Bone Abstracts

Purpose: In X-linked hypophosphatemia (XLH), elevated serum FGF23 causes low serum phosphorus (Pi) and inappropriately normal 125-dihydroxyvitamin D (125(OH)2D) levels. We report PK and PD of KRN23 following single ascending dose administration in adults with XLH.Methods: 38 XLH patients with baseline FGF23≥30 pg/ml were randomized to receive a single dose of KRN23 (K) or placebo (P) either i.v. (0.003–0.3 mg/kg) or s.c. (0.1–1...

MicroRNAs are important regulators of gene expression with documented role in bone metabolism and osteoporosis. Moreover, the use of miRNAs constitutes potential therapeutic targets. Our aim was to identify miRNAs differentially expressed in fractured compared to healthy bone. Additionally, we performed a miRNA profiling of primary osteoblasts to assess the origin of the differentially expressed miRNAs. Total RNA was extracted from fresh femoral neck trabecular bone from women...

Little is known about the molecular mechanisms underlying the interaction between Sclerostin (SOST) and estrogen, showing an inverse relation in clinical data. Therefore, we investigated mechanisms by which estrogen modulates Sost expression at human osteoblastic cell level in association with BMP-2 signaling, which is a potential route of SOST induction. BMP-2 significantly induced SOST expression, which is suppressed by 17β-estradiol (E2) in human mesenchymal s...

Interleukin-34 (IL-34) is a newly discovered cytokine which regulates, like macrophage-colony stimulating factor (M-CSF), the differentiation/activation of the myeloid lineage. IL-34 and M-CSF are homodimers known to bind to the M-CSF receptor (M-CSFR) in a competitive manner. In this system, IL-34 can substitute for the M-CSF to induce osteoclastic differentiation. The aim of the present work was to study the functional relationships of these cytokines on cells expressing the...

Paget’s disease of bone (PDB) is the second most common metabolic bone disorder, after osteoporosis. Optineurin (OPTN) gene, which is located within the PDB6 locus, and appears to be upregulated by TNFα and NF-kB, has been found to be associated with PDB in several European populations with PDB in genome-wide association studies. Several nucleotidic variations in OPTN were previously associated with PDB and may contribute to PDB pathogenesis. Recently, we have identi...

Objective: Currently, majority of the osteoporotic patients are not diagnosed i) a new ultrasound based device (Bindex) has been recently introduced for osteoporosis (OP) screening and diagnostics at primary healthcare ii) Bindex measures cortical thickness and determines parameter called density index (DI). Thresholds for DI in OP assessment have been determined in Finnish-Caucasian (F-C) population (n=448) along the International Society of Clinical Densitometry (IS...

Objective: To evaluate the changes of health-related quality of life (HRQoL) 36 months after fracture in patients from Lithuania following vertebral or forearm fractures.Material and methods: Patients aged 50 years and older, with low energy trauma clinical vertebral fracture (VFx) or distal forearm fracture (FFx), enrolled and observed for 18 months in the International Costs and Utilities Related to Osteoporotic fractures Study (ICUROS) in Lithuania, w...

Ibandronate (IBN), a nitrogen-containing bisphosphonate, and eldecalcitol (ELD), an active vitamin D3 derivative, are used for osteoporosis treatment. Vitamin D3 often used in combination therapies, however, there are no reports on the effects of combined IBN and ELD treatment for osteoporosis.In this study, we examined the effects of combination treatment with IBN and ELD in aged ovariectomized rats. Eight-month-old Wistar-Imamichi...

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...

Introduction: Teriparatide is a potent anabolic drug that has demonstrated efficacy on fracture risk reduction in women with severe postmenopausal osteoporosis. Denosumab, designed to inhibit RANKL (RANK ligand), is a fully human MAB for the treatment of osteoporosis. BMD changes, measured by DXA, is an established tool for monitoring the effects of anti-osteoporotic therapy. Our purpose is to compare teriparatide vs denosumab efficacy on hip BMD variations, in postmenopausal ...