Bone Abstracts

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Extreme high bone mass (HBM) may be monogenic (e.g. due to mutations in SOST or LRP5) or polygenic, due to variants in the same genes determining bone mineral density (BMD) as found in the general population. We aimed to determine the genetic cause underlying HBM in an extreme HBM population.258 unexplained HBM cases (defined as L1 Z-score ≥+3.2 plus total hip Z-score ≥+1.2, or total hip Z-score ≥+3.2 and L1 <...

Autosomal dominant osteopetrosis type II (ADO2) is a rare osteosclerotic disease due heterozygous missense mutations of the CLC7 gene encoding the type seven chloride channel. Our two labs independently generated the first C57 black 6 (B6) mouse model of ADO2 by inserting the pG213R-clc7 mutation. Homozygous mice showed lack of tooth eruption and died within 30 days of age with severe osteopetrosis and central nervous system degenera...

Autosomal dominant type II osteopetrosis (ADO2) is a rare osteosclerotic disorder due to heterozygous missense mutations of CLC7 gene encoding the type 7 chloride channel. Our two labs (L’Aquila and Indianapolis) independently generated the first C57 black 6 (B6) mouse model of ADO2 by inserting the pG213R-clc7 mutation. We created pG213R-clc7 KI mice using a gene targeting approach. Homozygous mice showed lack of tooth eruption and died within ...

Objective: Evidence for further reduction of nonvertebral fracture (NVFX) beyond 3 years of antiresorptive therapy is limited. Since long-term denosumab (DMAb) treatment is associated with continuous increases in BMD and sustained fracture reduction, we analyzed the influence of femoral neck (FN) BMD after 3 years on NVFX rates.Methods: Long-term subjects received 7 continuous years of DMAb; cross-over subjects received 3 years of placebo (FREEDOM) and 4...

Mesenchymal cells alter and retain their phenotype during skeletal development through activation or suppression of signaling pathways. For example, we have shown that Wnt3a only stimulates osteoblast differentiation in cells with intrinsic osteogenic potential (e.g., MC3T3-E1 pre-osteoblasts) and not in fat cell precursors or fibroblasts (respectively, 3T3-L1 pre-adipocytes or NIH3T3 fibroblasts). Wnt3a promotes osteogenesis in part by stimulating autocrine production of the ...

Bisphosphonates (BPs) are used to treat bone diseases characterized by excessive bone resorption. However, BPs can negatively affect the jaw bone by causing osteonecrosis of the jaw. Previously, we showed that BPs differently affect long-bone and jaw osteoclast precursors. Administration of BPs in vivo reduced the number of jaw bone marrow cells, without affecting long-bone marrow cells. Yet, BPs increased bone volume and mineral density of both long bone and jaw. Her...

A clinical and densitometric study was performed in the group of 62 adults with cerebral palsy (CP) under institutionalized care in the district of Przemyśl (Southern Poland), 12 of whom had the history of 15 radiologically confirmed non-phalangeal limb fractures. The study assessed correlation between the prevalence of fractures and age, body mass, locomotor abilities determined by Gross Motor Function Classification System (GMFCS), presence of epilepsy, antiepileptic dr...

Aim: We present the case of a 36y female patient with multiple fragility fractures after the age of 21 and mutations in COL1A1, COL1A2 and GNAS genes.Material and methods: A 36y female patient with multiple fractures of the axial and appendicular skeleton was referred to us for consultation. The patient was born with hexadactyly of the left foot and had a history of mild thoracolumbar scoliosis (10°) and medium height (165 cm) with no other history ...