Bone Abstracts

Glucocorticoids (GCs) are widely used to treat chronic inflammatory diseases such as rheumatoid (RA) and lead to multiple side effects including glucocorticoid induced osteoporosis (GIO). Our work challenges the dogma that transrepression of pro-inflammatory genes by the glucocorticoid receptor (GR) is solely responsible for reducing inflammation, whereas transactivation of genes is causing side effects.Using conditional and function selective mutant mic...

Background: Lean and bone mass are heritable traits with high phenotypic correlation (rho=0.44), likely reflecting the underlying mechanical and biochemical interactions between tissues.Aim: Estimate the shared heritability (genetic correlation) of both traits in children and identify genetic determinants displaying pleiotropic effects on lean mass and bone mass accrual.Methods: Participants make part of two prospective po...

Multiple myeloma is characterized by extensive bone marrow tumour and destructive osteolytic lesions. Both increased bone resorption and suppressed bone formation result in lesions and pathological fractures. Anti-resorptive therapies prevent further bone loss but patients continue to fracture, arguing for new therapies which increase bone strength. Anti-Sclerostin (Anti-Scl) is a potent stimulator of bone formation, is currently in clinical trials for osteoporosis, however it...

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Bruck syndrome, a disorder caused by bi-allelic mutations in either PLOD2 or FKBP10, is characterized by flexion contractures and bone fractures and shows strong clinical overlap with the brittle bone disease Osteogenesis Imperfecta. PLOD2 encodes the Lysyl hydroxylase 2 (LH2) enzyme, which is responsible for the hydroxylation of lysine residues in the type-I collagen telopeptides. This hydroxylation directs cross-linking of the collagen fibrils in t...

Osteogenesis imperfecta (OI) is a heritable bone dysplasia with collagen-related defects. Dominantly inherited OI is caused by structural defects in type I collagen or IFITM5, while recessive forms are caused by deficiency of proteins that interact with collagen for modification, folding or cross-linking. We have identified the first X-linked form of OI, caused by a defect in regulated intramembrane proteolysis (RIP). One type of RIP involves sequential cleavage of regulatory ...

Objectives: We evaluated the efficacy and safety of intravenous zoledronic acid (IV ZA) in children with glucocorticoid-induced osteoporosis (GIOP) through a randomized, placebo (PBO)-controlled trial.Methods: In this multi-national Phase 3 trial (NCT00799266), children 5–17 years of age with GIOP and low-trauma vertebral fractures (VF) were randomized 1:1 to IV ZA 0.05 mg/kg or IV PBO every six months for one year. Changes in lumbar spine areal bon...

Objectives: Denosumab (Dmab) is a monoclonal antibody targeting RANKL administered by sub-cutaneous injection. Given its convenient mode of administration, our goal was to assess the safety and efficacy of Dmab compared to intravenous zoledronic acid (ZA) in pediatric osteoporosis.Methods: In this one-year pilot study (NCT02632916), children 4–16 years with low-trauma fractures due to osteoporosis were randomized 1:1 to receive ZA 0.025 mg/kg or Dma...

Objectives: Denosumab (Dmab) is a monoclonal antibody targeting RANKL administered by sub-cutaneous injection. Recent reports have raised concern about the ‘rebound phenomenon’ (hypercalcemia and increases in bone turnover markers, BTM) following Dmab in adults, and during treatment in children with osteogenesis imperfecta. The purpose of this report was to explore this phenomenon in children with osteoporosis associated with lower bone turnover.<p class="abstext...

Objectives: To evaluate musculoskeletal trajectories in children with newly diagnosed Crohn’s disease (CD), and to determine whether children treated with anti-tumour necrosis factor-alpha antibody (anti-TNF, TREATED vs NAÏVE) had persistent deficits at two years.Methods: This was a single-centre prospective, observational inception cohort study. Children with CD underwent assessments within 6.5±9.5 days from diagnosis and annually for two...