Bone Abstracts

In clinical studies, denosumab (DMAb) administration up to 8 years is associated with continued increases in bone mineral density (BMD) and low fracture incidence despite persistently low bone turnover markers and limited iliac crest tetracycline labelling (Papapoulos 2013). We tested the hypothesis that, with persistently low bone remodelling, BMD increases may result from a non-remodelling dependent mechanism to accrue bone matrix. We examined the fluorochrome labelling patt...

Introduction: The effectiveness of intravenous pamidronate was assessed independently and in combination with corrective osteotomy surgery for lower extremity deformities in children with osteogenesis imperfecta.Methods: Orthopaedic treatment was conducted in 21 patients with OI (type I–ten patients, type III–11 patients), including 13 males and eight females with mean age 9.4±0.6. All patients received calcium supplements and active forms...

Multiple myeloma (MM) bone disease is characterized by lytic bone lesions that contribute to patient morbidity and mortality after patients are in complete remission. The mechanisms mediating this long-term osteoblast (OB) suppression are poorly understood. We hypothesized that MM cells induce epigenetic changes at the Runx2 promoter in preOB bone marrow stromal cells (BMSC). We demonstrated that Gfi1, a transcriptional repressor of Runx2 that is induced in B...

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...

Due to its huge socio-economic impact a better understating of osteoporotic fracture healing is crucial.Thirty-one female merino land sheep were randomly divided into four groups. (i) Untreated control-group (C, n=8); (ii) bilateral ovariectomy (OVX, n=7); (iii) OVX and calcium-deficient diet (OVXD, n=8); and (iv) OVXD and additional biweekly corticosteroid injections (OVXDS, n=8). Drill-hole defects (7.5 mm in diamete...

Objectives: Two important goals of the Rare Diseases Clinical Research Network Brittle Bone Disorders Consortium (RDCRN BBD) are i) to perform collaborative clinical research in brittle bone disorders including a longitudinal observational study driven by genotypic association and ii) to explore use of the PROMIS tool to provide valid quality of life (QOL) measures in individuals with Osteogenesis Imperfecta (OI). This work has been motivated by the fact that all current outco...

Cole-Carpenter syndrome (CCS) is commonly classified as a rare Osteogenesis Imperfecta disorder. This was following the description of two unrelated patients with very similar phenotypes who were subsequently shown to have a heterozygous missense mutation in P4HB. Here, we report a 3-year old female patient who was diagnosed with a severe form of OI. Exome sequencing identified the same missense mutation in P4HB as reported in the original cohort, thus reinfo...

Background: Osteoporosis is common in subjects with Duchenne muscular dystrophy (DMD). Studies in paediatric DMD identified a high frequency of fragility fractures but there are no studies in the adult population. Recent updated international standards of care (2018) for children and adults with DMD recommend the following for bone monitoring:- Lateral thoracolumbar spine x-rays to screen for vertebral fracture (1–2 yearly if on glucocorticoid; 2&#1...

The autophagy protein LC3 is necessary for bone resorption by osteoclasts, although it has been suggested that this may be through a novel, autophagy-independent process, by promoting lysosomal fusion at the ruffled border (RB). This process would be analogous to LC3-associated phagocytosis (LAP), in which LC3 is acquired by phagosomes through an autophagy-independent process, and controls phagosome maturation by promoting fusion with lysosomes. We have investigated this possi...

Elevated levels of circulating serotonin have been reported to decrease bone mineral density1. Conversely, reduced serotonin (5HT) in mice lacking TPH1, the rate limiting enzyme for 5HT synthesis, was reported to be anabolic to the skeleton with high osteoblastic activity2. However, in other studies TPH1 deletion led to either an initial increase in BMD due to inhibition of osteoclastic bone resorption3, or had no bone effect4</su...