Bone Abstracts

Background: There are no models for estimating risk of fracture in patients taking treatments for osteoporosis. Knowing a patient’s risk of fracture during treatment may help make future treatment decisions; therefore, the development of on-treatment fracture risk models is needed.Methods: To assess on-treatment fracture risk, the analysis included subjects who received denosumab (DMAb) 60 mg Q6 every 6 months for at least 1 year in either FREEDOM o...

Denosumab subcutaneous administration every 6 months reduced the incidence of new fractures in postmenopausal women with osteoporosis by 68% at the spine and 40% at the hip over 36 months compared with placebo in the FREEDOM study (Cummings et al., NEJM, 2009:361:756). This efficacy was supported by differential improvements from baseline in vertebral and femoral strength at 36 months (18.2 and 8.6%, respectively) estimated by an established voxel-based finit...

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Bone strength is influenced by cortical thickness, area, mass and porosity, all of which contribute to nonvertebral fracture risk. Cortical porosity is one parameter of structural decay associated with bone fragility. This is caused by unbalanced and accelerated remodelling of Haversian units which enlarge, coalesce and fragment the cortex. Antiresorptive therapies will limit progression of cortical porosity; reducing existing porosity would be a goal for those already at incr...

Low fracture (FX) incidence has been demonstrated in women with postmenopausal osteoporosis (PMO) treated with DMAb for up to 10 years in the FREEDOM extension [Bone ASBMR 2015]. Bone biopsy-based assessment of DMAb’s effects at the tissue level has demonstrated a low remodelling rate consistent with DMAb’s mechanism of action (Reid JBMR 2010; Brown JBMR 2014). From FREEDOM, we report the effects of DMAb on bone matrix mineralization in women who un...

Fibrodysplasia ossificans progressiva (FOP) is a rare debilitating genetic disease characterized by abnormal progressive heterotopic endochondrial ossification of soft tissues. FOP results from mutations in the intracellular domain of the type I BMP receptor ACVR1 (ALK2) the most common of which is R206H. FOP mutations alter the sensitivity of ACVR1 to Activin A from an antagonist to an agonist. We have previously shown that Activin A is necessary and sufficient for driving he...

Objectives: Clinicians practicing in long-term care (LTC) face unique challenges caring for frail elderly individuals including multiple co-morbidities, polypharmacy, and end of life care, and practice guidelines typically do not address this population. Guidance regarding the management of osteoporosis and fracture prevention in LTC, a high-risk population, is needed.Materials and methods: A survey of LTC physicians informed key questions and outcomes, ...

FOP is an autosomal dominant disorder characterized by early onset, episodic and progressive ossification of skeletal muscle and associated connective tissue. FOP is driven by mutations in the intracellular domain of ACVR1 (ALK2), the most common of which is R206H. However, rare FOP causing mutations exist throughout the GS and the kinase domain of Acvr1. Several of these mutations result what appears to be a more severe FOP phenotype that includes significant developmental ab...

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Members of the Rho family including small GTPase Cdc42 have been shown to play multiple roles in cell regulation, including regulation of cytoskeletal organization, cell migration, proliferation, and apoptosis. However, their tissue-specific roles in vivo, especially in limb bud mesenchyme, remain largely unknown. Herein, we report that conditional deletion of Cdc42 in AER dose not change the limb development, however, knockout of Cdc42 in mesenchymal stem cells of li...