ALENDRONIC ACID

Details

Stereochemistry	ACHIRAL
Molecular Formula	C4H13NO7P2
Molecular Weight	249.096
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

NCCCC(O)(P(O)(O)=O)P(O)(O)=O

InChI

InChIKey=OGSPWJRAVKPPFI-UHFFFAOYSA-N

InChI=1S/C4H13NO7P2/c5-3-1-2-4(6,13(7,8)9)14(10,11)12/h6H,1-3,5H2,(H2,7,8,9)(H2,10,11,12)

HIDE SMILES / InChI

Description
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/020560s069,021575s025lbl.pdf

Alendronic acid is a bisphosphonate drug used for osteoporosis, osteogenesis imperfecta, and several other bone diseases. It is marketed alone as well as in combination with vitamin D. Alendronate inhibits osteoclast-mediated bone-resorption. Like all bisphosphonates, it is chemically related to inorganic pyrophosphate, the endogenous regulator of bone turnover. But while pyrophosphate inhibits both osteoclastic bone resorption and the mineralization of the bone newly formed by osteoblasts, alendronate specifically inhibits bone resorption without any effect on mineralization at pharmacologically achievable doses. Its inhibition of bone-resorption is dose-dependent and approximately 1,000 times stronger than the equimolar effect of the first bisphosphonate drug, etidronate. Under therapy, normal bone tissue develops, and alendronate is deposited in the bone-matrix in a pharmacologically inactive form. For optimal action, enough calcium and vitamin D are needed in the body in order to promote normal bone development. Hypocalcemia should, therefore, be corrected before starting therapy. Treatment of post-menopausal women and people with osteogenesis imperfecta over the age of 22 with alendronic acid has demonstrated normalization of the rate of bone turnover, significant increase in BMD (bone mineral density) of the spine, hip, wrist and total body, and significant reductions in the risk of vertebral (spine) fractures, wrist fractures, hip fractures, and all non-vertebral fractures. In the Fracture Intervention Trial, the women with the highest risk of fracture (by virtue of pre-existing vertebral fractures) were treated with Fosamax 5 mg/day for two years followed by 10 mg/day for the third year. This resulted in approximately 50% reductions in fractures of the spine, hip, and wrist compared with the control group taking placebos. Both groups also took calcium and vitamin D.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Farnesyl diphosphate synthase 28 Target ID: CHEMBL1782 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18327899	Inhibitor 8146		260.0 nM [IC50]
Geranylgeranyl pyrophosphate synthetase 18 Target ID: CHEMBL4769 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18800762	Inhibitor 8146		436.52 µM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Osteoporosis 97 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/020560s069,021575s025lbl.pdf	Primary	Approved 8307	FOSAMAX Approved Use INDICATIONS AND USAGE. FOSAMAX is a bisphosphonate indicated for: Treatment and prevention of osteoporosis in postmenopausal women (1.1, 1.2) Treatment to increase bone mass in men with osteoporosis (1.3) Treatment of glucocorticoid-induced osteoporosis (1.4) Treatment of Paget's disease of bone (1.5) Important limitations of use: The optimal duration of use has not been determined. The need for continued therapy should be re-evaluated on a periodic basis. (1.6) Launch Date 9.3381119E11
Glucocorticoid-induced osteoporosis 11 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/020560s069,021575s025lbl.pdf	Primary	Approved 8307	FOSAMAX Approved Use INDICATIONS AND USAGE. FOSAMAX is a bisphosphonate indicated for: Treatment and prevention of osteoporosis in postmenopausal women (1.1, 1.2) Treatment to increase bone mass in men with osteoporosis (1.3) Treatment of glucocorticoid-induced osteoporosis (1.4) Treatment of Paget's disease of bone (1.5) Important limitations of use: The optimal duration of use has not been determined. The need for continued therapy should be re-evaluated on a periodic basis. (1.6) Launch Date 9.3381119E11
Paget's disease 16 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/020560s069,021575s025lbl.pdf	Primary	Approved 8307	FOSAMAX Approved Use INDICATIONS AND USAGE. FOSAMAX is a bisphosphonate indicated for: Treatment and prevention of osteoporosis in postmenopausal women (1.1, 1.2) Treatment to increase bone mass in men with osteoporosis (1.3) Treatment of glucocorticoid-induced osteoporosis (1.4) Treatment of Paget's disease of bone (1.5) Important limitations of use: The optimal duration of use has not been determined. The need for continued therapy should be re-evaluated on a periodic basis. (1.6) Launch Date 9.3381119E11

C_max

Value	Dose	Co-administered	Analyte	Population
56.62 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/28744102	70 mg single, oral dose: 70 mg route of administration: Oral experiment type: SINGLE co-administered:		ALENDRONATE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
155.53 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/28744102	70 mg single, oral dose: 70 mg route of administration: Oral experiment type: SINGLE co-administered:		ALENDRONATE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
1.73 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/28744102	70 mg single, oral dose: 70 mg route of administration: Oral experiment type: SINGLE co-administered:		ALENDRONATE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:2567	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:2567
ChemicalBook	CB3380835	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB3380835
ZINC	ZINC000003801919	http://zinc15.docking.org/substances/ZINC000003801919
eMolecules	901346	https://www.emolecules.com/cgi-bin/more?vid=901346

PubMed

Title	Date	PubMed
The effect of alendronate on fracture-related healthcare utilization and costs: the fracture intervention trial.	2001	11580079
Cost effectiveness of nasal calcitonin in postmenopausal women: use of Cochrane Collaboration methods for meta-analysis within economic evaluation.	2001	11465301
Alendronate influences bending force of femoral diaphysis after orchidectomy in rats.	2001	11459259
Initiation of osteoporosis treatment after bone mineral density testing.	2001	11444079
Bone loss. Therapeutic approaches for preventing bone loss in inflammatory arthritis.	2001	11438040
Alendronate: an update of its use in osteoporosis.	2001	11434454
Comparison of bone and total alkaline phosphatase and bone mineral density in postmenopausal osteoporotic women treated with alendronate.	2001	11420777
Inhibition of leukotriene function can modulate particulate-induced changes in bone cell differentiation and activity.	2001	11410899
A controlled study of the effects of alendronate in a growing mouse model of osteogenesis imperfecta.	2001 Aug	11683430
Guidelines for treatment of osteoporosis in men.	2001 Aug	11681154
Alendronate increases degree and uniformity of mineralization in cancellous bone and decreases the porosity in cortical bone of osteoporotic women.	2001 Aug	11502482
Effect of alendronate on bone mineral density in male idiopathic osteoporosis.	2001 Aug	11474478
Effect of 17beta-estradiol or alendronate on the bone densitometry, bone histomorphometry and bone metabolism of ovariectomized rats.	2001 Aug	11471040
Alendronate treatment for osteoporosis in patients infected with human immunodeficiency virus.	2001 Aug 1	11438917
Fosamax for HIV-related bone problems?	2001 Jul	11569991
Emerging therapies in osteoporosis.	2001 Jul	11485342
Role of bisphosphonates and calcitonin in the prevention and treatment of osteoporosis.	2001 Jul	11485341
Male osteoporosis associated with longterm cyproterone treatment.	2001 Jul	11469484
Additional beneficial effects of alendronate in growth hormone (GH)-deficient adults with osteoporosis receiving long-term recombinant human GH replacement therapy: a randomized controlled trial.	2001 Jul	11443170
[Bisphosphonate treatment prevents hip fractures in 70-79 year old women with osteoporotic vertebral fractures].	2001 Jul 14	11484428
[Osteoporosis and multiple pregnancy--a case report with positive outcome].	2001 Jul 15	11494915
The use of scintigraphy to demonstrate the rapid esophageal transit of the oval film-coated placebo risedronate tablet compared to a round uncoated placebo tablet when administered with minimal volumes of water.	2001 Jul 17	11427359
[Modern osteoporosis therapy. Only once weekly against osteoporosis].	2001 Jul 19	11499150
[Bisphosphonates once weekly. Osteoporosis therapy becomes more effective].	2001 Jul 26	11524987
New possibilities for diagnosis and treatment of osteoporosis.	2001 Jul-Aug	11563832
American Association of Clinical Endocrinologists 2001 Medical Guidelines for Clinical Practice for the Prevention and Management of Postmenopausal Osteoporosis.	2001 Jul-Aug	11508261
Effect of topical alendronate on root resorption of dried replanted dog teeth.	2001 Jun	11499761
Medication update.	2001 Jun	11440325
Prevalence and determinants of osteoporosis drug prescription among patients with high exposure to glucocorticoid drugs.	2001 Jun	11439733
Re: Lanza et al.--Endoscopic comparison of alendronate and risedronate.	2001 Jun	11419858
Osteoporosis.	2001 Jun	11402788
Osteoporosis in men.	2001 Jun 15	11430449
[Esophagitis associated with use of alendronate in 5 postmenopausic patients].	2001 May	11471319
[Effects of aminobisphosphonates on the superior digestive tract mucosa].	2001 May	11471318
Why do older women discontinue hormone replacement therapy?	2001 May	11445025
Bones and Crohn's: should we treat Crohn's disease patients with alendronate?	2001 May	11383592
[Treatment of osteoporosis. Compliance is significantly enhanced].	2001 May 31	11460408
[Radiopharmacokinetic and gammagraphic studies for calculating personalized dosimetry].	2001 May-Jun	11496710
Nitrogen-containing bisphosphonates induce apoptosis of Caco-2 cells in vitro by inhibiting the mevalonate pathway: a model of bisphosphonate-induced gastrointestinal toxicity.	2001 Oct	11595616
Prevention of bone loss and fracture after lung transplantation: a pilot study.	2001 Oct 15	11602851
Comparison of calcitonin, alendronate and fluorophosphate effects on ovariectomized rat bone.	2001 Sep	11669503
The molecular mechanism of action of the antiresorptive and antiinflammatory drug clodronate: evidence for the formation in vivo of a metabolite that inhibits bone resorption and causes osteoclast and macrophage apoptosis.	2001 Sep	11592386
Risedronate: a new oral bisphosphonate.	2001 Sep	11589256
Bisphosphonates for osteoporosis.	2001 Sep	11586803
Update on alendronate for osteoporosis: once-weekly dosing.	2001 Sep	11585024
Isoprenoid biosynthesis. Metabolite profiling of peppermint oil gland secretory cells and application to herbicide target analysis.	2001 Sep	11553758
Bisphosphonate therapy for Paget's disease in a patient with hypoparathyroidism: profound hypocalcemia, rapid response, and prolonged remission.	2001 Sep	11547843
Alendronate does not interfere with 99mTc-methylene diphosphonate bone scanning.	2001 Sep	11535725
Pharmacologic therapy for the treatment and prevention of osteoporosis.	2001 Sep	11532658
Vgamma2Vdelta2 T-cell receptor-mediated recognition of aminobisphosphonates.	2001 Sep 1	11520816

Patents

Sample Use Guides

In Vivo Use Guide

Treatment of Osteoporosis in Postmenopausal Women: one 70 mg tablet once weekly Prevention of Osteoporosis in Postmenopausal Women: one 35 mg tablet once weekly Treatment to Increase Bone Mass in Men with Osteoporosis: one 70 mg tablet once weekly

Route of Administration: Oral

In Vitro Use Guide

IGROV-1 ovarian carcinoma cells were stained with PKH26 (Sigma-Aldrich) according to the manufacturer’s instructions and then incubated with the indicated AA (Alendronic acid ) for 24 h. After washing, 1 3 106 target cells and 1 3 106 ex vivo expanded gd T cells were cocultured at 37°C/5% CO2 for 4 h and then stained with Annexin VFITC (BD Pharmingen)

Name

Type

Language

ALENDRONIC ACID

Official Name

English

ALENDRONIC ACID [EMA EPAR]

Common Name

English

P,P'-(4-AMINO-1-HYDROXYBUTYLIDENE)BISPHOSPHONIC ACID

Systematic Name

English

.ALPHA.-HYDROXY-.DELTA.-AMINOBUTYLIDENEDIPHOSPHONIC ACID

Systematic Name

English

ABDP

Common Name

English

ALENDRONATE [VANDF]

Common Name

English

(4-AMINO-1-HYDROXYBUTYLIDENE)DIPHOSPHONIC ACID

Systematic Name

English

PHOSPHONIC ACID, (4-AMINO-1-HYDROXYBUTYLIDENE)BIS-

Common Name

English

alendronic acid [INN]

Common Name

English

PHOSPHONIC ACID, P,P'-(4-AMINO-1-HYDROXYBUTYLIDENE)BIS-

Common Name

English

4-AMINO-1-HYDROXYBUTANE-1,1-DIPHOSPHONIC ACID

Systematic Name

English

ALENDRONATE [MART.]

Common Name

English

(4-AMINO-1-HYDROXYBUTANE-1,1-DIYL)BIS(PHOSPHONIC ACID)

Systematic Name

English

ALENDRONIC ACID [MI]

Common Name

English

ALENDRONATE

Common Name

English

Alendronic acid [WHO-DD]

Common Name

English

Classification Tree Code System Code

FDA ORPHAN DRUG

166603