Bone Abstracts

The selective cathepsin K inhibitor odanacatib (ODN) is currently in development for the treatment of postmenopausal osteoporosis. Our goal was to evaluate the effects of ODN vs alendronate (ALN) on bone mass and strength of lumbar vertebrae (LV) in orchiectomized (ORX) rabbits, a model of male osteoporosis. Adult male rabbits (11 months old) were subjected to sham- (n=20) or ORX-surgery (n=24/group) for 7.5 months before dosing initiated. ORX animals were ra...

Gla-rich protein (GRP) is a vitamin K-dependent protein, characterized by a high density of γ-carboxylated Glu residues and high calcium binding affinity. It was shown to accumulate in mouse and sturgeon cartilage and in sites of skin and vascular calcification in humans. Four alternatively spliced transcripts of the GRP gene (GRP–F1, F2, F3 and F4) were described in mouse chondrocytes and zebrafish. Osteoarthritis (OA) is a common degenerative joint disease...

Multiphoton microscopy (MPM) is a powerful approach to visualize live cells and tissues, including bone, in three dimensions and over time. To enable preclinical longitudinal monitoring of bone by intravital MPM we developed an animal window model of bone using existing tissue engineering strategies. Electrospun polycaprolactone scaffolds and human mesenchymal stem cells after osteoblastic differentiation, in vitro, were implanted into the mouse skin in the presence o...

Odanacatib (ODN), a selective oral inhibitor of cathepsin K, is in development for the treatment of osteoporosis. In the primary efficacy analysis of the Phase 3, Long-Term ODN Fracture Trial (LOFT; NCT00529373), ODN significantly reduced fracture risk compared with placebo in postmenopausal women with osteoporosis. Pre-specified subgroup analyses evaluated the efficacy of ODN in patient subgroups.Women aged ≥65 years, without baseline radiographic...

Clinical data suggest that the mTOR inhibitor everolimus may have bone protective effects in addition to its anti-tumor effects in women with ER+/HER2− metastatic breast cancer receiving hormone-ablative therapies. Based on these findings, we tested the hypothesis, whether everolimus exerts concurrent anti-tumor effects while protecting the skeleton in murine models. Thus, we assessed bone metabolism and anti-tumor effects in osteolytic cancer models upon exposure to eve...

Background: Cabozantinib (CBZ) is a receptor tyrosine kinase inhibitor with activity against MET, VEGFR2, FLT3, c-KIT, and RET. Pre-clinical studies in models of prostate cancer bone metastasis demonstrated that CBZ treatment induced both a suppression of tumour growth and an alteration in bone remodelling, suggesting that both tumour and bone microenvironment represented potential CBZ targets. This is the first study exploring the potential direct activity of CBZ in bone usin...

Rooibos (Aspalathus linearis) tea is a refreshing and caffeine-free tea indigenous to the Western Cape regions of South Africa. This tea, which is rich in polyphenols and antioxidants, has shown many beneficial effects in health, however, its anti-osteoclastogenic potential remains unexplored. In this study, the in vitro effects of an aqueous extract of fermented rooibos tea were examined on osteoclast formation and bone resorption in RAW264.7 murine macropha...

Objective: It is well known that monocytes differentiate into osteoclasts. However, we found that human dendritic cells (DCs) also differentiate to osteoclast-like cells and assessed the role of dendritic cell-derived osteoclast (DC-OC) in pathological processes of inflammatory diseases such as rheumatoid arthritis (RA).Methods: DC-OCs were differentiated from human monocyte-derived DCs in vitro. The function of DC-OCs was compared to human mono...

Site-specific osteoclasts (OC) and OC-like cells from different pathologies exhibit heterogeneity e.g. in the resorption machinery, influence of anti-resorptive drugs and response to local or systemic hormones e.g. PTH. The explanation for this is not known but different precursors, local regulation through osteoblasts (OB), osteocytes and extracellular matrix (ECM) could be involved. To study these differences a simple and reproducible cell model is an advantage in pre-clinic...

Periprosthetic osteolysis (PO) leading to aseptic loosening, is the most common cause of failure of total hip replacement (THR) in the mid- to long-term. Polyethylene (PE) particulates deriving from the wear of prosthesis liners are bioactive and are implicated in the initiation and progression of osteolysis. Evidence exists that cells of the osteoblast/osteocyte lineage respond to PE particles and contribute to the catabolic response by promoting osteoclastic bone resorption....