Bone Abstracts

Background and methods: Pigment epithelium-derived factor (PEDF) is a potent antiangiogenic factor, ubiquitously expressed and secreted in human tissues. Hypertrophic cartilage and osteoblasts express PEDF that binds to type I collagen and glycosaminoglycans in the extracellular matrix. Two rare forms of osteogenesis imperfecta (OI) with intact collagen synthesis are associated with PEDF deficiency. Histological observations revealed excessive osteoid formation and prolonged m...

Mutations in the C-propeptide cleavage site of both COL1A1 and COL1A2 cause dominant high bone mass (HBM) osteogenesis imperfecta (OI), characterized by bone hypermineralization. To elucidate the role of C-propeptide processing in bone formation, we generated heterozygous HBM mice in which both residues of the COL1A1 cleavage site were mutated to prevent cleavage by BMP1. HBM mice are smaller than WT in both weight and length and have extremely brittle bones....

High Bone Mass (HBM) osteogenesis imperfecta (OI) is caused by dominant mutations in the C-propeptide cleavage site of COL1A1 or COL1A2, characterized by bone hypermineralization. To elucidate the role of C-propeptide processing in bone mineralization and development, we generated heterozygous HBM mice with both residues (Ala-Asp) of the COL1A1 cleavage site substituted (Thr-Asn) to prevent processing by BMP1. Two, 6- and 12-month WT and HBM bones were examin...

Aim: Magnetic Resonance guided Focused Ultrasound Surgery (MRgFUS) is an invasive treatment able to control local disease and pain of bone tumors. Unfortunately, there is not any scientific evidence of the biological effect of MRgFUS treatment on tumor cells, especially in lower dose region, where tissues are only warmed to sub-lethal temperatures. Here we investigate the effect of in vitro MRgFUS treatment, at different levels of acoustic energy (200–630 J), on ...

Objectives: Denosumab (Dmab) is a monoclonal antibody targeting RANKL administered by sub-cutaneous injection. Given its convenient mode of administration, our goal was to assess the safety and efficacy of Dmab compared to intravenous zoledronic acid (ZA) in pediatric osteoporosis.Methods: In this one-year pilot study (NCT02632916), children 4–16 years with low-trauma fractures due to osteoporosis were randomized 1:1 to receive ZA 0.025 mg/kg or Dma...

Objectives: Denosumab (Dmab) is a monoclonal antibody targeting RANKL administered by sub-cutaneous injection. Recent reports have raised concern about the ‘rebound phenomenon’ (hypercalcemia and increases in bone turnover markers, BTM) following Dmab in adults, and during treatment in children with osteogenesis imperfecta. The purpose of this report was to explore this phenomenon in children with osteoporosis associated with lower bone turnover.<p class="abstext...

Introduction: Dual X-ray Absorptiometry (DXA) is currently the best technique available to evaluate bone mass, enabling the diagnosis of osteoporosis, the prediction of fracture risk and monitoring.Clinical good practices consider as preferred measuring sites the lumbar (L1–L4) and proximal femur (neck and total). The vertebral morphometry is a quantitative method for the diagnosis of vertebral fractures based on measuring vertebral heights.<p...

Despite widely accepted classical mechanical theory of buttresses as a load bearing areas in the midfacial skeleton, the data related to its microstructural adaptation on functional demands are scarce. In this study we investigated microstructural features of the different regions in the facial bones in relation to the occlusal load dissipation using a combination of finite element analysis (FEA) and micro-CT analysis (μCT). The FEA was performed on the model of the dry h...

Chondrosarcomas are cartilage-forming, poorly vascularized tumors. With an estimated annual incidence of 1 in 200 000, they represent the second malignant primary bone tumor of adults after osteosarcoma. These tumors are resistant to chemotherapy and radiotherapy, surgical excision remaining the only therapeutic option. However, very few cell lines and animal models are available, and the mechanisms behind their chemoresistance remain largely unknown. Our goal was to establish...

IκB Kinase β (IKKβ), a key component of NFκB signaling, plays an important role in bone disease and cancer. Genetic and pharmacological inhibition of IKKβ/NFκB signaling increase bone mass and protect against ovariectomy- and inflammation-induced bone loss. Here, we describe a previously unknown role of the IKKβ/FoxO3a axis in bone metastasis associated with breast cancer. We observed that IKKβ expression is prevalent in invasive breast ...