Bone Abstracts

Objectives: To assess safety and clinical efficacy during 1–34 parathyroid hormone treatment (1–34-PTH) in real clinical practice; to describe fracture outcome after 1–34-PTH discontinuation in real clinical practice.Methods: We performed an observational study in real clinical practice of all consecutive severe osteoporosis (sOP) patients referred to our Rheumatology Department from Feb’10 until Jan’14. All patients were referre...

In a meta-analysis by Estrada et al. (2012), 56 loci were found associated with BMD, 14 of which were also associated with osteoporotic fracture. Several of these genes belong to the Wnt signaling pathway, including two inhibitors: DKK1 and SOST.To better understand the role of these genes in BMD determination and fracture susceptibility, we aimed to explore their allelic architecture by resequencing all coding exons and flanking region...

Patients with osteoporotic fractures are frequently treated in trauma surgery. While fracture fixation is at the center of patient care, treatment of the underlying bone disorder is often not considered, thereby increasing the risk for subsequent fractures. Closing this treatment gap is therefore among the greatest challenges in modern trauma surgery. To address this problem, we established a fully structured, multidisciplinary, sector-spanning fracture liaison service (FLS), ...

Osteoclast-poor RANKL-dependent autosomal recessive osteopetrosis (ARO) is a rare bone disease characterized by an increase in bone density due to the failure of bone resorption by impaired osteoclast formation. Haematopoietic stem cell transplantation is not an effective therapy for this ARO form, since in bone RANKL is produced mainly by cells of mesenchymal origin. Whether also these cells, besides the osteoclast, are in some way affected by RANKL deficiency is not known. T...

Infantile malignant osteopetrosis (IMO) is a rare, lethal, recessive disorder characterized by dysfunctional osteoclasts. TCIRG1, encoding the osteoclast V-ATPase, is mutated in 50% of IMO patients. We have previously shown that the resorptive function in osteoclasts derived from IMO patients can be restored in vitro by expressing TCIRG1 using a lentiviral vector. In this study, we aim to investigate the cellular response to vector-derived TCIRG1 expression and to det...

Early-onset Paget’s disease of bone (ePDB), familial expansile osteolysis (FEO) and expansile skeletal hyperphosphatasia (ESH) are related syndromes caused by heterozygous tandem insertion duplication mutations within the signal peptide region of TNFRSF11a (encoding receptor activator of NFκB; RANK). Given that patients are always heterozygous for these mutations we have generated thirteen cell lines to investigate the molecular consequences of these mutations in...

Bone is the primary site of metastasis for breast cancer, which leads mainly to osteolytic lesions, Cancer cells can expand into the bone for their ability to ‘dialogue’ with resident cells, interfering with the physiological processes of bone turnover. In this study, a large-scale analysis comparing gene expression of biopsies of bone and visceral metastases from human breast cancer patients showed that the receptor (G protein-coupled) activity modifying protein-2 (...

Objectives: The Brtl mouse, a unique model for the autosomal dominant forms of osteogenesis imperfecta was used to prove the feasibility of a lentiviral-shRNA-based strategy to improve collagen quality by targeting the mutant Col1a1 allele at the point mutation responsible for the causative substitution Gly349Cys. The ability to specifically suppress the mutant allele should convert the moderate Brtl outcome to the mild one caused by quantitative defect.<p class="...

Objective: In many traumatic or pathological conditions, bone turnover is low and osteoclast activity is reduced or abolished. We developed innovative hydroxyapatite (HA) scaffolds carrying RANKL expressing cells with the aim of supporting bone resorption when this is defective. Membrane-bound (m)RANKL is cleaved into soluble (s)RANKL by MMP14. We hypothesized that the osteoclastogenic potential of RANKL-producing cells could be improved if they were seeded on scaffolds engine...

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...