Bone Abstracts

Introduction: The fat-soluble and vitamin K2 homologe Menaquinone-7 (MK-7) is needed for post-translational modification of proteins essential in blood coagulation, and in metabolic pathways in various tissues like bone. Recent studies found an association between long-term anticoagulant treatment (OAC) and reduced bone quality due to reduction of active osteocalcin. OAC is often linked to an undesired soft-tissue calcification in both children and adults and may lead to incre...

Molecules secreted by the osteoclast or ‘clastokynes’ are essential to stimulate bone formation by osteoblasts. Treatments with bisphosphates and Denosumab target osteoclast survival and differentiation. This suppresses bone turnover and is suspected to increase the risk of atypical fractures in the long term. A solution to overcome this is to develop strategies that target selectively the activity of osteoclasts without affecting their survival or differentiation. S...

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...