Alendronic acid

Template:Short description Template:Use dmy dates Template:Cs1 config Template:Main other {{#invoke:Infobox|infobox}}Template:Template other{{#invoke:TemplatePar |check |template=Template:Infobox_drug |all= |opt= pronounce= pronounce_ref= pronounce_comment= ATC_prefix= ATC_suffix= ATC_supplemental= ATCvet= biosimilars= CAS_number_Ref= CAS_number= CAS_supplemental= ChEBI= ChEBI_Ref= ChEMBL_Ref= ChEMBL= ChemSpiderID= ChemSpiderID_Ref= chirality= class= container_only= DailyMedID= data_page= DrugBank_Ref= DrugBank= Drugs.com= duration_of_action= INN= INN_EMA= IUPAC_name= IUPHAR_ligand= KEGG_Ref= KEGG= MedlinePlus= NIAID_ChemDB= PDB_ligand= PubChemSubstance= PubChem= StdInChIKey_Ref= StdInChIKey= StdInChI_Ref= StdInChI_comment= StdInChI= UNII_Ref= UNII= DTXSID= Verifiedfields= Watchedfields= addiction_liability= alt2= altL= altR= alt= bioavailability= boiling_high= boiling_notes= boiling_point= captionLR= caption= caption2= charge= chemical_formula= chemical_formula_ref= chemical_formula_comment= class1= class2= class3= class4= class5= class6= component1= component2= component3= component4= component5= component6= density= density_notes= dependency_liability= drug_name= elimination_half-life= engvar= excretion= image2= imageL= imageR= image= image_class= image_class2= image_classL= image_classR= Jmol= legal_AU= legal_BR= legal_CA= legal_DE= legal_EU= legal_NZ= legal_UK= legal_UN= legal_US= legal_AU_comment= legal_BR_comment= legal_CA_comment= legal_DE_comment= legal_UK_comment= legal_NZ_comment= legal_US_comment= legal_UN_comment= legal_EU_comment= legal_status= licence_CA= licence_EU= licence_US= license_CA= license_EU= license_US= mab_type= melting_high= melting_notes= melting_point= metabolism= metabolites= molecular_weight= molecular_weight_round= molecular_weight_unit= molecular_weight_ref= molecular_weight_comment= onset= pregnancy_AU= pregnancy_AU_comment= pregnancy_category= protein_bound= routes_of_administration= SMILES= smiles= solubility= sol_units= source= specific_rotation= synonyms= target= tradename= type= vaccine_type= verifiedrevid= width2= widthL= widthR= width= AAN= BAN= JAN= USAN= source_tissues= target_tissues= receptors= agonists= antagonists= precursor= biosynthesis= gt_target_gene= gt_vector= gt_nucleic_acid_type= gt_editing_method= gt_delivery_method= sec_combustion= Ac=Ag=Al=Am=Ar=As=At=Au=B=Ba=Be=Bh=Bi=Bk=Br=C=Ca=Cd=Ce=Cf=Cl=Cm=Cn=Co=Cr=Cs=Cu= D=Db=Ds=Dy=Er=Es=Eu=F=Fe=Fl=Fm=Fr=Ga=Gd=Ge=H=He=Hf=Hg=Ho=Hs=I=In=Ir=K=Kr=La=Li=Lr=Lu=Lv= Mc=Md=Mg=Mn=Mo=Mt=N=Na=Nb=Nd=Ne=Nh=Ni=No=Np=O=Og=Os=P=Pa=Pb=Pd=Pm=Po=Pr=Pt=Pu=Ra=Rb=Re=Rf=Rg=Rh=Rn=Ru=S=Sb=Sc=Se=Sg=Si=Sm=Sn=Sr=Ta=Tb=Tc=Te=Th=Ti=Tl=Tm=Ts=U=V=W=Xe=Y=Yb=Zn=Zr= index_label= index2_label= index_comment= index2_comment= CAS_number2= CAS_supplemental2= ATC_prefix2= ATC_suffix2= ATC_supplemental2= PubChem2= PubChemSubstance2= IUPHAR_ligand2= DrugBank2= ChemSpiderID2= UNII2= KEGG2= ChEBI2= ChEMBL2= PDB_ligand2= NIAID_ChemDB2= SMILES2= smiles2= StdInChI2= StdInChIKey2= CAS_number2_Ref= ChEBI2_Ref= ChEMBL2_Ref= ChemSpiderID2_Ref= DrugBank2_Ref= KEGG2_Ref= StdInChI2_Ref= StdInChIKey2_Ref= UNII2_Ref= DTXSID2= QID= QID2=PLLR= pregnancy_US= pregnancy_US_comment= |cat=Pages using infobox drug with unknown parameters |format=0|errNS=0

|preview=

}}{{Infobox drug/maintenance categoriesTemplate:Yesno | drug_name = | INN = | _drugtype =

| _has_physiological_data= | _has_gene_therapy=

| vaccine_type= | mab_type= | _number_of_combo_chemicals={{#invoke:ParameterCount |main |component1 |component2 |component3 |component4|component5|component6 }} | _vaccine_data= | _mab_data= | _mab_vaccine_data= | _mab_other_data=41317O=P(O)(O)C(O)(CCCN)P(=O)(O)O1S/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)OGSPWJRAVKPPFI-UHFFFAOYSA-NTemplate:StdinchiciteTemplate:Stdinchicite | _combo_data= | _physiological_data= | _clinical_data=Template:Drugs.coma601011Alendronate sodium <ref name="Drugs.com pregnancy">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>B3By mouthFosamax, Binosto, othersM05 | _legal_data=<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>Rx-onlyPOM<ref name="Fosamax FDA label">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>Rx-only

| _other_data=sodium [4-amino-1-hydroxy-1-(hydroxy-oxido-phosphoryl)- butyl]phosphonic acid trihydrate

| _image_0_or_2 = Alendronic acid.svgAlendronate-3D-balls.png | _image_LR =

| _datapage = Alendronic acid (data page) | _vaccine_target={{#ifeq: | vaccine | | _type_not_vaccine }} | _legal_all=Rx-onlyPOMRx-only | _ATC_prefix_supplemental=M05 | _has_EMA_link = | CAS_number=66376-36-1 | PubChem=2088 | ChemSpiderID=2004 | ChEBI=2567 | ChEMBL=870 | DrugBank=DB00630 | KEGG=D07119 | _hasInChI_or_Key={{#if: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)OGSPWJRAVKPPFI-UHFFFAOYSA-N |yes}} | UNII=X1J18R4W8P | _hasJmol02 = |_hasMultipleCASnumbers = 121268-17-5 |_hasMultiplePubChemCIDs = |_hasMultipleChEBIs =

| _countSecondIDs={{#invoke:ParameterCount |main |CAS_number2 |ATC_prefix2 |PubChem2 |PubChemStructure2 |IUPHAR_ligand2 |DrugBank2 |ChemSpiderID2 |UNII2 |KEGG2 |ChEBI2 |ChEMBL2 |PDB_ligand2 |NIAID_ChemDB2 |SMILES2 |smiles2 |StdInChI2 |StdInChIKey2 |DTXCID2}} | _countIndexlabels={{#invoke:ParameterCount |main |index_label |index2_label}} | _trackListSortletter= |QID = |QID2 = |Verifiedfields=changed |Watchedfields=changed |verifiedrevid=477314835}}

Alendronic acid, sold under the brand name Fosamax among others, is a bisphosphonate medication used to treat osteoporosis and Paget's disease of bone.<ref name=AHFS2019/> It is taken by mouth.<ref name=AHFS2019/> Use is often recommended together with vitamin D, calcium supplementation, and lifestyle changes.<ref name=AHFS2019>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

Common side effects (1 to 10% of patients) include constipation, abdominal pain, nausea, and acid reflux.<ref name=AHFS2019/> Use is not recommended during pregnancy or in those with poor kidney function.<ref name=BNF76>Template:Cite book</ref> Alendronic acid works by decreasing the activity of cells that break down bone.<ref name=AHFS2019/>

Alendronic acid was first described in 1978 and approved for medical use in the United States in 1995.<ref name=AHFS2019/><ref name=Fis2006>Template:Cite book</ref> It is available as a generic medication. In 2022, it was the 103rd most commonly prescribed medication in the United States, with more than 6Template:Nbspmillion prescriptions.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

Medical uses

Alendronic acid is indicated for the treatment and prevention of osteoporosis in postmenopausal women;<ref name="Fosamax FDA label" /> the treatment to increase bone mass in men with osteoporosis;<ref name="Fosamax FDA label" /> the treatment of glucocorticoid-induced osteoporosis;<ref name="Fosamax FDA label" /> and the treatment of Paget's disease of bone.<ref name="Fosamax FDA label" /><ref name=AHFS2019 />

Side effects

• Gastrointestinal tract:
  • Ulceration and possible rupture of the esophagus; this may require hospitalization and intensive treatment. Gastric and duodenal ulceration may also occur.
  • Esophageal cancer, a meta-analysis concluded that bisphosphonate treatment is NOT associated with excess risk of esophageal cancer.<ref name="pmid23052941">Template:Cite journal</ref><ref name="pmid22333262">Template:Cite journal</ref>
• General: infrequent cases of skin rash, rarely manifesting as Stevens–Johnson syndrome and toxic epidermal necrolysis, eye problems (uveitis, scleritis) and generalized muscle, joint, and bone pain<ref>{{#invoke:citation/CS1|citation

|CitationClass=web }}</ref> (rarely severe) have been reported.

• Osteonecrosis of the jaw may occur while on this drug, if dental work of any kind is carried out. The risk is considerably higher for extractions in the mandible (lower jaw) than other areas of the mouth, and the risk increases if you have been taking it for four or more years <ref>{{#invoke:citation/CS1|citation

|CitationClass=web }}</ref> Although this side effect is uncommon (0.4-1.6% for oral alendronic acid), it occurs primarily in patients being administered intravenous bisphosphonates, with most cases being reported in cancer patients.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref>

• Bone: alendronate has been linked in long-term users to the development of low-impact femoral fractures.<ref name="pmid18354114">Template:Cite journal
• Template:Lay source</ref> Further, studies suggest that users of alendronate have an increase in the numbers of osteoclasts and develop giant, more multinucleated osteoclasts; the significance of this development is unclear.<ref name="pmid19118304">Template:Cite journal
• Template:Lay source</ref> Fosamax has been linked to a rare type of leg fracture that cuts straight across the upper thigh bone after little or no trauma (subtrochanteric fractures).<ref name="pmid18222447">Template:Cite journal</ref>

Pharmacology

Mechanism of action

Nitrogen containing bisphosphonates, which include ibandronate, pamidronate and alendronate exert their effects on osteoclasts mainly by inhibiting the synthesis of isoprenoid lipids such as isopentenyl diphosphate (IPP), farnesyl diphosphate (FPP), and geranylgeranyl diphosphate (GGPP) via the mevalonate pathway. These isoprenoids are used in posttranslational modification(prenylation) of small GTPases such as Ras, Rho, and Rac. These prenylated GTPases are necessary for various cellular processes including osteoclast morphology, endosome trafficking, and apoptosis. Alendronate has also been shown to impair the function of osteclast lysosomes.<ref>Template:Cite journal</ref>

Relative potency<ref>Template:Cite book</ref>

Bisphosphonate	Relative potency
Etidronate	1
Tiludronate	10
Pamidronate	100
Alendronate	100-500
Ibandronate	500-1000
Risedronate	1000
Zoledronate	5000

Pharmacokinetics

The fraction of the drug that reaches the circulatory system intact (systemic bioavailability) after oral dosing is low, averaging only 0.6–0.7% in women and in men under fasting conditions. Intake together with meals and beverages other than water further reduces the bioavailability. The absorbed drug rapidly partitions, with approximately 50% binding to the exposed bone surface; the remainder is excreted unchanged by the kidneys. Unlike with most drugs, the strong negative charge on the two phosphonate moieties limits oral bioavailability, and, in turn, the exposure to tissues other than bone is very low. After absorption in the bone, alendronate has an estimated terminal elimination half-life of 10 years.<ref name="pmid8689235">Template:Cite journal</ref>