Bone Abstracts

Mutations in the C-propeptide cleavage site of both COL1A1 and COL1A2 cause dominant high bone mass (HBM) osteogenesis imperfecta (OI), characterized by bone hypermineralization. To elucidate the role of C-propeptide processing in bone formation, we generated heterozygous HBM mice in which both residues of the COL1A1 cleavage site were mutated to prevent cleavage by BMP1. HBM mice are smaller than WT in both weight and length and have extremely brittle bones....

Background: Fracture incidence rate and growth according to different glucocorticoid (GC) regimen in Duchenne Muscular Dystrophy (DMD) is currently unknown.Objective: To determine the extent of skeletal morbidity and the influence of GC regimen on fracture incidence rate and growth in a contemporary cohort of DMD in the UK.Method: Clinical details of 832 boys with DMD in the North Star database (2006–2015) from 23 centres were...

According to the literature data, some parameters of the femur (length of axis, length of femoral neck) are independent predictors of hip fractures, but such studies among Ukrainian patients are absent. The purpose of this study was to study age and gender features of some geometric parameters of the upper third of the hip in patients with intra- and extra-articular fractures of the femur.One hundred and seventy-four survey radiographs of the hip joints ...

Bone has recently emerged as a novel endocrine organ regulating glucose metabolism. Ectonucleotide pyrophosphatase/phosphodiesterase-1 (NPP1) controls bone mineralisation by generating the mineralisation inhibitor pyrophosphate. In clinical studies increased activity of NPP1 has been found in patients with insulin resistance, and it has been shown to directly inhibit the insulin receptor. We hypothesised that mice lacking NPP1 (Enpp1−/−) would exhibit im...

Purpose: To test whether bisphosphonates for osteoporosis reduce the risk of breast cancer.Background: Observational studies and meta-analyses find that women taking bisphosphonates have about a 1/3rd reduction in risk of breast cancer as soon as 1 year of treatment. This is plausible because bisphosphonates have in vitro anti-tumor activity and high doses of zoledronate reduce recurrence in women with breast cancer. However, observational studi...

see PP291....

STRUCTURE was a phase 3, open-label study evaluating the effect of romosozumab or TPTD for 12 months in women with postmenopausal osteoporosis transitioning from bisphosphonate therapy (NCT01796301). This study enrolled women with postmenopausal osteoporosis who had taken an oral bisphosphonate for ≥3 years prior to screening and alendronate in the year prior to screening; had a BMD T-score ≤−2.5 at the total hip (TH), lumbar spine (LS), or femoral neck (FN);...

Background: We have previously shown that MLO-Y4 osteocytes express a number of P2 receptors, respond to a broad range of nucleotides (e.g. UTP) by increasing intracellular calcium concentration and release ATP upon both mechanical and UTP stimulation. The aim of this study therefore is to investigate how the osteocytes release ATP and whether there is a difference in release pathway depending on the type of stimulus.Methods: ATP release was investigated...

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...

The relationship between BMD T-score and FX risk has not been established in patients receiving osteoporosis therapy. In the FREEDOM Extension study, continuous DMAb therapy for up to 10 years increased BMD levels with no therapeutic plateau at lumbar spine or TH [Bone et al, ASBMR 2015]. Such improvements would only be meaningful if associated with FX reductions. We investigated the relationship between TH BMD T-score and NVFX in women who received DMAb during FREEDOM and tho...