Bone Abstracts

We previously evidenced a reduced response to i.v. pamidronate in Q15STM1 mutation carriers (Q15STM1+) with Paget’s disease of bone (PDB). In order to confirm and extend this observation, we investigated the effect of Q15STM1 mutation and polymorphisms in three genes associated with PDB (TNFRSF11A; OPTN; TNFRSF11B) on the response to bisphosphonates. First, a retrospective study was performed in 335 patients treated wi...

Osteogenesis imperfecta (OI) type V is caused by a unique dominant mutation (c.−14C>T) in IFITM5, which encodes BRIL, a transmembrane ifitm-like protein most strongly expressed in osteoblasts, while type VI OI is caused by recessive null mutations in SERPINF1, encoding pigment epithelium-derived factor (PEDF). We identified a 25-year-old woman with severe OI, whose dermal fibroblasts and cultured osteoblasts displayed minimal secretion of PEDF, but ...

Growing body of evidence shows that microRNAs play an important role in regulating bone mass. We investigated the cooperative microRNA-mRNA regulatory mechanism of peak bone mass in inbred strain of mice with different bone density using microarray analysis. Femur and tibia of 12-week old C3H/He (high bone density) and C57BL/6 (low bone density) were harvested to extract total bone RNAs for microarray. A total of 30 miRNAs were differentially expressed between bone tissue of C...

Transforming growth factor (TGF)-β1 is the most abundant growth factor in human bone. Several polymorphisms have been described in the TGF-β1 gene (TGFB1). We have previously shown that individuals with the CC genotype of the T29C polymorphism have higher bone mass at the femoral neck. The T29C polymorphism causes a change from leucine to proline at codon 10, which is located in the hydrophobic α-helical part of the signal peptide....

Loss of genomic maintenance contributes to aging, as exemplified by mutations in Ercc DNA repair proteins that lead to a plethora of progeroid syndromes of which some display accelerated bone loss. It is generally accepted that dietary restriction (DR) increases life span and improves organ function. We therefore assessed the impact of DR on life span and bone mass in WT and bona fide prematurely aging hypomorphic Ercc-deficient mice (Ercc1−/Δ).<...

Paget’s disease of bone (PDB) is the second most common metabolic bone disorder, after osteoporosis. Optineurin (OPTN) gene, which is located within the PDB6 locus, and appears to be upregulated by TNFα and NF-kB, has been found to be associated with PDB in several European populations with PDB in genome-wide association studies. Several nucleotidic variations in OPTN were previously associated with PDB and may contribute to PDB pathogenesis. Recently, we have identi...

Bone density (BMD) loss is a consequence of aromatase inhibitors (AI) treatment of breast cancer. B-ABLE cohort includes 391 postmenopausal women with early breast cancer starting AI therapy. Participants experienced a 1.98% (95% CI 1.54–2.42% P<0.0001) bone loss at lumbar spine (LS) and 1.24% (95% CI 0.81–1.67% P<0.0001) bone loss at femoral neck (FN) after 1 year on AI therapy and a 3.51% (95% CI 3.00–4.03% P<0.0001) bone...

Introduction: The fat-soluble and vitamin K2 homologe Menaquinone-7 (MK-7) is needed for post-translational modification of proteins essential in blood coagulation, and in metabolic pathways in various tissues like bone. Recent studies found an association between long-term anticoagulant treatment (OAC) and reduced bone quality due to reduction of active osteocalcin. OAC is often linked to an undesired soft-tissue calcification in both children and adults and may lead to incre...

Background: Osteoporosis is a hereditary multifactorial disease characterised by low bone mass leading to an increased susceptibility to fracture. Bone mineral density (BMD) is the most widely used predictor of fracture risk. Gene variants have been found associated with a low BMD and increased fracture risk; nonetheless studies have identified the relationship between susceptibility genes and fractures independent of BMD.Objective: Eight single nucleoti...

Osteoporosis is a common disorder with a partly genetic pathogenesis. Interaction between RANKL and its receptor RANK is essential in bone remodeling.We therefore investigated the effect of polymorphisms in the RANK and RANKL genes and interaction between the effects on bone mineral density (BMD) and vertebral fractures.The study was a case-control study with 462 osteoporotic patients and 336 controls. Ten polymor...

Objective: The enzyme methylenetetrahydrofolate reductase (MTHFR) is known to play an important role in the removal of circulating homocysteine via the methionine cycle. C677T polymorphism is associated with higher plasma homocysteine levels, which could affect collagen maturation. The aim of the present study was to examine possible associations of C677T polymorphism in the MTHFR gene with a variability of femoral (F-BMD), spinal BMD (S-BMD) together with circulating...