Bone Abstracts

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...

Objective: To explore the characterization and risk factors of acute-phase response (APR) following a first-dose administration of 5 mg zoledronic acid for treatment of osteoporosis.Method: We conducted clinical data of the zoledronic acid users for treatment of osteoporosis in Department of Endocrinology, West China Hospital, Sichuan University from January 2009 to November 2012.Results: A total of 178 patients were eligible for i...

Aim & background: Evidence from genetic studies of osteoporosis and fracture risk indicate that bone mineral density (BMD) is genetically controlled. The low-density-lipoprotein-related receptor 5 (lrp5) gene is a known co-receptor in the canonical Wnt bone formation regulatory pathway. Although mutations found in this gene have been shown to regulate BMD in humans, and Lrp5 knockout mice had reduced bone mass, its role in the bone development/bone acquis...

Objective: To comparing the role of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) in fat and bone communication.Methods: Male wild type (WT) mice, IL-6 knockout (IL-6−/−) mice, and tumor necrosis factor alpha (TNF-α) were fed with either standard diet (SD) or high fat diet (HFD) for 12 weeks. Bone mass and bone microstructure were evaluated by micro-CT. Gene expression related to lipid and bone metabolisms ...

Indoxyl sulfate (IS) is one of a number of protein-bound uremic toxins that accumulate in patients with chronic kidney disease. Current conventional hemodialysis is ineffective at removing this toxin. Although IS may impair osteoblast function and induce abnormalities of bone turnover or arthropathy, the effects on knee joint tissue by IS has not been investigated yet. The present studies have been carried out to test the IS effects on synovial fibroblasts, meniscal fibrochond...

Odanacatib (ODN), a selective and reversible cathepsin K inhibitor was shown to histomorphometrically reduce trabecular (Tb) and intracortical (Ic) bone remodeling while preserving endocortical (Ec) and stimulating periosteal (Ps) bone formation (BF) in monkeys. Here, we investigate the bone site specific mechanism of ODN on bone modeling (Mo) versus remodeling (Re)-based osteons. Rhesus monkeys (13–19 yrs, n=8–11/group) were ovariectomized and treated with ...

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...

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A hallmark of Multiple Myeloma is skeletal colonization resulting in painful osteolytic lesions. Matrix metalloproteinase-13 (MMP-13) is a type-1 collagenase largely expressed by mesenchymal stromal cell (MSCs) in the bone tissue. In agreement, immunohistochemical staining of human myeloma biopsies demonstrated the localization of MMP-13 to the stromal compartment with expression in a subset of myeloma cells. This observation was further supported by studies showing that co-cu...

Identifying novel approaches for enhancing osteoblast (OB) differentiation of human skeletal (mesenchymal) stem cells (hMSC) can lead to development of novel anabolic agents required for efficient bone formation. Transforming growth factor-βs (TGF-β1, 2, 3) are one of the most abundant growth factors in bone and play a key role in regulating bone remodeling. Canonical TGF-β signaling inhibits, whereas components of the non-canonical TGF-β signaling (e.g. Ak...