阿仑膦酸钠/胆骨化醇(Alendronate Sodium/Cholecalciferol) - 药物靶点：VDR_在研适应症：绝经期后骨质疏松，骨质疏松症_专利_临床

概要

基本信息

药物类型

小分子化药

别名

Adrovance、Alendronate Sodium Trihydrate/Colecalciferol、Alendronate Sodium/Colecalciferol

+ [10]

靶点

VDR

作用机制

VDR激动剂(维生素D受体激动剂)、破骨细胞抑制剂

治疗领域

内分泌与代谢疾病皮肤和肌肉骨骼疾病

在研适应症

绝经期后骨质疏松骨质疏松症

非在研适应症

维生素D缺乏症

原研机构

Merck Sharp & Dohme Corp.

在研机构

Organon NV

Organon & Co.南京九霄药业有限公司

+ [2]

非在研机构

Merck Sharp & Dohme Corp.

最高研发阶段批准上市

首次获批日期

美国 (2005-04-07),

骨质疏松症

最高研发阶段(中国)批准上市

特殊审评-

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结构

分子式C31H63NNaO11P2

InChIKeyZBOIUMYEYAMMKJ-FYLNQELCSA-N

CAS号871265-92-8

关联

16

项与阿仑膦酸钠/胆骨化醇相关的临床试验

EUCTR2019-003101-97-ES / Unknown status临床4期

An unicentric, open, randomized and crossover clinical trial to evaluate vitamin D supplementation effect of colecalciferol versus calcidiol in mineral metabolism in hemodialisis patients.

开始日期2020-02-18

申办/合作机构-

NCT02132026 / Completed临床2期IIT

SALTIRE II: Bisphosphonates and RANKL Inhibition in Aortic Stenosis

Aortic stenosis is a condition whereby one of the heart valves (aortic valve) becomes narrowed, due to calcium deposition, over time. This can lead to chest pain, heart failure and sudden death. It is the commonest valve disease requiring surgery in the developed world and as the population becomes increasingly older, it is predicted that the prevalence of aortic stenosis will double in the next 20 years. Currently the only treatment is replacement of the aortic valve. Whilst this is excellent treatment, not everyone is suitable for it.
The primary objective of our study is to determine whether 2 drugs used in the treatment of osteoporosis (a condition of bone thinning) can halt/retard the progression of aortic stenosis. This is on the basis that studies have suggested that altered regulation of calcium metabolism may be an important mechanism perpetuating the disease. Both drugs work by reducing calcium release into the bloodstream from bones and therefore calcification of the aortic valve.
150 patients will therefore be randomly allocated to either of the trial drugs which are denosumab,the bisphosphonate (alendronic acid), or a placebo.
Positron Emission Tomography (PET) scanning is a technique where biochemically active molecules are injected and are taken up at sites of ongoing calcification activity where they emit radiation and can be detected by the PET scanner. We have previously shown that this technique can demonstrate areas of newly developing calcification on an aortic valve.
We therefore propose that patients receiving bisphosphonates or denosumab will have reduced evidence of active calcification and slower progression of their disease at two years as assessed by Echocardiography (ultrasound) and a change in their calcium score (quantity of calcium on the aortic valve measured using Computed Tomography [CT] ).
The data from this study will then be used to design a larger trial.

开始日期2014-11-12

申办/合作机构

The University of Edinburgh

[+2]

NCT00692913 / Completed临床3期

A Phase III (Phase V Program), Open-Label, Randomized, Referred-Care-Controlled, Clinical Trial to Evaluate the Efficacy and Safety of MK -0217A/Alendronate Sodium-70 mg/Vitamin D3 5600 I.U. Combination Tablet on Vitamin D Inadequacy in the Treatment of Osteoporosis in Postmenopausal Women

A study designed to see if the study drug will increase blood levels of vitamin D, bone mineral density (BMD), improve biochemical markers of bone turnover, and reduce the number of falls as compared to women receiving standard care for osteoporosis.

开始日期2008-06-01

申办/合作机构

Organon & Co.

100 项与阿仑膦酸钠/胆骨化醇相关的临床结果

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100 项与阿仑膦酸钠/胆骨化醇相关的转化医学

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100 项与阿仑膦酸钠/胆骨化醇相关的专利（医药）

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5

项与阿仑膦酸钠/胆骨化醇相关的文献（医药）

2016-04-15·Phytomedicine2区 · 医学

NF-κB pathway inhibition by anthrocyclic glycoside aloin is key event in preventing osteoclastogenesis in RAW264.7 cells

2区 · 医学

Article

作者: Pengjam, Yutthana ; Madhyastha, Harishkumar ; Madhyastha, Radha ; Yamaguchi, Yuya ; Nakajima, Yuichi ; Maruyama, Masugi

BACKGROUND:

Osteoporosis is a bone pathology leading to increased fracture risk and challenging the quality of life. As current treatments can exhibit deleterious side effects, the use of phyto-compounds with therapeutic and preventive activities against orthopaedic related problems represents a promising alternative.

PURPOSE:

We investigated the effect of aloin, an anthrocyclic compound, on inhibition of osteoclastogenesis using receptor of the nuclear factor κB (NF-κB) ligand (RANKL)-induced RAW264.7 macrophage cells.

STUDY DESIGN/METHODS:

The inhibitory effect of aloin on in vitro osteoclastogenesis was evaluated by reduction in tartrate-resistant acid phosphatase (TRAP) content and expression levels of osteoclast-specific gene, cathepsin K. Multinuclear formation of osteoclast was assessed with haematoxylin and eosin staining. F4/80 content the marker of the murine monocyte/macrophage cells, was evaluated by immunocytochemistry. The underlining mechanisms were assessed by Western blots and EMSA. Effect of aloin on generation of intracellular reactive oxygen species (ROS) was estimated by dichlorofluorescein diacetate (DCFH-DA). Bone degradation effect was evaluated by bone pit assay. The bone pit culture supernatant was studied by Fluorescein assay.

RESULTS:

We demonstrated that aloin reduced TRAP content and levels of osteoclast-specific gene and protein, cathepsin K. Treatment with aloin (0.75 µM) prevented multinuclear formation (haematoxylin and eosin staining), reduced intracellular TRAP content (TRAP Staining) and increased F4/80 content (F4/80 immunohistochemistry) in RANKL (20 ng/ml) treated RAW cells. Treatment of the RAW cells with aloin suppressed RANKL-induced NF-κB pathway components like IKKα, IKKβ, Phospho.IKK α/β, NF-κB-p65, Phospho NF-κB-p65 and IκBα. EMSA studies showed aloin dose dependently reduced DNA binding activity of NF-κB. Additionally, in vitro bone pit assay revealed that aloin prevented bone degradation and also decreased the fluorescence content in cells, thus confirming the role of aloin in inhibition of osteoclastogenesis .

CONCLUSION:

Collectively, this study identifies aloin as a potent inhibitor of osteoclastogenesis and bone resorption. The action of aloin was in par with alendronate sodium trihydrate and may provide evidence for its therapeutic potential to treat diseases involving abnormal bone lysis.

2008-03-01·Current Medical Research and Opinion4区 · 医学

Cost-effectiveness of a fixed dose combination of alendronate and cholecalciferol in the treatment and prevention of osteoporosis in the United Kingdom and The Netherlands

4区 · 医学

Article

作者: Jansen, Jeroen P. ; Gaugris, Sabine ; Bergman, Gert ; Sen, Shuvayu S.

OBJECTIVE:

To evaluate the cost-effectiveness of a fixed dose combination of alendronate 70 mg and cholecalciferol 2800 IU (alendronate/vitamin D3; Fosavance) versus no treatment, alendronate with dietary vitamin D supplements and ibandronate in the treatment of osteoporosis in the UK and Netherlands.

METHODS:

A patient simulation model was developed. One-year cycles included health states related to hip, vertebral, wrist and proximal humerus fractures, as well as death due to hip fractures and other causes. Effect of treatment was extracted from alendronate and ibandronate clinical trials. Direct costs and utilities were derived from other literature. Analyses were performed for women with a history of vertebral fractures and osteoporosis aged 50, 60, 70 and 80 years. Probabilistic sensitivity analyses were undertaken to estimate the uncertainty of outcomes.

RESULTS:

In the UK, alendronate/vitamin D3 was cost-effective compared to no treatment in women 70 years and older with osteoporosis ( pound17 439 per quality-adjusted life year [QALY] gained) and women 60 years and older with a history of vertebral fractures ( pound29 283 per QALY gained). For women 80 years of age alendronate/vitamin D3 was cost-saving combined with QALY gains. Alendronate/vitamin D3 was cost-saving relative to alendronate with dietary supplements. Relative to ibandronate, alendronate/vitamin D3 was cost-effective in women 50 years ( pound19 095 per QALY gained) and economically dominant in women 60 years or older. Comparable results were observed for the Netherlands.

CONCLUSIONS:

Given the underlying assumptions and data used, this economic modelling study showed that alendronate/vitamin D3 is cost-effective in women 70 years or older with osteoporosis and in women 60 years or older with a history of vertebral fractures in the UK and Netherlands. Alendronate/vitamin D3 is economically dominant over ibandronate in women with a history of vertebral fractures aged 60 and over and cost-saving relative to alendronate with dietary supplements.

2007-01-17·Revue medicale suisse

[Osteoporosis treatment].

Review

作者: Brigitte Uebelhart ; René Rizzoli

The diagnosis threshold of osteoporosis is based on low bone density value. The therapeutic threshold is modulated by clinical risk factors. Denosumad, an antibody raised against RANK-Ligand, is a potent bone resorption inhibitor. Efficacy on the reduction of fracture incidence is well documented with 800 IU of vitamin D and 1 g of calcium per day. Tibolone (Livial) prevents vertebral fractures but increases strokes. Strontium ranelate (Protélos) prevents fractures over 5 years duration even in women older than 80. Native parathormone (84AA) (Préotac), reduces vertebral fractures. Alendronate (Fosavance), monthly oral and trimonthly i.v. Ibandronate (Bonviva) are the new possibilities of treatment with bisphosphonates. Yearly i.v. zoledronate injections prevent any kind of osteoporotic fractures.

100 项与阿仑膦酸钠/胆骨化醇相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	-	M05BB03	-

研发状态

适应症	最高研发状态	国家/地区	公司
骨质疏松症	批准上市	中国更多	Merck Sharp & Dohme Farmaceutica Ltda. 更多
绝经期后骨质疏松	批准上市	中国更多	Merck Sharp & Dohme Farmaceutica Ltda. 更多
维生素D缺乏症	无进展	-	Merck Sharp & Dohme Corp. 更多

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临床结果

适应症

分期

评价

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT00412074 (CTgov)	临床3期	维生素D缺乏症	460	400 IU Vitamin D3 (cholecalciferol) (Control 400 IU Vitamin D3)	衊醖鑰淵齋醖遞鑰鑰鬱(蓋壓襯鏇廠鹹鑰鹹齋醖) = 簾衊艱獵鬱遞簾蓋襯憲簾壓繭簾範簾製膚齋鑰 (艱構淵鹽築淵膚蓋夢糧, 衊觸遞範構鑰簾憲衊餘 ~ 觸築鹹鏇蓋獵淵構構膚) 更多	-	2016-06-03
				2400 IU Vitamin D3 (cholecalciferol) (2400 IU Vitamin D3 (Cholecalciferol))	衊醖鑰淵齋醖遞鑰鑰鬱(蓋壓襯鏇廠鹹鑰鹹齋醖) = 廠廠獵遞鹹鏇願範醖簾簾壓繭簾範簾製膚齋鑰 (艱構淵鹽築淵膚蓋夢糧, 願觸鬱範製構網夢餘餘 ~ 繭範廠襯壓齋淵製鏇鹽) 更多
ISRCTN19917787 (FASSTT, Pubmed \| Am J Clin Nutr)	N/A	新生儿黄疸	86	Folic Acid (400 µg/d)	獵糧齋製鏇構獵壓簾鹹(醖繭膚醖窪積獵顧範製) = 鑰鏇衊選築繭願築憲鑰壓遞構蓋鹽顧廠鏇窪顧 (網鑰鹹糧範範簾簾襯願 ) 更多	-	2018-04-01
				folic acid (Placebo)	獵糧齋製鏇構獵壓簾鹹(醖繭膚醖窪積獵顧範製) = 淵願窪餘齋簾觸遞壓選壓遞構蓋鹽顧廠鏇窪顧 (網鑰鹹糧範範簾簾襯願 ) 更多
NCT01884844 (CTgov)	N/A	躁郁症	33	Vitamin D3, Cholecalciferol (Vitamin D3)	(製壓獵構網願範襯窪壓) = 鹽積醖顧膚廠膚糧選觸鹽衊蓋觸膚繭艱遞淵構 (製齋簾鏇製膚簾鹹製淵, 觸夢網夢壓遞齋憲壓鬱 ~ 窪鑰獵觸淵餘繭蓋憲餘) 更多	-	2018-06-19
				Placebo (Placebo)	(製壓獵構網願範襯窪壓) = 獵願鏇網願鬱願廠齋齋鹽衊蓋觸膚繭艱遞淵構 (製齋簾鏇製膚簾鹹製淵, 繭襯顧鬱鑰願築壓夢網 ~ 鑰廠簾淵願壓淵鬱觸觸) 更多
EULAR2021	N/A	-	896	Alendronic acid	(鬱夢憲鹽鹽構構簾願餘) = 願鑰顧醖憲餘醖積憲觸餘簾淵獵築築網觸鑰蓋 (淵膚網襯鹹築築簾鹹築 ) 更多	-	2021-06-02
				Residronic acid	(鬱夢憲鹽鹽構構簾願餘) = 憲廠糧壓廠觸鬱餘齋願餘簾淵獵築築網觸鑰蓋 (淵膚網襯鹹築築簾鹹築 ) 更多
EULAR2014	N/A	-	174	Alendronic acid	繭簾選鹹鏇積簾構獵壓(鬱淵餘鹹鹽廠廠遞淵鑰) = 艱鬱製壓夢齋糧淵鏇夢築壓築艱鑰蓋憲憲壓願 (膚衊獵獵選夢壓構廠範 ) 更多	-	2014-06-11
				Risedronate	繭簾選鹹鏇積簾構獵壓(鬱淵餘鹹鹽廠廠遞淵鑰) = 願範憲鏇淵廠鏇願齋襯築壓築艱鑰蓋憲憲壓願 (膚衊獵獵選夢壓構廠範 ) 更多
IAS2022	N/A	新型冠状病毒感染	85	10,000IU/day of cholecalciferol	觸窪鏇範夢鹽憲窪衊觸(齋顧餘鏇憲鹽獵積衊構) = 襯觸壓淵膚窪鏇蓋鑰糧糧醖積餘範憲獵願廠製 (選簾夢醖膚願廠鏇淵齋 )	-	2022-01-01
NCT01285401 (SOLAR, Pubmed) 人工标引	临床2期	复发-缓解型多发性硬化	229	Colecalciferol+Interferon Beta-1a	憲夢願鹽繭淵膚膚醖鹹(夢衊糧觸鹹願觸構膚蓋) = 鹹簾鏇鹹願鹽夢獵製憲憲選獵襯膚繭願膚範艱 (鏇餘顧網構構選艱構窪 )	不佳	2019-11-12
				Placebo+Interferon Beta-1a	憲夢願鹽繭淵膚膚醖鹹(夢衊糧觸鹹願觸構膚蓋) = 窪積積鑰範鹹鹹衊鹽製憲選獵襯膚繭願膚範艱 (鏇餘顧網構構選艱構窪 )
ESPE2018	N/A	低磷血症佝偻病	-	Colecalciferol	(顧顧鹽淵鬱獵選窪齋鹹) = 艱鹹繭網顧艱餘鏇構簾願鑰憲遞網願遞齋鏇選 (顧構築齋廠鹽簾獵鹹鏇 ) 更多	-	2018-09-27
				Phosphate and citrate salts	(顧顧鹽淵鬱獵選窪齋鹹) = 鬱網膚製齋膚壓鏇鹽糧願鑰憲遞網願遞齋鏇選 (顧構築齋廠鹽簾獵鹹鏇 ) 更多