Bone Abstracts

Gene deletion or treatments with a cathepsin K (CatK) inhibitor in mature preclinical models result not only result in lower bone resorption but also in higher bone formation (BF) on both remodeling and modeling surfaces. Although increased production of clastokines and matrix-derived growth factors may explain the increased BF at remodeling surfaces, the mechanisms for greater BF at modeling surfaces, including the periosteum, remain unexplained. We hypothesized that the abse...

Pparγ is a master transcriptional regulator of energy metabolism. We demonstrated that Dmp1-Cre/Lox-mice (KO) have increased bone mass and improved energy metabolism. Here we investigated if Pparγ-deficiency in Dmp1 cells can prevent high fat diet effects on these parameters. For this purpose, WT and KO male mice aged of 16 weeks received a high fat or chow diet (HF 60% vs CD 10% of fat) for 12 weeks. Lean and fat, bone structure, metabolic rate and tissue temperatur...

Periostin is a matricellular protein expressed in late osteoblasts/osteocytes, which levels increase in response to PTH and mechanical loading. In turn periostin contributes to modeling based bone formation while restraining bone remodeling. Periostin is also a substrate of cathepsin K and inhibition of periostin blunts the effects of cathepsin K inhibition on bone. Considering the important role of osteocytes and their cathepsin K expression on osteolysis during lactation, we...

In rural Gambian prepubertal children with low calcium intakes (mean 300 mg/day) we reported positive effects, sustained for at least a year (y), on bone mineral content (BMC) after 12 months supplementation with calcium carbonate to international levels1,2. The group was followed up regularly until the end of height growth, and supplementation did not affect height growth in the girls3. Our aim was to determine whether the supplementation altered the tim...

Biogenesis and function of microRNAs can be influenced by genetic variants in the pri-miRNA sequences leading to phenotype variability. The aim of this study was to identify osteoporosis-related SNPs by affecting the expression levels of mature microRNAs.The first approach was to perform an association analysis of putative functional SNPs located in pri-miRNA sequences of bone-related microRNAs with the lumbar spine and femoral neck (FN) bone mineral den...

Vertebral fractures (VF) in adults are the most common osteoporotic fracture, are powerful predictors of future fracture risk (hip X2; spine X5) and their prevalence increases as bone mineral density (BMD) declines. The most common imaging method for diagnosis is spinal radiography, but they can be identified fortuitously also on other imaging techniques performed for various clinical indications.1 Midline reformations of multi-detector CT (MDCT) scans of thorax and...

Background: We identified a family with early onset X-linked osteoporosis and fracturesMethods: We performed whole exome sequencing of the X chromosome in three affected members. After discovering a putative pathogenic variant we performed Sanger sequencing of all exons of this gene in other members of this family and in 95 unrelated men suspected of OI type I without COL1A1/2 mutations. We also genotyped a SNP in this gene (minor allele frequency 0.02) ...

It has been established that disturbances of intracellular signaling pathways strongly contribute to the oncologic process. Indeed, phosphatidylinositol-3-kinase (PI3K) became a key target in cancer therapy, due to its high frequency of mutation and/or gain of function of its catalytic subunits in cancer cells. In this context, we investigated the in vitro and in vivo effects of a new PI3Kα inhibitor, BYL719 (Novartis Pharma), on bone cells and its thera...

Osteosarcoma is the most common primary malignant bone tumor, characterized by osteoid production and/or osteolytic lesions of bone. Despite recent improvements in chemotherapy and surgery, the problem of non-response to chemotherapy remains and constitutes a poor prognosis parameter. Consequently new therapeutic strategies aim to improve the overall rate of survival. The present work investigated the therapeutic interest of a dual phosphatidylinositol-3-kinase (PI3K)/mammalia...

Objectives: Osteopenia is a complication of childhood cancer treatment but it is unknown to which extend this occurs in adult survivors, and which subgroups are at risk. We examined bone mineral density (BMD) and assed the relative importance of potential determinants of low BMD in very long-term adult survivors of childhood cancer.Methods: The single-center cohort study included 410 adult CCSs (median age at diagnosis: 6.6 years (range: 0–17 years)...