Bone Abstracts

Postmenopausal women with early stage hormone-receptor-positive breast cancer (EBC) are standardly treated with aromatase inhibitors (AIs). However, one side-effect of AIs treatment is a decrease in bone mineral density (BMD) and an increased risk of fracture. The objectives of this study were to examine: i) changes in bone formation (N-terminal propeptide of type I procollagen; PINP) and bone resorption (cross-linked C-telopeptides of bone type I collagen; CTX) markers, as we...

Osteoporosis is a frequent disease leading to an increased risk of fractures caused by a systemic impairment of bone mass, strength, and microarchitecture. Given the emerging role of the Wnt signaling pathway in bone biology, we focused on the function of the important Wnt inhibitor dickkopf-1 (Dkk-1) and examined how the deletion of Dkk-1 solely in osteoblasts or osteocytes influences bone homeostasis. Therefore, we used the Cre-LoxP recombination system and crossed Dkk-1-flo...

Breast cancer is the most frequent malignancy in women and frequently results in osteolytic bone metastases. Amino-bisphosphonates are a standard bone protective therapy and, similarly to statins, inhibit the mevalonate pathway that is crucial for posttranslational protein modifications (farnesylation and geranylation). Direct anti-tumor effects of amino-bisphosphonates and statins have been suggested but high concentrations are necessary to achieve meaningful effects. Our stu...

Wnt proteins and their cognate receptors play a significant role in malignant diseases, in particular in prostate cancer (PCa). We previously showed that WNT5A inhibits PCa cell proliferation and induces apoptosis in vitro, leading to reduced PCa growth in vivo. However, the involved receptors remain unknown. Here, we determine the role of two Wnt receptors (FZD8, RYK) and their influence on the WNT5A-induced effects on PCa cells.The ex...

α2C Evidences demonstrate that sympathetic nervous system (SNS) activation causes osteopenia via β2-adrenoceptor (β2-AR) signaling. In a recent study, we showed that female mice with chronic sympathetic hyperactivity due to double knockout of adrenoceptors that negatively regulate norepinephrine release, α2A-AR and α2C-AR (α2A/α2C-ARKO), present an unexpected phenoty...

Strontium ranelate is a promising drug used in the treatment of osteoporosis. This drug has a unique dual effect on bone turnover, simultaneously increasing bone formation by osteoblasts (anabolic effect) and decreasing bone resorption by osteoclasts (antiresorptive effect). The goal of this study was to evaluate: i) anabolic effects of strontium ranelate on the formation of bone-like mineralized matrix in osteoblast cell cultures and ii) changes the drug could cause on the ma...

Objective: We constructed height growth curves for children with XLH from birth to early adolescence, a majority of whom received conventional therapy consisting of multiple daily doses of oral phosphate and active vitamin D.Methods: Growth data from four clinical studies were pooled to construct the growth curves. UX023-CL002 was an observational, retrospective chart review of 103 children with XLH, 1–14 years of age. Pre-treatment data were collec...

Objectives: XLH features renal phosphate (Pi) wasting, hypophosphatemia, rickets, and skeletal deformities from elevated circulating levels of fibroblast growth factor 23 (FGF23). KRN23, an investigational fully human monoclonal antibody, binds FGF23 and inhibits its action. Our Phase 2 study of KRN23 in XLH children (ages 5–12 years) is demonstrating improvements in serum Pi and rickets. Here we present our Phase 2 trial evaluating the efficacy and safety of KRN23 in you...

The pathogenesis of skeletal fragility in diabetes mellitus is poorly defined and efficient therapies are limited. Zucker diabetic fatty (ZDF) rats with type 2 diabetes mellitus display low bone mass and delayed bone defect healing. We tested whether intermittent treatment with human parathyroid hormone 1–84 (PTH) increases bone mass and bone defect regeneration in diabetic rats.A subcritical gap defect was created at the femur of 10 weeks old diabe...

Although bone morphogenetic protein 6 (BMP6) is known for its ability to induce growth of bone and cartilage, recent studies identified BMP6 as a key endogenous regulator of hepcidin expression and iron metabolism. Here, we examined BMP6 presence in the serum and investigated whether circulating levels of BMP6 may reflect body iron status. First, we showed by liquid chromatography–mass spectrometry (LC–MS) and western blotting that BMP6 is present in the circulation ...