Abstract:
:Strontium ranelate is composed of an organic moiety (ranelic acid) and of two atoms of stable non-radioactive strontium. In vitro, strontium ranelate increases collagen and non-collagenic proteins synthesis by mature osteoblast enriched cells. The effects of strontium ranelate on bone formation were confirmed as strontium ranelate enhanced pre-osteoblastic cells replication. The stimulation by strontium ranelate of the replication of osteoprogenitor cells and collagen as well as non-collagenic protein synthesis in osteoblasts provides substantial evidence to categorise SR ranelate as a bone forming agent. In the mouse calvaria culture system, SR ranelate induces a dose-dependent inhibition of labelled calcium release. The inhibitory effects of SR ranelate on bone resorption were close to those of salmon calcitonin. In the isolated rat osteoclast assay, a pre-incubation of bone slices with SR ranelate induced a dose-dependent inhibition of the bone resorbing activity of a treated rat osteoclast. SR ranelate also dose-dependently inhibited, in a chicken bone marrow culture, the expression of both CA II and the alpha-subunit of the vitronectin receptor. These effects showing that SR ranelate significantly affects bone resorption due to direct and/or matrix-mediated inhibition of osteoclast activity and also inhibits osteoclasts differentiation are compatible with the profile of an anti-resorptive drug. In normal rats, administration of SR ranelate induces an improvement in the mechanical properties of the humerus and/or the lumbar vertebra associated with a commensurate increase in bone dimension, shaft and volume. This was not related to any change in the stiffness, suggesting the absence of a mineralisation defect. After oral administration of SR ranelate in humans, the absolute bio-availability of SR ranelate is 27 % after a dose of 2g is given as sachets. The simultaneous intake of SR ranelate and calcium remarkably reduces the bio-availability of SR. SR ranelate was administered in 160 early postmenopausal women, in a 24-month, double-blind, placebo-controlled, prospective randomized study. Daily oral dose of 125 mg, 500 mg, 1 g of SR ranelate were compared to a placebo. At the conclusion of the study, the percent variation of lumbar adjusted BMD from baseline was significantly different in the group receiving 1 g/day of SR as compared to placebo (+ 1.41 % versus 0.98 % respectively). Increase in total hip and neck BMD averages respectively 3.2 % and 2.5 %. SR ranelate does not induce any significant adverse reaction compared to those observed in women receiving a placebo for the same duration. In a phase II study, the effect of SR ranelate in postmenopausal women with vertebral osteoporotic fractures were assessed during a double-blind, placebo-controlled trial. SR ranelate (500 mg, 1 g, 2 g per day) or placebo were given to 353 Caucasian women with prevalent osteoporosis. At the conclusion of this two-year study, the annual increase in lumbar adjusted BMD of the group receiving 2 g of SR ranelate was + 2.97 %. This result was significantly different as compared to placebo. A significant decrease in pyridinium crosslinks (NTX) and an increase in bone specific alkaline phosphatase were evident after 3 and 6 months of treatment. During the second year of treatment, the dose of 2 g was associated with a 4 % reduction in the number of patient experiencing a new vertebral deformity. Bone histomorphometry showed no mineralisation defects. The same percentage of withdrawal following an adverse effect was observed for patients receiving placebo and for those receiving 2 g of strontium ranelate. Currently, strontium ranelate is further investigated in a large Phase III program that includes two extensive trials for the treatment of severe osteoporosis, one assessing SR ranelate effects on the risk of vertebral fractures (SOTI) and one evaluating the effects of SR ranelate on peripheral (non spinal) fractures (TROPOS). The primary analysis of the SOTI study, evaluating the effect of 2 g of strontium ranelate on vertebral fracture rates are expected to be released during the summer 2002.
journal_name
Curr Pharm Desjournal_title
Current pharmaceutical designauthors
Reginster JYdoi
10.2174/1381612023393639subject
Has Abstractpub_date
2002-01-01 00:00:00pages
1907-16issue
21eissn
1381-6128issn
1873-4286journal_volume
8pub_type
杂志文章,评审abstract::Interest in opioid drugs like morphine, as the oldest and most potent pain-killing agents known, has been maintained through the years. One of the most frequent chronic pain sensations people experience is associated with pathological conditions of the musculoskeletal system. Chronic musculoskeletal pain is a major he...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/13816128113199990363
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abstract::Phytoestrogens are plant-derived compounds with estrogen-like activities. Certain foods such as soy-derived products are known to have high levels of phytoestrogens, and about 25% of commercial infant formulas used in the United States are soy-based. One of the most important phytoestrogens is the isoflavone genistein...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612043383683
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journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161211797904172
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abstract::Active pharmaceutical ingredients (APIs) can exist in different polymorphic forms as well as in amorphous state. Polymorphic and amorphous forms of APIs can differ in physicochemical properties which in turn can significantly influence their therapeutic safety and effectiveness of the treatment. This review focuses on...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612822666160804100036
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abstract::Angiogenesis is regulated by stimulators and inhibitors and involve multiple biological processes including endothelial cell proliferation, migration, cell-cell and cell-matrix adhesion, assembly into tube structures as well as apoptosis. Designing and developing peptides for therapeutic application to inhibit angioge...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/138161207781039715
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abstract::Neuromuscular blocking agents are the leading drugs responsible for immediate hypersensitivity reactions during anaesthesia. Most hypersensitivity reactions represent IgE-mediated allergic reactions. Their incidence is estimated to be between 1 in 3,000 to 1 in 110,000 general anaesthetics. However striking variations...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161208786369704
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abstract::The state-of-the-art in the investigation of drugs release from Silica-based ordered Mesoporous Materials (SMMs) is reviewed. First, the SMM systems used like host matrixes are described. Then, the model drugs studied until now, including their pharmacological action, structure and the mesoporous matrix employed for e...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612822666151106121419
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journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/13816128113196660060
更新日期:2014-01-01 00:00:00
abstract:BACKGROUND:Fragile X syndrome (FXS) is the most common form of monogenic hereditary cognitive impairment, including intellectual disability, autism, hyperactivity, and epilepsy. METHODS:This article reviews the literature pertaining to the role of synaptic dysfunction in FXS. RESULTS:In FXS, synaptic dysfunction alte...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612825666191102165206
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journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161212802083716
更新日期:2012-01-01 00:00:00
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journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
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更新日期:2013-01-01 00:00:00
abstract:BACKGROUND:Neuroanatomical abnormalities, including cingulate cortex volume abnormalities, are a common feature in psychosis. However, the extent to which these are related to a vulnerability to psychosis, as opposed to the disorder per se, is less certain. AIM UND HYPOTHESES: The aim of the present study is to compare...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/138161212799316316
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abstract::Arterial thromboembolism is a sudden obstruction of arterial blood flow caused by dislodgment of a blood clot from the site of its formation. Atrial fibrillation (AF) is the most common cardiac arrhythmia and a major risk factor for arterial thromboembolism in clinical practice. Most of AF-related arterial thromboembo...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161210793563400
更新日期:2010-01-01 00:00:00
abstract::Stroke is a leading cause of death and disability worldwide. Conventional treatment has a limitation of very narrow therapeutic time window and its devastating nature necessitate a novel regenerative approach. Transplanted stem cells resulted in functional recovery through multiple mechanisms including neuroprotection...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612824666180604111806
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abstract::Two morphological features may be seen as a main result of the cardiovascular cell damage caused by cigarette smoking: myocardial cell necrosis and smoke cardiomyopathy that, however, can lead to cell necrosis in case of chronic prolonged exposure to tobacco smoke. Both these pathological patterns recognise hypoxia as...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161208784746699
更新日期:2008-01-01 00:00:00
abstract::The typical way of judging about either the efficacy of a new treatment or, on the contrary, the damage of a pollutant agent is through a test of hypothesis having its ineffectiveness as null hypothesis. This is the typical operational field of Kolmogorov's statistical framework where wastes of data (for instance non ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161207780765891
更新日期:2007-01-01 00:00:00
abstract::Aneuploidy is a pathological condition that affects 35% of human spontaneous abortions and 0.3% of livebirths. In spite of the increasing knowledge about molecular mechanisms of meiosis and chromosome segregation, maternal age remains the only ascertained aetiological factor. Genetically modified mouse models have bee...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161206776389859
更新日期:2006-01-01 00:00:00
abstract:BACKGROUND:From the evidence of failed injection-based growth factor therapies, it has been proposed that a naturally triggered uninterrupted blood circulation of the growth factors would be superior. OBJECTIVE:We seek to stimulate discussions and more research about the possibility of using the already available grow...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612826666201019104201
更新日期:2020-10-18 00:00:00
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journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
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更新日期:2009-01-01 00:00:00
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journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
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更新日期:2004-01-01 00:00:00
abstract:BACKGROUND:Erectile dysfunction (ED) is an evolving health problem in the aging male population. Chronic low-grade inflammation is a critical component of ED pathogenesis and a probable intermediate stage of endothelial dysfunction, especially in metabolic diseases, with the inclusion of obesity, metabolic syndrome, an...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
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journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612003400551
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abstract::The derangement of the cardiac energy substrate metabolism plays a key role in the pathogenesis of heart failure. The utilization of non-carbohydrate substrates, such as fatty acids, is the predominant metabolic pathway in the normal heart, because this provides the highest energy yield per molecule of substrate metab...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
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更新日期:2011-12-01 00:00:00
abstract::Dioxygen (O2) is an exogenously supplied gas with a number of properties that make it valuable as a biological source of energy and as a result much of life has become dependent on this molecule. Nitric oxide (NO), carbon dioxide (CO) and hydrogen sulfide (H2S) are small molecules that are sometimes in a gaseous state...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
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更新日期:2007-01-01 00:00:00
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journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
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更新日期:2004-01-01 00:00:00
abstract:BACKGROUND:Vitamin D exerts multiple pleiotropic effects beyond its role in calcium-phosphate metabolism. Growing evidence suggests an association between hypovitaminosis D and sleep disorders, thus increasing the interest in the role of this vitamin in the regulatory mechanisms of the sleep-wake cycle. OBJECTIVE:The ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612826666200310145935
更新日期:2020-01-01 00:00:00
abstract:: ...
journal_title:Current pharmaceutical design
pub_type: 社论
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更新日期:2018-01-01 00:00:00
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journal_title:Current pharmaceutical design
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更新日期:2007-01-01 00:00:00
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journal_title:Current pharmaceutical design
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更新日期:2004-01-01 00:00:00
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journal_title:Current pharmaceutical design
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