Bone Abstracts

Autosomal dominant osteopetrosis type 2 (ADO2) is a rare genetic disease due to reduced osteoclast function. Clinical manifestations are variable, and in some cases the symptoms, including frequent fractures, osteomyelitis, hematologic and neural failures, are already evident during childhood and worsen with age. In 70% of cases, ADO2 is caused by heterozygous dominant negative mutations of the CLCN7 gene, encoding the Cl−/H+ antiporter type 7. We hypothesized that silen...

Breast to bone metastasis is a common incurable event during breast cancer progression. Identifying the molecular mechanisms at play is vital for the development of new therapies. Matrix metalloproteinases, such as MMP-2, are overexpressed in the bone metastatic microenvironment. Genetic ablation of MMP-2 demonstrated its importance of in driving osteolytic bone metastatic breast cancer and support the rationale for the development of a highly specific MMP-2 inhibitor for the ...

Objectives: ADO2 is a genetic bone disease induced by dominant negative mutations of the proton/chloride antiporter ClC7 encoded by the CLCN7 gene. In osteoclasts, ClC7 is crucial for lysosome function and resorption lacuna acidification. However, Clcn7 is expressed in several cell types in various organs, including brain, lungs, kidneys and spleen. Therefore, we asked whether Clcn7 mutations could affect other tissues beyond the bone.<p class="a...

Background: Surgical treatment of type 2 diabetes, specially in obese patients, has provided good results in the control of blood glucose and Hb1Ac although its effect on bone health is not clear. The aim of this study was to evaluate gene expression of bone remodelling markers in type 2 diabetic Goto-Kakizaki (GK) non-obese rats after gastrojejunal bypass and sleeve gastroplasty, and their relationship with hormonal parameters.Materials and methods: We ...

Pioglitazone is a drug of the thiazolidinedione (TZD) class used to treat type 2 diabetes mellitus. TZD is an agonist of peroxisome proliferator-activated receptor γ (PPAR-γ) that improves insulin sensitivity, glucose and lipid metabolism and inflammation. However, TZD induces bone marrow adiposity with suppression of osteogenesis, that could contribute to bone loss and osteoporotic fractures. β-Cryptoxanthin is a carotenoid with antioxidant properties abundant ...

Introduction: Currently, osteoporosis is mainly diagnosed through dual-enargy X-ray absorptiometry (DXA). However, DXA cannot be used for early diagnoses through population mass screenings because of issues related to ionizing radiation employment. Aim of this study is to perform a preliminary clinical validation of a new ultrasound (US)-based method for vertebral densitometry.Methods: A total of 270 women were included in this study according to the fol...

Objectives: The Brtl mouse, a unique model for the autosomal dominant forms of osteogenesis imperfecta was used to prove the feasibility of a lentiviral-shRNA-based strategy to improve collagen quality by targeting the mutant Col1a1 allele at the point mutation responsible for the causative substitution Gly349Cys. The ability to specifically suppress the mutant allele should convert the moderate Brtl outcome to the mild one caused by quantitative defect.<p class="...

Background: Proline and hydroxyproline account for ~25% of aminoacids in collagen., Prolidase (peptidase D (EC 3.4.14.9)), cleaves iminodipeptides with a C-terminal proline or hydroxyproline, playing a major role in collagen catabolism. Mice with prolidase deficiency (PD) present with varied phenotypes including reduced size compared to wild-type littermates. We measured structural and mechanical properties of bones in PD mice.Methods: Whole femurs from ...

Background: Osteoporosis in otherwise healthy children demands thorough study as it may be the first manifestation of an occult illness. When other diseases can be ruled out, juvenile idiopathic osteoporosis (JIO) is the purported diagnosis.PresentationWe report the case of an 8-year -old boy with no personal or family history of chronic disease who presented with sudden ankle pain unrelated to trauma and not responsive to rest and...

The cathepsin K inhibitor odanacatib (ODN) is a bone formation-sparing inhibitor of osteoclastic resorption activity. This drug is currently under development for the treatment of postmenopausal osteoporosis. To support the bone safety profile of ODN, we evaluated the effects of ODN on trabecular bone hard tissue properties in the estrogen-deficient model of the ovariectomized (OVX) rhesus monkeys. Animals (n=16/group, age 11–22 years) were treated immediately af...