Does the gene polymorphism influence the efficacy of denosumab therapy in postmenopausal osteoporosis?

Introduction: One of the challenges of personalized medicine is a departure from traditional pharmacology toward individualized, genotype-based therapies. Postmenopausal osteoporosis is a prevalent condition requiring intensive treatment, whose effects are measurable only after a long time, and the goal is bone fracture prevention. This study aimed to determine the influence of gene variation on anti-osteoporotic one-year treatment with denosumab in 63 Polish women with postmenopausal osteoporosis.

Shoulder arthropathy secondary to syringomyelia: systematic review.

Purpose: The purpose of this study was to collect and evaluate clinical and radiological evidence on shoulder neuroarthropathy (NA) in syringomyelia (SM) that may support the management and treatment of patients with this condition.

Materials And Methods: This systematic review is based on the analysis of reports available in PubMed, Embase, Cochrane Database of Systematic Reviews and Cochrane Central Register of Controlled Trials using the following keywords: syringomyelia, neuroarthropathy, Charcot joint and shoulder degeneration. Thirty-nine publications were found presenting case reports or case series meeting our criteria.

Inositol triphosphate-triggered calcium release from the endoplasmic reticulum induces lysosome biogenesis via TFEB/TFE3.

Lysosomes serve as dynamic regulators of cell and organismal physiology by integrating the degradation of macromolecules with receptor and nutrient signaling. Previous studies have established that activation of the transcription factor EB (TFEB) and transcription factor E3 (TFE3) induces the expression of lysosomal genes and proteins in signaling-inactive starved cells, that is, under conditions when activity of the master regulator of nutrient-sensing signaling mechanistic target of rapamycin complex 1 is repressed. How lysosome biogenesis is triggered in signaling-active cells is incompletely understood.

Shoulder arthropathy secondary to syringomyelia: case series of 10 patients.

Purpose: Neuroarthropathy is a progressive joint degeneration secondary to neurological diseases. In the upper extremity, the shoulder is the most exposed, and it is mainly caused by syringomyelia. This condition is rare; therefore, the literature has documented only a few case reports or case series of small groups of patients.

Inositol triphosphate-triggered calcium release blocks lipid exchange at endoplasmic reticulum-Golgi contact sites.

Vesicular traffic and membrane contact sites between organelles enable the exchange of proteins, lipids, and metabolites. Recruitment of tethers to contact sites between the endoplasmic reticulum (ER) and the plasma membrane is often triggered by calcium. Here we reveal a function for calcium in the repression of cholesterol export at membrane contact sites between the ER and the Golgi complex.

Clinical and radiological examination of bony-mediated shoulder instability.

The coexistence of glenoid and humeral head bone defects may increase the risk of recurrence of instability after soft tissue repair.Revealed factors in medical history such as male gender, younger age of dislocation, an increasing number of dislocations, contact sports, and manual work or epilepsy may increase the recurrence rate of instability.In physical examination, positive bony apprehension test, catching and crepitations in shoulder movement may suggest osseous deficiency.

Milk and dairy product consumption in patients with inflammatory bowel disease: Helpful or harmful to bone mineral density?

Objectives: Limiting the consumption of milk and dairy products (DPs) constitutes a risk factor for osteoporosis in patients with inflammatory bowel disease (IBD). The aim of this study was to evaluate bone mineral density (BMD) and the frequency of osteopenia and osteoporosis in patients with IBD. We also investigated the correlation between BMD and consumption of milk and DPs, as well as with calcium, phosphate, and parathyroid hormone (PTH) and 25-hydroxyvitamin D [25(OH)D] serum concentration levels.

Analysis of the tumor necrosis factor superfamily member 11 gene polymorphism with bone mineral density and bone fracture frequency in patients with postmenopausal osteoporosis.

Purpose: We aimed to examine the polymorphism of the promoter and exon 5 of the TNFSF11 gene and their impact on bone mineral density (BMD) and the frequency of bone fractures. TNFSF11 encodes the receptor activator of the NF-kB ligand (RANKL), a key regulator of bone metabolism and osteoporosis drug targets. BMD is an essential measure in diagnosing osteoporosis and assessing the risk of fractures.

Frizzled 7 and PIP2 binding by syntenin PDZ2 domain supports Frizzled 7 trafficking and signalling.

PDZ domain-containing proteins work as intracellular scaffolds to control spatio-temporal aspects of cell signalling. This function is supported by the ability of their PDZ domains to bind other proteins such as receptors, but also phosphoinositide lipids important for membrane trafficking. Here we report a crystal structure of the syntenin PDZ tandem in complex with the carboxy-terminal fragment of Frizzled 7 and phosphatidylinositol 4,5-bisphosphate (PIP2).

Phosphoinositides and PDZ domain scaffolds.

The discovery that PSD-95/Discs large/ZO-1 (PDZ) domains can function as lipid-binding modules, in particular interacting with phosphoinositides (PIs), was made more than 10 years ago (Mol Cell 9(6): 1215-1225, 2002). Confirmatory studies and a series of functional follow-ups established PDZ domains as dual specificity modules displaying both peptide and lipid binding, and prompted a rethinking of the mode of action of PDZ domains in the control of cell signaling. In this chapter, after introducing PDZ domains, PIs and methods for studying protein-lipid interactions, we focus on (i) the prevalence and the specificity of PDZ-PIs interactions, (ii) the molecular determinants of PDZ-PIs interactions, (iii) the integration of lipid and peptide binding by PDZ domains, (iv) the common features of PIs interacting PDZ domains and (v) the regulation and functional significance of PDZ-PIs interactions.

Prognostic factors in patients surgically treated after hip fracture.

Introduction: By the impact of demographic changes and as the result of the 'incorrect' lifestyles pursued in developed societies, osteoporosis has become a serious social problem. Hip fracture is the most serious complication of osteoporosis and is associated with high mortality rates or permanent health impairment. The goal of this study was an evaluation of the impact of selected socio-economic factors and of the time period from fracture to surgical intervention on the patient's prognosis.

Prevalence, specificity and determinants of lipid-interacting PDZ domains from an in-cell screen and in vitro binding experiments.

Background: PDZ domains are highly abundant protein-protein interaction modules involved in the wiring of protein networks. Emerging evidence indicates that some PDZ domains also interact with phosphoinositides (PtdInsPs), important regulators of cell polarization and signaling. Yet our knowledge on the prevalence, specificity, affinity, and molecular determinants of PDZ-PtdInsPs interactions and on their impact on PDZ-protein interactions is very limited.

Vitamin D receptor gene polymorphisms, bone mineral density and fractures in postmenopausal women with osteoporosis.

The goal of the study was to investigate the possibility of an association between polymorphisms and single alleles of BsmI, ApaI, TaqI of the vitamin D receptor (VDR) gene with bone mineral density (BMD) and prevalence of vertebral/non-vertebral fractures in a group of postmenopausal Polish women with osteoporosis. The study group comprised of 501 postmenopausal females with osteoporosis (mean age 66.4 ± 8.

Extensions of PSD-95/discs large/ZO-1 (PDZ) domains influence lipid binding and membrane targeting of syntenin-1.

Syntenin-1 is a PDZ protein involved in receptor recycling and clustering. Its two PDZ domains interact with various receptors and phosphoinositides, and are flanked by N- and C-terminal regions. Here, we report the identification of an autoinhibitory peptide stretch in the N-terminus that might be regulated by phosphorylation.

[The role of hormonal therapy in osteoporosis].

In developed societies, the post-menopausal period covers approximately one third of a woman's life. The deficit of oestrogens observed during the post-menopausal period significantly affects the course of many metabolic processes, causing a number of diseases and in consequence diminishing quality of life. Among others, bones belong to oestrogen-dependent tissues.

Cooperative phosphoinositide and peptide binding by PSD-95/discs large/ZO-1 (PDZ) domain of polychaetoid, Drosophila zonulin.

PDZ domains are well known protein-protein interaction modules that, as part of multidomain proteins, assemble molecular complexes. Some PDZ domains have been reported to interact with membrane lipids, in particular phosphatidylinositol phosphates, but few studies have been aimed at elucidating the prevalence or the molecular details of such interactions. We screened 46 Drosophila PDZ domains for phosphoinositide-dependent cellular localization and discovered that the second PDZ domain of polychaetoid (Pyd PDZ2) interacts with phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P(2)) at the plasma membrane.

The role of hormonal therapy in osteoporosis.

In developed societies, the post-menopausal period covers approximately one third of a woman's life. The deficit of oestrogens observed during the post-menopausal period significantly affects the course of many metabolic processes, causing a number of diseases and in consequence diminishing quality of life. Among others, bones belong to oestrogen-dependent tissues.

A discussion of the intervention thresholds in osteoporosis treatment in Poland.

Introduction: Epidemiological prognoses regarding the global spread of post-menopausal osteoporosis can prove somewhat nebulous. But it is clear that low-energy fractures and their consequences will become an increasingly serious health problem. Therefore it is crucial to implement prognostic procedures which could more effectively predict the incidence of osteoporosis and its complications.

Correlation of vitamin D receptor gene (VDR) polymorphism with osteoporotic changes in Polish postmenopausal women.

Objective: Recently the significance of genetic traits, influencing hormonal and environmental factors, in susceptibility to osteopenia and osteoporosis development has been indicated. Much attention to the polymorphic variants of vitamin D receptor (VDR) gene was paid. The restriction polymorphisms in VDR gene could be involved in the modulation of vitamin D action and modulate the level of bone mineral density (BMD) and the risk to develop osteopenia and osteoporosis.

[Senile osteoporosis].

Osteoporosis is a skeletal disease characterized by the increased risk of fractures, decreased bone mass and bone quality. The number of patients suffering from osteoporosis still increase due to the extension of the lifespan in the developed countries. The low-energy hip fractures are the most severe complications of the disease, lethal in some cases.

Association analysis of the polymorphisms of the VDR gene with bone mineral density and the occurrence of fractures.

Associations of the FokI, BsmI, ApaI, and TaqI polymorphisms of the vitamin D receptor (VDR) gene with the bone mineral density (BMD) of the lumbar part of the spinal column (BMD LS) and the neck of the femur (BMD FN), and with the occurrence of fractures, were studied using the polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analysis on DNA isolated from peripheral blood of 239 women and 40 men from the region of western Poland. Three polymorphisms of the 3' end of the VDR gene (BsmI, ApaI, TaqI) indicated a strong linkage disequilibrium. Association analysis of the VDR gene FokI polymorphism with BMD LS showed a dose effect of allele f.

The prognostic value of quality of life parameters in patients recovering from osteoporotic fractures of the proximal femur.

Background. Improving the quality of life is the aim of treatment in elderly patients with hip fracture. Different outcomes are often achieved using similar therapy methods.

[Quality of life in patients with hip bone fractures].

Unlabelled: The aim of the study was to evaluate quality of life in patients who received surgical treatment of hip fracture.

Material And Methods: Fifty patients (mean age: 77,5) including 37 women and 13 men participated in the study. All patients filled in a questionnaire constructed specially for the study.

Polymorphism of VDR gene--the most effective molecular marker of osteoporotic bone fractures risk within postmenopausal women from Wielkopolska region of Poland.

The major public health problem which will arise is a frequency of osteoporosis. The first manifestations of this disease are often bone fractures. Identification and evaluation of individual bone fracture risk will be the most effective way of solving the problem.