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{{Short description|Chemical compound}}
{{drugbox
{{cs1 config|name-list-style=vanc}}
| verifiedrevid = 389389694
{{Drugbox
| IUPAC_name = (1-hydroxy-2-imidazol-1-yl-1-phosphono-ethyl)phosphonic acid
| Verifiedfields = changed
| verifiedrevid = 396274597
| image = Zoledronic acid.svg
| image = Zoledronic acid.svg
| image2 = Zoledronate-3D-balls.png
| width = 180px
| width = 180px
| image2 = Zoledronic-acid-from-xtal-2003-3D-balls.png
| CASNo_Ref = {{cascite}}

| CAS_number = 118072-93-8
<!--Clinical data-->
| tradename = Reclast, Zometa, others<ref name=drugs.comINT>{{cite web | work = Drugs.com | url = https://www.drugs.com/international/zoledronic-acid.html | title = International trade names for zoledronic acid | access-date = 14 January 2015 }}</ref>
| Drugs.com = {{drugs.com|monograph|zoledronic_acid}}
| MedlinePlus = a605023
| licence_EU = yes
| DailyMedID = Zoledronic_acid
| licence_US = Zoledronic_acid
| pregnancy_AU = B3
| pregnancy_AU_comment = <ref name="Drugs.com pregnancy">{{cite web | title=Zoledronic acid Use During Pregnancy | website=Drugs.com | date=1 June 2020 | url=https://www.drugs.com/pregnancy/zoledronic-acid.html | access-date=19 October 2020}}</ref>
| pregnancy_US = D
| pregnancy_US_comment = <ref name="Drugs.com pregnancy" />
| pregnancy_category=
| dependency_liability =
| addiction_liability =
| routes_of_administration = [[Intravenous therapy|Intravenous]]
| class = [[Bisphosphonate]]<ref name=AHFS2017/>
| ATC_prefix = M05
| ATC_prefix = M05
| ATC_suffix = BA08
| ATC_suffix = BA08

| PubChem = 68740
| DrugBank = APRD01294
| legal_US = Rx-only
| legal_EU = Rx-only
| C = 5 |H = 10 |N = 2 |O = 7 |P = 2

| molecular_weight = 272.09 [[Gram|g]]/[[Mole (unit)|mol]]
<!--Pharmacokinetic data-->
| bioavailability =
| bioavailability =
| protein_bound = 22%
| protein_bound = 22%
| metabolism = Nil
| metabolism = Nil
| elimination_half-life = 146 hours
| elimination_half-life = 146 hours
| excretion = [[Kidney|Renal]] (partial)
| excretion = [[Kidney]] (partial)

| licence_EU = Reclast
<!--Identifiers-->
| licence_US = Zoledronic_acid
| CAS_number = 118072-93-8
| pregnancy_category = D <small>([[United States|U.S.]])</small>
| PubChem = 68740
| legal_status = ℞-only <small>(U.S.)</small>
| IUPHAR_ligand = 3177
| routes_of_administration = [[Intravenous therapy|Intravenous]]
| DrugBank = DB00399
| ChemSpiderID = 61986
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 70HZ18PH24
| KEGG_Ref = {{keggcite|changed|kegg}}
| KEGG = D08689
| KEGG2_Ref = {{keggcite|changed|kegg}}
| KEGG2 = D01968
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 924
| PDB_ligand = ZOL
| ChEBI = 46557
| synonyms = zoledronate

<!--Chemical data-->
| IUPAC_name = [1-hydroxy-2-(1''H''-imidazol-1-yl)ethane-1,1-diyl]bis(phosphonic acid)
| C=5 | H=10 | N=2 | O=7 | P=2
| SMILES = O=P(O)(O)C(O)(Cn1ccnc1)P(=O)(O)O
| StdInChI = 1S/C5H10N2O7P2/c8-5(15(9,10)11,16(12,13)14)3-7-2-1-6-4-7/h1-2,4,8H,3H2,(H2,9,10,11)(H2,12,13,14)
| StdInChIKey = XRASPMIURGNCCH-UHFFFAOYSA-N
}}
}}
'''Zoledronic acid''' ([[International Nonproprietary Name|INN]]) or '''zoledronate''' (marketed by [[Novartis]] under the trade names '''Zometa''', '''Zomera''', '''Aclasta''' and '''Reclast''') is a [[bisphosphonate]]. Zometa is used to prevent [[skeletal]] [[fracture]]s in patients with [[cancer]]s such as [[multiple myeloma]] and [[prostate cancer]], as well as for treating [[osteoporosis]].<ref>National Prescribing Service (2009). "Zoledronic Acid for Osteoporosis". ''Medicines Update'', Available at http://www.nps.org.au/consumers/publications/medicine_update/issues/Zoledronic_acid</ref> It can also be used to treat [[hypercalcemia]] of malignancy and can be helpful for treating pain from bone metastases.


<!-- Definition and medical uses -->
An annual dose of zoledronic acid may also prevent recurring fractures in patients with a previous hip fracture.<ref>{{cite journal |author= Lyles K, et al.|title=Zoledronic Acid and Clinical Fractures and Mortality after Hip Fracture |journal=N. Engl. J. Med. |volume= 357|issue= 18|pages= 1799|year=2007 |pmid=17878149|doi=10.1056/NEJMoa074941}}</ref>
'''Zoledronic acid''', also known as '''zoledronate''' and sold under the brand name '''Zometa'''<ref>{{Cite web|title=PRESS RELEASE: Novartis's Reclast Receives FDA Approval FOR Women With Postmenopausal Osteoporosis|url=https://www.fiercebiotech.com/biotech/press-release-novartis-s-reclast-receives-fda-approval-for-women-postmenopausal|access-date=2021-09-02|website=FierceBiotech|date=20 August 2007 |language=en}}</ref> by [[Novartis]] among others, is a medication used to treat a number of [[bone disease]]s.<ref name=AHFS2017>{{cite web|title=Zoledronic Acid|url=https://www.drugs.com/monograph/zoledronic-acid.html|publisher=The American Society of Health-System Pharmacists|access-date= 8 December 2017}}</ref> These include [[osteoporosis]], [[hypercalcemia|high blood calcium]] due to [[cancer]], [[osteolytic lesion|bone breakdown]] due to cancer, [[Paget's disease of bone]]<ref name="AHFS2017" /> and [[Duchenne muscular dystrophy]] (DMD). It is given by [[intravenous|injection into a vein]].<ref name=AHFS2017/>


<!-- Side effects and mechanisms -->
Reclast is a single 5&nbsp;mg infusion for the treatment of [[Paget's disease of bone]]. In 2007, the [[Food and Drug Administration (United States)|U.S. Food and Drug Administration]] (FDA) also approved Reclast for the treatment of postmenopausal [[osteoporosis]].
Common side effects include [[fever]], [[joint pain]], [[high blood pressure]], diarrhea, and feeling tired.<ref name=AHFS2017/> Serious side effects may include [[kidney problems]], [[low blood calcium]], and [[osteonecrosis of the jaw]].<ref name=AHFS2017/> Use during [[pregnancy]] may result in harm to the baby.<ref name=AHFS2017/> It is in the [[bisphosphonate]] family of medications.<ref name=AHFS2017/> It works by blocking the activity of [[osteoclast cell]]s and thus decreases the breakdown of bone.<ref name=AHFS2017/>


<!-- History and culture -->
==Administration==
Zoledronic acid was patented in 1986 and approved for medical use in the United States in 2001.<ref name=AHFS2017/><ref name=Fis2006>{{cite book | vauthors = Fischer J, Ganellin CR |title=Analogue-based Drug Discovery |date=2006 |publisher=John Wiley & Sons |isbn=9783527607495 |page=524 |url=https://books.google.com/books?id=FjKfqkaKkAAC&pg=PA524 |language=en}}</ref> It is on the [[WHO Model List of Essential Medicines|World Health Organization's List of Essential Medicines]].<ref name="WHO21st">{{cite book | vauthors = ((World Health Organization)) | title = World Health Organization model list of essential medicines: 21st list 2019 | year = 2019 | hdl = 10665/325771 | author-link = World Health Organization | publisher = World Health Organization | location = Geneva | id = WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO | hdl-access=free }}</ref><ref name="WHO22nd">{{cite book | vauthors = ((World Health Organization)) | title = World Health Organization model list of essential medicines: 22nd list (2021) | year = 2021 | hdl = 10665/345533 | author-link = World Health Organization | publisher = World Health Organization | location = Geneva | id = WHO/MHP/HPS/EML/2021.02 | hdl-access=free }}</ref>
The standard dose for zoledronate is 4&nbsp;mg to be infused [[intravenous]]ly over 15 min every 3–4 weeks in cancer patients. For Reclast a single dose of 5&nbsp;mg is used for the treatment of Paget's disease.


==Medical uses==
Zoledronate has been approved as a once-yearly 5&nbsp;mg infusion for treatment of osteoporosis and shown significant benefits versus placebo over three years, with a reduced number of [[vertebral fracture]]s and improved markers of bone density.<ref>{{cite journal |author=Reid IR, Brown JP, Burckhardt P, Horowitz Z, Richardson P, Trechsel U, Widmer A, Devogelaer JP, Kaufman JM, Jaeger P, Body JJ, Brandi ML, Broell J, Di Micco R, Genazzani AR, Felsenberg D, Happ J, Hooper MJ, Ittner J, Leb G, Mallmin H, Murray T, Ortolani S, Rubinacci A, Saaf M, Samsioe G, Verbruggen L, Meunier PJ |title=Intravenous zoledronic acid in postmenopausal women with low bone mineral density |journal=N. Engl. J. Med. |volume=346 |issue=9 |pages=653–61 |year=2002 |pmid=11870242 |doi=10.1056/NEJMoa011807}}</ref><ref>Black et al.. Once-Yearly Zoledronic Acid for Treatment of Postmenopausal Osteoporosis. NEJM 2007;356;18;1809-1822. [http://content.nejm.org/cgi/content/short/356/18/1809 Abstract]</ref>


===Bone complications of cancer===
==Side effects==
Side effects can include [[fatigue (physical)|fatigue]], [[anemia]], [[muscle pain|muscle aches]], [[fever]], and/or [[Edema|swelling]] in the feet or legs. [[Flu-like symptoms]] are commonly experienced after the first zoledronate infusion, although not subsequent infusions, and are thought to occur because of its potential to activate human [[γδ T cells]] (gamma/delta T cells).


Zoledronic acid is used to prevent [[Bone fracture|bone fractures]] in patients with [[cancer]]s such as [[multiple myeloma]] and [[prostate cancer]], as well as for treating [[osteoporosis]].<ref>National Prescribing Service (2009). "Zoledronic Acid for Osteoporosis". ''Medicines Update'', Available at {{cite web|url=http://www.nps.org.au/consumers/publications/medicine_update/issues/Zoledronic_acid |title=Zoledronic acid (Aclasta) for osteoporosis: National Prescribing Service Ltd NPS |access-date=January 20, 2010 |url-status=dead |archive-url=https://web.archive.org/web/20100423105839/http://www.nps.org.au/consumers/publications/medicine_update/issues/zoledronic_acid |archive-date=April 23, 2010 }}</ref> It can also be used to treat [[hypercalcemia|hypercalcaemia]] of malignancy and can be helpful for treating pain from [[Bone metastasis|bone metastases]].<ref name=zomera>{{cite web | title = Zomera prescribing information | url = https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/021223s028lbl.pdf | work = Novartis Pharmaceuticals Corporation | publisher = U.S. Food and Drug Administration | date = April 2014 }}</ref>
Zoledronate is rapidly processed via the [[kidney]]s; consequently its administration is not recommended for patients with reduced [[renal function]] or kidney disease.<ref>http://emc.medicines.org.uk/medicine/14062/SPC/Zometa+4mg+5ml+Concentrate+for+Solution+for+Infusion/</ref>


It can be given at home rather than in hospital. Such use has shown safety and quality-of-life benefits in people with [[breast cancer]] and bone metastases.<ref>{{cite journal | vauthors = Wardley A, Davidson N, Barrett-Lee P, Hong A, Mansi J, Dodwell D, Murphy R, Mason T, Cameron D | display-authors = 6 | title = Zoledronic acid significantly improves pain scores and quality of life in breast cancer patients with bone metastases: a randomised, crossover study of community vs hospital bisphosphonate administration | journal = British Journal of Cancer | volume = 92 | issue = 10 | pages = 1869–1876 | date = May 2005 | pmid = 15870721 | pmc = 2361764 | doi = 10.1038/sj.bjc.6602551 }}</ref>
A rare complication that has been recently observed in cancer patients being treated with bisphosphonates is [[osteonecrosis of the jaw]]. This has mainly been seen in patients with multiple myeloma treated with zoledronate who have had [[dental extraction]]s.<ref>{{cite journal |author=Durie BG, Katz M, Crowley J |title=Osteonecrosis of the jaw and bisphosphonates |journal=N. Engl. J. Med. |volume=353 |issue=1 |pages=99–102; discussion 99–102 |year=2005 |pmid=16000365 |doi=10.1056/NEJM200507073530120}}</ref>

===Osteoporosis===
Zoledronic acid, in brand name products '''Aclasta''' and '''Reclast''' among others,<ref>{{cite journal | vauthors = Dhillon S | title = Zoledronic Acid (Reclast<sup>®</sup>, Aclasta<sup>®</sup>): A Review in Osteoporosis | journal = Drugs | volume = 76 | issue = 17 | pages = 1683–1697 | date = November 2016 | pmid = 27864686 | doi = 10.1007/s40265-016-0662-4 | s2cid = 22079489 }}</ref> may be given as a 5&nbsp;mg infusion once per year for treatment of [[osteoporosis]] in men and post-menopausal women at increased risk of fracture.<ref name="Lyles">{{cite journal | vauthors = Lyles KW, Colón-Emeric CS, Magaziner JS, Adachi JD, Pieper CF, Mautalen C, Hyldstrup L, Recknor C, Nordsletten L, Moore KA, Lavecchia C, Zhang J, Mesenbrink P, Hodgson PK, Abrams K, Orloff JJ, Horowitz Z, Eriksen EF, Boonen S | display-authors = 6 | title = Zoledronic acid and clinical fractures and mortality after hip fracture | journal = The New England Journal of Medicine | volume = 357 | issue = 18 | pages = 1799–1809 | date = November 2007 | pmid = 17878149 | pmc = 2324066 | doi = 10.1056/NEJMoa074941 }}</ref>

In 2007, the U.S. [[Food and Drug Administration]] (FDA) also approved it for the treatment of postmenopausal [[osteoporosis]].<ref>{{cite press release | url = https://www.fiercebiotech.com/biotech/press-release-novartis-s-reclast-receives-fda-approval-for-women-postmenopausal | title = Biotech PRESS RELEASE: Novartis's Reclast Receives FDA Approval FOR Women With Postmenopausal Osteoporosis | publisher = FierceBiotech, A Division of Questex A FierceMarkets Publication | date = August 20, 2007 | access-date = 2018-03-27}}</ref><ref name="black">{{cite journal | vauthors = Black DM, Delmas PD, Eastell R, Reid IR, Boonen S, Cauley JA, Cosman F, Lakatos P, Leung PC, Man Z, Mautalen C, Mesenbrink P, Hu H, Caminis J, Tong K, Rosario-Jansen T, Krasnow J, Hue TF, Sellmeyer D, Eriksen EF, Cummings SR | display-authors = 6 | title = Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis | journal = The New England Journal of Medicine | volume = 356 | issue = 18 | pages = 1809–1822 | date = May 2007 | pmid = 17476007 | doi = 10.1056/nejmoa067312 | s2cid = 71443125 | doi-access = free }}</ref>

===Other===

Zoledronic acid may be used for treatment of [[osteogenesis imperfecta]].<ref>{{cite journal | vauthors = Dwan K, Phillipi CA, Steiner RD, Basel D | title = Bisphosphonate therapy for osteogenesis imperfecta | journal = The Cochrane Database of Systematic Reviews | volume = 2016 | issue = 10 | pages = CD005088 | date = October 2016 | pmid = 27760454 | pmc = 6611487 | doi = 10.1002/14651858.CD005088.pub4 }}</ref>

A single 5&nbsp;mg dose of zoledronic acid is used for the treatment of [[Paget's disease of bone|Paget's disease]].{{medcn|date=January 2014}}<ref>{{Cite web|url = http://www.rheumatology.org/Practice/Clinical/Patients/Diseases_And_Conditions/Paget_s_Disease_of_Bone/|website = www.rheumatology.org|access-date = 2015-07-09|title=Paget's Disease of Bone}}</ref>


==Contraindications==
==Contraindications==
*Poor renal function (e.g. [[renal function|CrCl]]<30 mL/min)<ref>{{cite journal | last1 = Vondracek | first1 = S. F. | title = Managing osteoporosis in postmenopausal women | journal = American Journal of Health-System Pharmacy | volume = 67 | issue = 7 Suppl 3 | pages = S9 | year = 2010 | pmid = 20332498 | doi = 10.2146/ajhp100076 }}</ref>
*Poor [[kidney function]] (e.g. estimated glomerular filtration rate less than 30 mL/min)<ref>{{cite journal | vauthors = Vondracek SF | title = Managing osteoporosis in postmenopausal women | journal = American Journal of Health-System Pharmacy | volume = 67 | issue = 7 Suppl 3 | pages = S9-19 | date = April 2010 | pmid = 20332498 | doi = 10.2146/ajhp100076 }}</ref>
*[[Hypocalcaemia]]
*Hypocalcemia
*Pregnancy
*Pregnancy
*Paralysis
*Paralysis


==References==
==Side effects==
Side effects can include [[fatigue (physical)|fatigue]], [[anemia]], [[muscle pain|muscle aches]], [[fever]], and/or [[Edema|swelling]] in the feet or legs. [[Flu-like symptoms]] are common after the first infusion, although not subsequent infusions, and are thought to occur because of its potential to activate human [[γδ T cells|gamma delta T cell]] (γδ T cells).
<references/>

===Kidneys===
There is a risk of severe renal impairment. Appropriate hydration is important before administration, as is adequate [[calcium]] and [[vitamin D]] intake before Aclasta therapy in patients with [[hypocalcaemia]], and for ten days following Aclasta in patients with Paget's disease of the bone. Monitoring for other mineral metabolism disorders and the avoidance of invasive dental procedures for those who develop [[osteonecrosis of the jaw]] is recommended.<ref>{{Cite web | url=http://www.nps.org.au/__data/assets/pdf_file/0006/60945/nvcaclin.pdf | title=NPS MedicineWise | access-date=2014-01-25 | archive-url=https://web.archive.org/web/20160304042644/http://www.nps.org.au/__data/assets/pdf_file/0006/60945/nvcaclin.pdf | archive-date=2016-03-04 | url-status=dead }}</ref>

Zoledronate is rapidly processed via the [[kidney]]s; consequently its administration is not recommended for patients with reduced [[renal function]] or kidney disease.<ref>{{cite web|url=http://emc.medicines.org.uk/medicine/14062/SPC/Zometa+4mg+5ml+Concentrate+for+Solution+for+Infusion/|title=Zometa 4mg/5ml Concentrate for Solution for Infusion|work=medicines.org.uk|access-date=2010-02-24|archive-url=https://web.archive.org/web/20100224070712/http://www.emc.medicines.org.uk/medicine/14062/SPC/Zometa%204mg%205ml%20Concentrate%20for%20Solution%20for%20Infusion|archive-date=2010-02-24|url-status=dead}}</ref> Some cases of [[acute kidney injury]] either requiring dialysis or having a fatal outcome following Reclast use have been reported to the U.S. [[Food and Drug Administration]] (FDA).<ref>{{cite web|url=https://www.drugs.com/fda/reclast-zoledronic-acid-safety-communication-new-updated-warning-kidney-impairment-13020.html|title=FDA Alert: Reclast (zoledronic acid): Drug Safety Communication - New Contraindication and Updated Warning on Kidney Impairment|work=drugs.com}}</ref> This assessment was confirmed by the [[European Medicines Agency]] (EMA), whose Committee for Medicinal Products for Human Use (CHMP) specified new contraindications for the medication on 15 December 2011, which include hypocalcaemia and severe renal impairment with a [[creatinine]] clearance of less than 35 ml/min.<ref>{{cite web|url=http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/000595/smops/Positive/human_smop_000319.jsp&mid=WC0b01ac058001d127|title=European Medicines Agency - Human medicines|work=europa.eu|access-date=2012-04-03|archive-date=2015-09-25|archive-url=https://web.archive.org/web/20150925101429/http://www.ema.europa.eu/ema/index.jsp?curl=pages%2Fmedicines%2Fhuman%2Fmedicines%2F000595%2Fsmops%2FPositive%2Fhuman_smop_000319.jsp&mid=WC0b01ac058001d127|url-status=dead}}</ref>

===Bone===
====Osteonecrosis of the jaw====
A rare complication that has been recently observed in cancer patients being treated with bisphosphonates is [[osteonecrosis of the jaw]]. This has mainly been seen in patients with [[multiple myeloma]] treated with zoledronic acid who have had [[dental extraction]]s.<ref>{{cite journal | vauthors = Durie BG, Katz M, Crowley J | title = Osteonecrosis of the jaw and bisphosphonates | journal = The New England Journal of Medicine | volume = 353 | issue = 1 | pages = 99–102; discussion 99–102 | date = July 2005 | pmid = 16000365 | doi = 10.1056/NEJM200507073530120 | url = https://dipot.ulb.ac.be/dspace/bitstream/2013/357907/3/nejm200507073530120.pdf }}</ref>

====Atypical fractures====
After approving the drug on 8 July 2009, the [[European Medicines Agency]] conducted a class review of all [[bisphosphonates]], including zoledronic acid, after several cases of atypical fractures were reported.<ref name="ema.europa.eu">{{cite web|url=http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/public_health_alerts/2011/04/human_pha_detail_000027.jsp&mid=WC0b01ac058001d126|title=European Medicines Agency - Human medicines|work=europa.eu|access-date=2012-04-03|archive-date=2013-01-19|archive-url=https://web.archive.org/web/20130119221003/http://www.ema.europa.eu/ema/index.jsp?curl=pages%2Fmedicines%2Fhuman%2Fpublic_health_alerts%2F2011%2F04%2Fhuman_pha_detail_000027.jsp&mid=WC0b01ac058001d126|url-status=dead}}</ref> In 2008, the EMA's Pharmacovigilance Working Party (PhVWP) noted that [[alendronic acid]] was associated with an increased risk of atypical fracture of the [[femur]] that developed with low or no trauma. In April 2010, the PhVWP noted that further data from both the published literature and post-marketing reports were now available which suggested that atypical stress fractures of the femur may be a class effect. The [[European Medicines Agency]] then reviewed all case reports of stress fractures in patients treated with bisphosphonates, relevant data from the published literature, and data provided by the companies which market bisphosphonates. The Agency recommended that doctors who prescribe bisphosphonate-containing medicines should be aware that atypical fractures may occur rarely in the femur, especially after long-term use, and that doctors who are prescribing these medicines for the prevention or treatment of osteoporosis should regularly review the need for continued treatment, especially after five or more years of use.<ref name="ema.europa.eu"/>

==Pharmacology==
As a [[bisphosphonates#Nitrogenous|nitrogenous bisphosphonate]], zoledronic acid is a potent inhibitor of [[bone resorption]], allowing the bone-forming cells time to rebuild normal [[bone]] and allowing [[bone remodeling]].<ref>{{Cite web |url=http://www.nps.org.au/__data/assets/pdf_file/0006/60945/nvcaclin.pdf |title=Aclasta label- Australia |access-date=2014-01-25 |archive-url=https://web.archive.org/web/20160304042644/http://www.nps.org.au/__data/assets/pdf_file/0006/60945/nvcaclin.pdf |archive-date=2016-03-04 |url-status=dead }}</ref>
<ref>
{{cite web |url=https://www.osteoporosis.foundation/health-professionaBisphosphonatesls/treatment/bisphosphonates |title=Bisphosphonates |date= |website=International Osteoporosis Foundation |access-date=30 July 2022 |quote=}}
</ref>

{| class="wikitable"
|+Relative potency<ref>{{Cite book|title=Essentials of medical pharmacology | vauthors = Tripathi KD |isbn=9789350259375 |edition= Seventh|location=New Delhi | publisher = Jaypee Brothers Medical Publishers, Ltd. |oclc=868299888|date = 2013-09-30}}</ref>
!Bisphosphonate
!Relative potency
|-
|[[Etidronic acid|Etidronate]]
|1
|-
|[[Tiludronic acid|Tiludronate]]
|10
|-
|[[Pamidronic acid|Pamidronate]]
|100
|-
|[[Alendronic acid|Alendronate]]
|100-500
|-
|[[Ibandronic acid|Ibandronate]]
|500-1000
|-
|[[Risedronic acid|Risedronate]]
|1000
|-
|Zoledronate
|5000
|}

==Research==
Zoledronic acid has been found to have a direct antitumor effect and to synergistically augment the effects of other antitumor agents in [[osteosarcoma]] cells.<ref>{{cite journal | vauthors = Koto K, Murata H, Kimura S, Horie N, Matsui T, Nishigaki Y, Ryu K, Sakabe T, Itoi M, Ashihara E, Maekawa T, Fushiki S, Kubo T | display-authors = 6 | title = Zoledronic acid inhibits proliferation of human fibrosarcoma cells with induction of apoptosis, and shows combined effects with other anticancer agents | journal = Oncology Reports | volume = 24 | issue = 1 | pages = 233–239 | date = July 2010 | pmid = 20514467 | doi = 10.3892/or_00000851 | doi-access = free }}</ref>

Zoledronic acid has shown significant benefits versus placebo over three years, with a reduced number of [[vertebral fracture]]s and improved markers of bone density.<ref>{{cite journal | vauthors = Reid IR, Brown JP, Burckhardt P, Horowitz Z, Richardson P, Trechsel U, Widmer A, Devogelaer JP, Kaufman JM, Jaeger P, Body JJ, Brandi ML, Broell J, Di Micco R, Genazzani AR, Felsenberg D, Happ J, Hooper MJ, Ittner J, Leb G, Mallmin H, Murray T, Ortolani S, Rubinacci A, Saaf M, Samsioe G, Verbruggen L, Meunier PJ | display-authors = 6 | title = Intravenous zoledronic acid in postmenopausal women with low bone mineral density | journal = The New England Journal of Medicine | volume = 346 | issue = 9 | pages = 653–661 | date = February 2002 | pmid = 11870242 | doi = 10.1056/NEJMoa011807 | doi-access = free }}</ref><ref name="black"/> An annual dose of zoledronic acid may also prevent recurring fractures in patients with a previous hip fracture.<ref name="Lyles"/>

===With hormone therapy for breast cancer===
An increase in [[disease-free survival]] (DFS) was found in the ABCSG-12 trial, in which 1,803 premenopausal women with endocrine-responsive early breast cancer received [[anastrozole]] with zoledronic acid.<ref>{{cite journal | vauthors = Gnant M, Mlineritsch B, Schippinger W, Luschin-Ebengreuth G, Pöstlberger S, Menzel C, Jakesz R, Seifert M, Hubalek M, Bjelic-Radisic V, Samonigg H, Tausch C, Eidtmann H, Steger G, Kwasny W, Dubsky P, Fridrik M, Fitzal F, Stierer M, Rücklinger E, Greil R, Marth C | display-authors = 6 | title = Endocrine therapy plus zoledronic acid in premenopausal breast cancer | journal = The New England Journal of Medicine | volume = 360 | issue = 7 | pages = 679–691 | date = February 2009 | pmid = 19213681 | doi = 10.1056/NEJMoa0806285 | doi-access = free }}</ref> A retrospective analysis of the AZURE trial data revealed a DFS survival advantage, particularly where estrogen had been reduced.<ref>{{cite journal | vauthors = Coleman RE, Winter MC, Cameron D, Bell R, Dodwell D, Keane MM, Gil M, Ritchie D, Passos-Coelho JL, Wheatley D, Burkinshaw R, Marshall SJ, Thorpe H | display-authors = 6 | title = The effects of adding zoledronic acid to neoadjuvant chemotherapy on tumour response: exploratory evidence for direct anti-tumour activity in breast cancer | journal = British Journal of Cancer | volume = 102 | issue = 7 | pages = 1099–1105 | date = March 2010 | pmid = 20234364 | pmc = 2853093 | doi = 10.1038/sj.bjc.6605604 }}</ref>
In a meta-analysis of trials where upfront zoledronic acid was given to prevent [[aromatase inhibitor]]-associated bone loss, active cancer recurrence appeared to be reduced.<ref name="pmid18515735">{{cite journal | vauthors = Brufsky A, Bundred N, Coleman R, Lambert-Falls R, Mena R, Hadji P, Jin L, Schenk N, Ericson S, Perez EA | display-authors = 6 | title = Integrated analysis of zoledronic acid for prevention of aromatase inhibitor-associated bone loss in postmenopausal women with early breast cancer receiving adjuvant letrozole | journal = The Oncologist | volume = 13 | issue = 5 | pages = 503–514 | date = May 2008 | pmid = 18515735 | doi = 10.1634/theoncologist.2007-0206 | s2cid = 23710758 }}</ref>
{{as of|2010}} "The results of clinical studies of adjuvant treatment on early-stage hormone-receptor-positive breast-cancer patients under hormonal treatment – especially with the bisphosphonate zoledronic acid – caused excitement because they demonstrated an additive effect on decreasing disease relapses at bone or other sites. A number of clinical and ''in vitro'' and ''in vivo'' preclinical studies, which are either ongoing or have just ended, are investigating the mechanism of action and antitumoral activity of bisphosphonates."<ref>{{cite journal | vauthors = Tonyali O, Arslan C, Altundag K | title = The role of zoledronic acid in the adjuvant treatment of breast cancer: current perspectives | journal = Expert Opinion on Pharmacotherapy | volume = 11 | issue = 16 | pages = 2715–2725 | date = November 2010 | pmid = 20977404 | doi = 10.1517/14656566.2010.523699 | s2cid = 26073229 }}</ref>

A 2010 review concluded that "adding zoledronic acid 4 mg intravenously every 6 months to endocrine therapy in premenopausal women with hormone receptor-positive early breast cancer ... is cost-effective from a US health care system perspective".<ref>{{cite journal | vauthors = Delea TE, Taneja C, Sofrygin O, Kaura S, Gnant M | title = Cost-effectiveness of zoledronic acid plus endocrine therapy in premenopausal women with hormone-responsive early breast cancer | journal = Clinical Breast Cancer | volume = 10 | issue = 4 | pages = 267–274 | date = August 2010 | pmid = 20705558 | doi = 10.3816/CBC.2010.n.034 }}</ref>

== References ==
{{Reflist}}


==External links==
== External links ==
* {{cite web | url = https://druginfo.nlm.nih.gov/drugportal/name/zoledronic%20acid%20monohydrate | publisher = U.S. National Library of Medicine | work = Drug Information Portal | title = Zoledronic acid }}
*http://www.multiplemyeloma.org/treatments/3.06.html
*http://www.us.zometa.com/info/index.jsp
*http://www.zometa.com/index.jsp
*http://www.reclast.com/


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[[Category:Bisphosphonates]]
[[Category:Bisphosphonates]]
[[Category:Farnesyl pyrophosphate synthase inhibitors]]
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[[Category:Imidazoles]]
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[[Category:World Health Organization essential medicines]]

[[Category:Wikipedia medicine articles ready to translate]]
[[de:Zoledronat]]
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