledge, this is the first study in children, assessing the impact of T1DM on skeletal microstructure and strength using HRpQCT.Methods: We recruited 22 patients aged 12–16 years wit...

Objective: The potential for clinical trials to impact patient care may be limited if the outcomes reported vary by trial and lack direct relevance to patients. We aimed to systematically assess the scope and consistency of outcomes reported in randomised trials of interventions for children with osteogenesis imperfecta.Methods: We systematically searched for all published and unpublished randomised trials of interventions for children with osteogenesis ...

A randomized, placebo-controlled phase 2 study evaluated the safety and efficacy of BA058, an analog of hPTHrP(1–34), in postmenopausal women with severe osteoporosis. 221 patients were randomized to received BA058 20, 40, and 80 μg, placebo or teriparatide (TP) 20 μg, by daily s.c. injection. 184 (83%) patients completed an initial 24 weeks of treatment. The mean percent change in lumbar spine BMD at 24 weeks was 1.6% with placebo, 6.7% with BA058 80 μg, a...

Denosumab treatment is associated with low fracture incidence, sustained BMD increases, and reduced sCTX. The decrease in median sCTX is at the quantifiable limit (0.049 ng/ml) one month post-dose, remains low, and attenuates at the end of the 6-month dosing interval. Using 7 years of data from the FREEDOM study and its extension, we characterized changes in sCTX over time and the influencing factors. In the bone turnover marker and pharmacokinetic substudies, serum was collec...

IGF1 is an osteo-anabolic factor that stimulates osteogenic precursor cell differentiation. IGF1 is produced in bone in response to mechanical stimulation, but also in mechanically-stimulated muscle cells. IGF1 enhances the rate of mRNA translation in muscle cells via activation of the PI3K/AKT/mTOR pathway, thereby increasing in muscle mass. Therefore we hypothesized that IGF1 not just enhances osteogenic differentiation of precursors, but also stimulates protein syn...

see P487....