Bone Abstracts

Epigenetic mechanisms regulate gene expression and are heritable through cell divisions even though they do not involve modifications in the gene sequence. They include methylation and other chemical modifications of cytosine nucleotides, histone posttranslational modifications, microRNAs and other non-coding RNAs. Most cytosines in the human genome are methylated, particularly in the inactive, tightly packed, heterochromatin of autosomes, and the inactivated X-chromosome in f...

Blood vessels and bone display spatial and functional relationships. While the coupling of angiogenesis to bone formation during modeling situations is well documented, the vessels roles in bone remodeling, although widely acknowledged, remain poorly explored. In order to image and quantify the bone vessel network in rodents, we contrasted the vascular bed with barium sulfate, followed by histology or either conventional or synchrotron radiation micro-computed tomography. We s...

Skeletal diseases are a large and diverse group of rare monogenic phenotypes and there are more than 450 unique and well-characterised chondrodysplasia phenotypes that range in severity from relatively mild to severe and lethal forms. Studying these genetically tractable chondrodysplasia phenotypes provides insight into disease pathways that may be relevant to the more common and polygenic forms of OA.Pseudoachondroplasia (PSACH) and multiple epiphyseal ...

Insulin-like growth factor 1 (IGF-1) is known to be a predictor of future osteoporotic fractures. Insulin-like growth factor binding protein 1 (IGFBP1) regulates the bioavailability of IGF-1 and thus in reason IGFBP1 also could be a fracture predictor. To our knowledge there are no previous studies published on the relation between the serum concentration of IGFBP1 and fractures.This is a population-based prospective cohort study on 351 Swedish women age...

Epidemiological studies suggest that patients using proton pump inhibitors (PPIs) have increased fracture risk. We have previously shown that H+/K+ATPase beta-subunit knockout (KO) mice have reduced BMD, BMC and mechanical bone strength compared to WT. Like users of PPIs, these mice have elevated serum gastrin levels due to high gastric pH. We wanted to study whether elevated gastrin influences bone quality in these mice.Female KO and WT mice aged 6 week...

Background: Treatments that result in greater increases in bone mass of normal quality by increasing bone formation rather than decreasing resorption are needed. Abaloparatide is a synthetic analog of PTHrP1-34 that has shown strong efficacy to increase bone mass and bone strength in animals. We conducted two phase 2 placebo-controlled studies both of which included abaloparatide 80 μg sc daily (ABL) in postmenopausal women with osteoporosis. Study 1 also inclu...

Objectives: A role for glucose-dependent insulinotropic polypeptide (GIP) in controlling bone mass and strength has previously been reported. However, the rapid degradation of GIP in the bloodstream by the dipeptidyl peptidase-4 enzyme precludes therapeutic use. To circumvent this problem, a series of N-terminally modified GIP agonists have been developed. The aim of the present study was to investigate the effects of 28-day treatment with N-AcGIP on bone microarchitecture and...

The regeneration of traumatized, damaged or lost bone is still a major clinical and socio-economical problem. Bone-tissue engineering approaches involve culturing mesenchymal stem cells (MSCs) on scaffolds, in order to create a 3D microenvironment in which MSCs are able to generate functional tissues and regulate foreign body reaction to implanted construct. Excessive or non-resolving inflammation, characterized by the presence of monocytes, macrophages and giant cells, makes ...

Human mesenchymal stromal cells (hMSC) have been investigated as a clinical therapy to promote tissue repair. However, the disappearance of grafted cells soon after engraftment suggests that hMSC could principally act as initiators of repair through paracrine mechanisms.The aim of this study was to evaluate the relative contribution of grafted hMSC and host cells in promoting bone tissue repair. We isolated hMSC from three bone marrow (BM) donors, then d...

Purpose: In X-linked hypophosphatemia (XLH), elevated serum FGF23 causes low serum phosphorus (Pi) and inappropriately normal 1,25-dihydroxyvitamin D (1,25(OH)2D) levels. We report safety, tolerability and biochemistry markers following single ascending dose administration of KRN23 in adults with XLH.Methods: 38 XLH subjects with baseline FGF23≥30 pg/ml were randomized to receive single doses of KRN23 (K) or placebo (P) either (0.003&#15...