Bone Abstracts

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...

Selective p38α inhibitors have been found to prevent bone loss induced by estrogen deficiency but implicated mechanisms remained to be identified. The p38 MAPK pathway has been suggested to influence bone resorption at different regulatory levels. In osteoblasts, p38α has been reported to be involved in the production of osteoclastogenic interleukin 6 and Rankl in response to various bone-resorptive agents in vitro. Therefore, we investigated whether p38&#94...

see PP163....

Here we identify the lipolytic enzyme hepatic lipase (HL, encoded by Lipc) as a novel cell-autonomous regulator of osteoblast function. In an unbiased genome-wide expression analysis, we find Lipc – which was formerly thought to be expressed almost exclusively by the liver – to be highly induced upon osteoblast differentiation, as verified by quantitative Taqman analyses of primary osteoblasts in vitro and of bone samples in vivo. ...

Using a longitudinal observational study with two evaluations and a 1 year follow-up interval, we investigated the influence of everyday physical activity (PA) and skeletal geometry in bone mineral density (BMD) and bone mass distribution at the proximal femur (PF) in 96 girls and 81 boys (10–12 years). Whole body and left hip DXA scans were used to derive geometric measures of the pelvis (inter acetabular distance – IAD) and PF (abductor lever arm – ALA). BMD w...

Background: Paget’s disease of Bone (PDB) has a strong genetic component and a candidate locus for the disease has been identified on chromosome 14q32, tagged by rs10498635 located within RIN3 (Albagha et al, Nat Genet 2011). RIN3 encodes a protein that acts as a guanine nucleotide exchange factor for Rab5b and Rab31. Here we investigated the candidacy of RIN3 as a predisposing gene for PDB.Methods: We studied expression of RIN3 by quantita...

see PP292....

Osteoporosis is common in rheumatoid arthritis (RA). Since osteoblasts express receptors for CXCL8 and CCL20, which are produced by inflammatory cells around the inflamed joints in RA, we hypothesized that CXCL8 and CCL20 contribute to osteoporosis in RA by affecting osteoblast proliferation, differentiation, and osteoblast-osteoclast communication.Primary human osteoblasts were cultured±CXCL8 (2–200 pg/ml) and CCL20 (5–500 pg/ml) for 14 d...

Introduction: Despite similarities in upfront treatment, impairment of bone mineral density(BMD) varies in long-term adult survivors of childhood cancer (CCS). We studied for the first time whether genetic variation is involved in impairment of BMD in adult long-term CCS.Method: This cross-sectional single-center cohort study included 334 adult CCS (median follow-up time: 15.2 years (range 5.1–39.8); median age at follow-up: 26.1 years (range 18.1&#...