Bone Abstracts

Introduction: Bone metastases represent a frequent complication of breast cancer and are characterized by increased tumour-driven activation of osteoclasts and subsequent bone loss. Aminobisphosphonates inhibit osteoclast function and are established therapies of skeletal metastases. Similar to statins, they block the mevalonate pathway and are thought to have direct anti-tumour effects. Here, we report on the anti-tumour potential of a sequential inhibition of the mevalonate ...

Bisphosphonates (BPs) such as zoledronic acid (ZA) are widely used to treat bone diseases. The use of BPs can lead to osteonecrosis of the jaw (ONJ), but it is not clear why in particular the jaw bone is affected. Previously, it was shown that osteoclasts derived from different bone sites have different properties. We hypothesize that BPs have distinct effects on bone-site specific osteoclasts or precursors. To investigate this, female C57BL/6J mice were injected intraperitone...

Introduction: Dentinogenesis imperfecta (DI) is a common dental aberration in patients with osteogenesis imperfecta (OI). Mutations that cause abnormal collagen chains will cause more serious types of OI and it has been claimed that DI should be a marker for qualitative defected collagen. It has also been supposed that normal development of teeth may be more dependent on normal α2(I) than normal α1(I) chains which are encoded by COLIA2 and COLIA1 ge...

Denosumab (DMAb) significantly improves bone strength at the hip, estimated by FEA from QCT scans, from baseline (B/L) and vs placebo (Pbo) (Keaveny ASBMR 2010). We determined the extent and distribution of mass and thickness changes at the proximal femur, a key skeletal site for fracture risk, using a novel cortical bone mapping technique on the same serial QCT scans. A FREEDOM substudy included 80 women who underwent hip QCT scanning at B/L and months 12, 24 and 36 during DM...

Antenatal glucocorticoid (GC) injections are not only used to enhance fetal lung maturation in preterm children but also for the treatment of maternal conditions such as autoimmune diseases or infections. Animal models and clinical studies suggest that the regulation of the hypothalamic–pituitary–adrenal axis is altered in the offspring of GC-treated mothers with increased sensitivity to stress.Objective: The aim of this study is i) to define t...

Bone resorption and formation occur in a tightly regulated fashion reflecting the coupled activities of osteoclasts and osteoblasts. Several pathological conditions perturb this balance, including osteoporosis and skeletal metastases. In the case of metastases, the uncoupling of resorption and formation activities contributes to disseminated tumor cells homing to the bone and to tumor growth within the bone in highly localized regions. Therefore, a site-specific marker of bone...

Purpose: This combined qualitative and quantitative study aimed to investigate women’s personal reasons for and choices to decline the screening for osteoporosis. The ROSE study is a randomized prospective population-based trial investigating the efficacy of a screening program to prevent fractures in women aged 65–80 years.Methods: A triangulated approach combining data from interviews and questionnaire. 7020 questionnaires from the screening ...

Background: The tyrosine kinase inhibitor (TKI) imatinib is applied as front-line treatment in adult and pediatric patients with chronic myeloid leukemia (CML) in order to selectively inhibit the causative oncogenic BCR-ABL1 tyrosine kinase. However, TKIs exhibit off-target effects on further kinases involved in the regulation of bone metabolism. As consequence, pediatric patients display longitudinal growth retardation while on imatinib treatment. As CML is a rare disease in ...

Quantitative Computed Tomography (QCT) can be performed with different protocols. We investigated whether selection of spatial resolution, reconstruction method, and scanner type have an impact on measured treatment effects for different bone compartments.Methods: In a multi-center study, a group of 50 men, age 55.1 (range 25–78) undergoing 18 months of either osteoanabolic (n=25) or antiresorptive treatment (n=25) were scanned wit...

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...