Bone Abstracts

Objectives: Achondroplasia (ACH), the most common form of human dwarfism, is caused by a gain-of-function mutation in the fibroblast growth factor receptor 3 (FGFR3) gene, a key negative regulator of endochondral ossification. C-type natriuretic peptide (CNP) inhibits the FGFR3 pathway and thereby promotes proliferation and differentiation of chondrocytes to promote bone growth. TransCon CNP is a prodrug designed to provide continuous exposure to CNP to optimize efficacy with ...

Background: Most patients with hypoparathyroidism are controlled under conventional treatment with calcium and vitamin D analogues. However, this treatment may be difficult to manage, especially in patients with ADHH who have an increased risk of nephrocalcinosis and chronic renal insufficiency. ADHH is caused by activating mutations in the calcium-sensing receptor (CaSR) resulting in suppressed PTH secretion and decreased calcium reabsorption within the thick ascending limb o...

The P2Y14 (purinergic receptor P2Y, G protein coupled, 14) receptor for UDP-glucose and other UDP-sugars has been implicated in the regulation of the stem cell compartment as well as neuroimmune function. However, the role of P2Y14 in osteoclast formation is completely unknown. We found that RANKL selectively induced P2Y14 among seven mammalian P2Y receptors when analysed at both the mRNA and protein level, but inhibitors of the MAP pathway suppressed induction of P2Y14 protei...

Objectives: Hypophosphatasia (HPP) is the rare inherited metabolic disease caused by low tissue nonspecific alkaline phosphatase activity. HPP manifests a wide spectrum of complications, which may include HPP-related rickets and compromised physical function in children.Methods: We report on clinical gait assessments based on archival video recordings of six children with onset of HPP symptoms at ≧6 months and documented HPP-related skeletal abnor...

The relationship between bone formation and blood flow is unclear. Recently, PTH was reported to activate production of nitric oxide (NO), a potent vasorelaxing agent, in endothelial cells and we and others have confirmed a strong vasorelaxing action of PTH in vivo in the mouse. Here, we tested the hypothesis that a potent NO synthase inhibitor (L-NAME: NG-nitro-L-arginine methyl ester) may alter the effect of intermittent PTH (iPTH) on b...

Bone strength, hence fracture risk, is dependent on bone geometry, microstructure and bone material level properties. We have reported that microstructure and material level properties contribute independently to the increase in bone strength in rats treated with strontium ranelate for 2 years, as evaluated by μCT-based Finite Element analysis.We investigated the effects of strontium ranelate (SrRan) treatment on bone material level properties of tr...

Introduction: Osteocalcin (OC) is a marker of bone formation but also seems to play a hormonal role in the regulation of glucose and energy metabolism. Recently, an association of BMI with a haplotype composed of three single nucleotide polymorphisms (SNPs) in the gene for OC, located on chromosome 1q22, was observed in ethnically homogeneous European pedigrees.Aim: The aim of the study was to test the association of these three polymorphisms in the gene...

Background: Pseudohypoparathyroidism (PHP) is a group of heterogeneous endocrine disorders characterised by hormone resistance, primarily to parathyroid hormone (PTH). The resistance is caused by defects in the GNAS gene, which encodes the Gsα protein that activates the cAMP pathway. PHP patients demonstrate elevated plasma PTH, hypocalcaemia, hyperphosphataemia with normal renal function. PTH resistance can be confirmed by Ellsworth-Howard test (PTH s...

Introduction: Loss in bone mineral density may occur soon after initiation of adjuvant therapy for hormone-receptor-positive (HR+), breast cancer (BC) and correlates with changes in hormone levels. Adding zoledronic acid (ZOL) to adjuvant treatment for BC can preserve/improve bone mineral density and delay disease recurrence; however, effects of ZOL on endocrine hormone levels are currently unclear.Methods: Probone II assessed the course of endocrine hor...

Objective: To examine the efficacy and safety of direct administration of zoledronate acid (ZOL) on local osteoporotic lesion of ovariectomized rats.Methods: Six weeks later after ovariectomy, 16 6-month-old female S.D. rats were divided into the two groups with no differences of body weight and BMD of the proximal tibia. In the group L, 50 μl ZOL at a dose of 67 μg/kg were locally injected into the bone marrow between the two dr...