Abstract:
:Systematic studies of autosomal dominant osteopetrosis (ADO) were followed by the identification of underlying mutations giving unique possibilities to perform translational studies. What was previously designated ADO1 turned out to be a high bone mass phenotype caused by a missense mutation in the first propeller of LRP5, a region of importance for binding inhibitory proteins. Thereby, ADO1 cannot be regarded as a classical form of osteopetrosis but must now be considered a disease of LRP5 activation. ADO (Albers-Schönberg disease, or previously ADO2) is characterized by increased number of osteoclasts and a defect in the chloride transport system (ClC-7) of importance for acidification of the resorption lacuna (a form of Chloride Channel 7 Deficiency Osteopetrosis). Ex vivo studies of osteoclasts from ADO have shown that cells do form normally but have reduced resorption capacity and an expanded life span. Bone formation seems normal despite decreased osteoclast function. Uncoupling of formation from resorption makes ADO of interest for new strategies for treatment of osteoporosis. Recent studies have integrated bone metabolism in whole-body energy homeostasis. Patients with ADO may have decreased insulin levels indicating importance beyond bone metabolism. There seems to be a paradigm shift in the treatment of osteoporosis. Targeting ClC-7 might introduce a new principle of dual action. Drugs affecting ClC-7 could be antiresorptive, still allowing ongoing bone formation. Inversely, drugs affecting the inhibitory site of LRP5 might stimulate bone formation and inhibit resorption. Thereby, these studies have highlighted several intriguing treatment possibilities, employing novel modes of action, which could provide benefits to the treatment of osteoporosis.
journal_name
Eur J Endocrinoljournal_title
European journal of endocrinologyauthors
Bollerslev J,Henriksen K,Nielsen MF,Brixen K,Van Hul Wdoi
10.1530/EJE-13-0136subject
Has Abstractpub_date
2013-07-13 00:00:00pages
R39-57issue
2eissn
0804-4643issn
1479-683Xpii
EJE-13-0136journal_volume
169pub_type
杂志文章,评审abstract:OBJECTIVE:GH deficiency (GHD) and glucocorticoid excess are associated with increased risk of fragility fractures. We aimed to evaluate whether the prevalence of vertebral fractures may be influenced by glucocorticoid over-replacement in hypopituitary males with GHD. DESIGN:Cross-sectional study. METHODS:Fifty-one ad...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/EJE-10-0125
更新日期:2010-07-01 00:00:00
abstract::Ionomycin, which mobilizes Ca2+, and phorbol 12-myristate 13-acetate (PMA), which activates protein kinase C (PKC), were used to compare the effects/interactions of Ca2+ and PKC on luteinizing hormone (LH) secretion from pituitaries of intact male and acutely ovariectomized (72 h) rats. Quartered pituitaries from dono...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/eje.0.1300151
更新日期:1994-02-01 00:00:00
abstract:INTRODUCTION:The fetus is most vulnerable to severe iodine deficiency and hypothyroidism during pregnancy. The effects of mild iodine deficiency and subclinical hypothyroidism are poorly known. The present study assesses the association between thyroid hormones (TH)s and urinary iodine concentration (UIC) in healthy pr...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/EJE-08-0716
更新日期:2009-03-01 00:00:00
abstract:OBJECTIVE:IGF1 is essential for human growth and mediates its effects through the type 1 IGF receptor (IGF1R). Our objective was to determine the frequency of certain previously reported IGF1R gene variants in the normal population and their effect on stature. DESIGN:A cross-sectional study was conducted in a populati...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/EJE-12-0565
更新日期:2012-12-01 00:00:00
abstract:OBJECTIVE:Paraoxonase-1 (PON-1), which has PON and arylesterase activities, is a high-density lipoprotein (HDL)-bound antioxidant enzyme that inhibits atherosclerosis. Diabetes has been shown to have an impact on oxidative stress. The effect of metabolic syndrome (MetS) on oxidative stress and PON-1 has been shown befo...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/EJE-09-0732
更新日期:2010-03-01 00:00:00
abstract::Skeletal anabolic agents enhance bone formation, which is determined by the number and function of osteoblasts. Signals that influence the differentiation and function of cells of the osteoblast lineage play a role in the mechanism of action of anabolic agents in the skeleton. Wnts induce the differentiation of mesenc...
journal_title:European journal of endocrinology
pub_type: 杂志文章,评审
doi:10.1530/EJE-17-0920
更新日期:2018-02-01 00:00:00
abstract:OBJECTIVE:A polymorphism near the promoter region of the IGF-I gene has been associated with serum IGF-I levels, body height and birth weight. In this study, we investigated whether this polymorphism is associated with body composition in young healthy subjects in two cohorts of different generations. DESIGN:Observati...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/eje.1.02101
更新日期:2006-03-01 00:00:00
abstract:OBJECTIVE AND DESIGN:Based on our clinical experience with combined gene therapy of glioblastoma, we developed a retroviral vector expressing two therapeutic genes (i.e. thymidine kinase of herpes simplex virus, HSV-TK, and interleukin-2, IL-2) and evaluated its efficiency in vitro and in vivo. METHODS:Expression of t...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/eje.0.1480073
更新日期:2003-01-01 00:00:00
abstract::For patients with neuroendocrine tumours (NETs) of the gastrointestinal tract and pancreas (GEP) (GEP-NETs), excellent care should ideally be provided by a multidisciplinary team of skilled health care professionals. In these patients, a combination of nuclear medicine imaging and conventional radiological imaging tec...
journal_title:European journal of endocrinology
pub_type: 杂志文章,评审
doi:10.1530/EJE-14-0077
更新日期:2014-04-10 00:00:00
abstract:OBJECTIVE:To study the contribution of a normal intake of nutrients to the variability of serum leptin concentrations in persons with type 1 diabetes mellitus. DESIGN:We studied the relation between serum leptin and nutrient intake in a cross-sectional study. METHODS:Serum leptin measured by radioimmunoassay, nutriti...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/eje.0.1420263
更新日期:2000-03-01 00:00:00
abstract:BACKGROUND:We examined the hypothesis that high FGF-23 levels early after transplantation contribute to the onset of hypophosphatemia, independently of parathyroid hormone (PTH) and other factors regulating phosphate metabolism. METHODS:We measured serum phosphate levels (sPi), renal tubular reabsorption of Pi (TmPi/G...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/EJE-10-1150
更新日期:2011-05-01 00:00:00
abstract:OBJECTIVE:Our purpose was to study the sex steroid-mediated changes in serum insulin and lipid concentrations in boys during puberty. DESIGN AND METHODS:We treated boys with constitutional delay of puberty either with testosterone plus placebo or with testosterone plus an aromatase inhibitor, letrozole, which inhibits...
journal_title:European journal of endocrinology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1530/eje.0.1460339
更新日期:2002-03-01 00:00:00
abstract::Acromegaly is associated with high morbidity and elevated mortality when not adequately treated. Surgery is the first-line treatment for most patients as it is the only one that can lead to immediate cure. In patients who are not cured by surgery, treatment is currently based on a trial-and-error approach. First-gener...
journal_title:European journal of endocrinology
pub_type: 杂志文章,评审
doi:10.1530/EJE-17-1006
更新日期:2018-03-01 00:00:00
abstract::Iodine incorporation into thyroglobulin is dependent on the activities of both thyroperoxidase (TPO) and thyroid dual oxidase 2 (DuOx2). Although TPO expression is decreased in some thyroid nodular lesions, DuOx1 and 2 mRNA expressions are maintained, but DuOx H2O2-generating activity has never been evaluated in such ...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/EJE-07-0602
更新日期:2008-02-01 00:00:00
abstract:OBJECTIVE:Amine precursor uptake and decarboxylation is a classical feature of gastroenteropancreatic (GEP) neuroendocrine tumors (NET). Production of catecholamines was studied in GEP NET and non-NET patients. DESIGN:A cross-sectional study was undertaken. METHODS:We studied catecholamine and metabolite secretion in...
journal_title:European journal of endocrinology
pub_type: 临床试验,杂志文章
doi:10.1530/eje.0.1400434
更新日期:1999-05-01 00:00:00
abstract:OBJECTIVE:To evaluate the impact of long-term, non-suppressive levothyroxine (L-T(4)) treatment on quantitative ultrasonometry in women. DESIGN:This was a case-control study. SUBJECTS AND METHODS:Altogether 667 women (mean age+/-s.d., 49.5+/-13.1 years) were studied. Of these, 156 (23%) had non-toxic goitre or hypoth...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/eje.0.1420445
更新日期:2000-05-01 00:00:00
abstract::The p16INK4A and p15INK4B genes on chromosome 9p21 encode the p16 and p15 inhibitors of cyclin D/cyclin-dependent kinase 4 complexes respectively. Mutations and deletions of the p16INK4A gene have been found in melanomas and many other types of tumors. To assess the role of the p16INK4A and p15NK4B genes in tumorigene...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/eje.0.1360074
更新日期:1997-01-01 00:00:00
abstract:OBJECTIVE:This study evaluated the short- and long-term cardiovascular- and cancer-related morbidities during cross-sex hormone therapy in a large sample of trans persons. SUBJECTS AND METHODS:A specialist center cross-sectional study compared 214 trans women (male-to-female transsexual persons) and 138 trans men (fem...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/EJE-13-0493
更新日期:2013-09-13 00:00:00
abstract:OBJECTIVE:Neck and thorax single photon emission computed tomography with computed tomography (SPECT-CT) improves the reliability of postablation (131)I whole-body scan (WBS) for differentiated thyroid cancer (DTC). The aim of this study was to assess the prognostic value for persistent or recurrent disease of postabla...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/EJE-11-0156
更新日期:2011-06-01 00:00:00
abstract:OBJECTIVE:Secreted protein acidic and rich in cysteine (SPARC) also known as BM-40 which has been studied in various pathological conditions, has recently been suggested as a key player in the pathology of obesity and type 2 diabetes mellitus (T2DM). However, there are few studies on putative pathophysiologic roles of ...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/EJE-11-0131
更新日期:2011-10-01 00:00:00
abstract::The experimental model of chronic inhibition of nitric oxide (NO) production has proven to be a useful tool to study cardiovascular and renal lesions produced by this type of hypertension, which are similar to those found in human hypertension. It also offers a unique opportunity to study the interaction of NO with th...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/eje.1.02314
更新日期:2007-01-01 00:00:00
abstract:BACKGROUND:Ghrelin stimulates GH secretion and regulates energy and glucose metabolism. The two circulating isoforms, acyl (AG) and des-acyl (DAG) ghrelin, have distinct metabolic effects and are under active investigation for their therapeutic potentials. However, there is only limited data on the pharmacokinetics of ...
journal_title:European journal of endocrinology
pub_type: 杂志文章,随机对照试验
doi:10.1530/EJE-13-0072
更新日期:2013-05-02 00:00:00
abstract::Activating mutations of G proteins, which are membrane signal transducers, have been associated recently with the development of various endocrine neoplasms. Mutations of two highly conserved codons, Arg201 and Gln227, in the alpha-subunit of the Gs protein, the adenylyl cyclase-stimulating protein, were first describ...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/eje.0.1330166
更新日期:1995-08-01 00:00:00
abstract::The present study focuses on the pathogenesis of increased frequency of large-vessel disease in diabetes. The diabetic arterial wall displays characteristic alterations of the extracellular matrix secreted by arterial smooth-muscle cells. The effects of insulin and growth hormone on the synthesis of sulphate-labelled ...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/eje.0.1340326
更新日期:1996-03-01 00:00:00
abstract:OBJECTIVES:The aim of the present study was to determine vascular endothelial growth factor (VEGF), prostaglandin E(2) (PGE(2)) and active renin levels in patients with hormonally active adrenal tumours. DESIGN:The study was comprised of 16 patients with primary aldosteronism, 13 patients with active Cushing's syndrom...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/eje.0.1500345
更新日期:2004-03-01 00:00:00
abstract:OBJECTIVES:The purpose of this population-based prospective cohort study was to examine the effect of hormone therapy (HT) on incidence of diabetes mellitus (DM). DESIGN AND METHODS:Eight thousand four hundred and eighty-three DM-free post-menopausal women aged 52-62 from the population-based Kuopio osteoporosis risk ...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/EJE-09-0151
更新日期:2009-06-01 00:00:00
abstract::This manuscript provides guidance on the management of thyroid dysfunction during the COVID-19 pandemic. Autoimmune thyroid diseases are not linked to increased risks of COVID-19. Uncontrolled thyrotoxicosis may result in more severe complications from SARS-CoV-2 infection, including thyroid storm. The management of p...
journal_title:European journal of endocrinology
pub_type: 杂志文章,评审
doi:10.1530/EJE-20-0445
更新日期:2020-07-01 00:00:00
abstract:BACKGROUND:Sleep behavior is changing toward shorter sleep duration and a later chronotype. It results in a sleep debt that is acquitted on work-free days, inducing a small but recurrent sleep misalignment each week, referred to as "social jetlag". These sleep habits could affect health through misalignment with circad...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/EJE-16-0188
更新日期:2016-11-01 00:00:00
abstract:OBJECTIVE:To compare the presentation and clinical course of Graves' disease (GD) in two pediatric populations consisting of 28 patients with Down's syndrome (DS) and 109 controls without DS respectively. DESIGN AND METHODS:The evolution over time of GD was determined in both groups according to the clinical changes a...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/EJE-09-0751
更新日期:2010-03-01 00:00:00
abstract::Objective To explore whether gestational prolactin and breast increase are markers of metabolic health in pregnancy and on long-term, in PCOS. Design Follow-up study. Women with PCOS, according to the Rotterdam criteria (n = 239), former participants of the randomized controlled trial (RCT) PregMet were invited, 131 p...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/EJE-19-0002
更新日期:2019-06-01 00:00:00