Bone Abstracts

see P208....

Clinical data suggest that the mTOR inhibitor everolimus may have bone protective effects in addition to its anti-tumor effects in women with ER+/HER2− metastatic breast cancer receiving hormone-ablative therapies. Based on these findings, we tested the hypothesis, whether everolimus exerts concurrent anti-tumor effects while protecting the skeleton in murine models. Thus, we assessed bone metabolism and anti-tumor effects in osteolytic cancer models upon exposure to eve...

Analysis of osteocyte function often uses promoter elements of osteocyte-specific genes i.e. SOST or Dentin-matrix-protein 1 (Dmp1) to overexpress genes or the Cre-recombinase for conditional deletion studies. However, evidence suggests that these promoters may not be osteocyte-specific, which would be critical for subsequent data interpretation. To investigate the selectivity of supposedly osteocyte-specific in vivo models, we crossed the 8kb-Dmp1-Cre mice (i) with A...

Objective: Describe UK regional variation in prescription of anti-osteoporosis drug therapy before and after a primary hip fracture during 1999–2013.Materials and Methods: We used primary care data (Clinical Practice Research Datalink) to identify patients with a hip fracture and primary-care prescriptions of any anti-osteoporosis drugs (bisphosphonates, strontium, denosumab, oestrogen therapy, SERMS, teriparatide) prior to primary hip fracture and ...

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: Pediatric vitamin D (25-hydroxyvitamin D - 25OHD) deficiency can lead to nutritional rickets and extra-skeletal complications. Compliance with daily therapy can be difficult, making high dose, short-term vitamin D (stoss) therapy attractive to correct vitamin D deficiency. We compared the effectiveness and safety of standard versus stoss therapy in treating childhood 25OHD deficiency.Study design: Children aged 2–16 years with 25OHD &#60...

Background: Denosumab (DMAB) is used in adults for the treatment of osteoporosis, giant cell tumour of bone, and cancer metastases. There are little data on paediatric use with clinical decision making reliant on adult data and clinical experience.Presenting problem: We have treated 33 children with DMAB: Perthes disease (n=9), avascular necrosis (n=17), osteoporosis (n=1), aneurysmal bone cyst (n=4) and giant cell tum...

Background: Atypical femur fractures (AFF) arise in the subtrochanteric and diaphyseal regions. Because of this unique distribution, we hypothesized that patients with AFF demonstrate specific geometrical variations of their femur whereby baseline tensile forces applied to the lateral cortex are higher and might favor the appearance of these rare stress fractures, when exposed to bisphosphonates.Methods: Subjects who sustained AFF, as defined by the ASBM...

see PP448....

Relatively little is known about immediate consequences of continuing vs interrupting long-term bisphosphonate treatment. This report describes changes in bone turnover and BMD in a 1-year, dose-finding trial of the calcium-sensing receptor antagonist MK-5442 in postmenopausal, BP-treated women, randomized to continued alendronate 70 mg weekly, switch to placebo, or switch to MK-5442. Recruited women (n=526) had taken alendronate for ≥12 months and an oral BP fo...