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{{Short description|Chemical compound}} |
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{{drugbox |
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{{Use dmy dates|date=July 2024}} |
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| verifiedrevid = 389389694 |
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{{cs1 config |name-list-style=vanc |display-authors=6}} |
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| IUPAC_name = (1-hydroxy-2-imidazol-1-yl-1-phosphono-ethyl)phosphonic acid |
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{{Drugbox |
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| Verifiedfields = changed |
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| verifiedrevid = 396274597 |
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| image = Zoledronic acid.svg |
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| image = Zoledronic acid.svg |
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| image_class = skin-invert-image |
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| image2 = Zoledronate-3D-balls.png |
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| width = 180px |
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| width = 180 |
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| alt = |
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| CASNo_Ref = {{cascite}} |
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| image2 = Zoledronic-acid-from-xtal-2003-3D-balls.png |
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| CAS_number = 118072-93-8 |
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| alt2 = |
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<!--Clinical data--> |
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| 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 | archive-date = 4 March 2016 | archive-url = https://web.archive.org/web/20160304174708/http://www.drugs.com/international/zoledronic-acid.html | url-status = live }}</ref> |
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| Drugs.com = {{drugs.com|monograph|zoledronic_acid}} |
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| MedlinePlus = a605023 |
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| DailyMedID = Zoledronic acid |
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| pregnancy_AU = B3 |
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| 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 | archive-date=16 November 2021 | archive-url=https://web.archive.org/web/20211116031757/https://www.drugs.com/pregnancy/zoledronic-acid.html | url-status=live }}</ref> |
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| pregnancy_category = |
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| routes_of_administration = ] |
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| class = ]<ref name=AHFS2017/> |
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| ATC_prefix = M05 |
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| ATC_prefix = M05 |
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| ATC_suffix = BA08 |
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| ATC_suffix = BA08 |
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| PubChem = 68740 |
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| DrugBank = APRD01294 |
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| legal_US = Rx-only |
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| legal_US_comment = <ref name="Reclast FDA label">{{cite web | title=Reclast- zoledronic acid injection, solution | website=DailyMed | date=7 July 2022 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3c79ff9c-a6f4-405d-b19c-7e473a61dedc | access-date=10 August 2024}}</ref> |
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| C = 5 |H = 10 |N = 2 |O = 7 |P = 2 |
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| legal_EU = Rx-only |
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| molecular_weight = 272.09 ]/] |
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| legal_EU_comment = <ref name="Zometa EPAR">{{cite web | title=Zometa EPAR | website=European Medicines Agency | date=20 March 2001 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/zometa | access-date=5 July 2024 | archive-date=7 June 2023 | archive-url=https://web.archive.org/web/20230607133720/https://www.ema.europa.eu/en/medicines/human/EPAR/zometa | url-status=live }} Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.</ref><ref name="Aclasta EPAR">{{cite web | title=Aclasta EPAR | website=European Medicines Agency (EMA) | date=15 April 2005 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/aclasta | access-date=10 August 2024}} Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.</ref> |
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| bioavailability = |
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<!--Pharmacokinetic data--> |
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| bioavailability = |
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| protein_bound = 22% |
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| protein_bound = 22% |
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| metabolism = Nil |
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| metabolism = Nil |
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| elimination_half-life = 146 hours |
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| elimination_half-life = 146 hours |
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| excretion = ] (partial) |
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| excretion = ] (partial) |
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| licence_EU = Reclast |
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<!--Identifiers--> |
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| licence_US = Zoledronic_acid |
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| CAS_number = 118072-93-8 |
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| pregnancy_category = D <small>(])</small> |
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| PubChem = 68740 |
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| legal_status = ℞-only <small>(U.S.)</small> |
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| IUPHAR_ligand = 3177 |
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| routes_of_administration = ] |
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| DrugBank = DB00399 |
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| ChemSpiderID = 61986 |
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| UNII_Ref = {{fdacite|correct|FDA}} |
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| UNII = 70HZ18PH24 |
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| KEGG_Ref = {{keggcite|changed|kegg}} |
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| KEGG = D08689 |
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| KEGG2_Ref = {{keggcite|changed|kegg}} |
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| KEGG2 = D01968 |
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| ChEMBL_Ref = {{ebicite|correct|EBI}} |
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| ChEMBL = 924 |
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| PDB_ligand = ZOL |
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| ChEBI = 46557 |
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| synonyms = zoledronate |
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<!--Chemical data--> |
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| IUPAC_name = bis(phosphonic acid) |
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| C=5 | H=10 | N=2 | O=7 | P=2 |
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| SMILES = O=P(O)(O)C(O)(Cn1ccnc1)P(=O)(O)O |
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| 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) |
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| StdInChIKey = XRASPMIURGNCCH-UHFFFAOYSA-N |
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}} |
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}} |
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'''Zoledronic acid''' (]) or '''zoledronate''' (marketed by ] under the trade names '''Zometa''', '''Zomera''', '''Aclasta''' and '''Reclast''') is a ]. Zometa is used to prevent ] ]s in patients with ]s such as ] and ], as well as for treating ].<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 ] of malignancy and can be helpful for treating pain from bone metastases. |
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<!-- Definition and medical uses --> |
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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> |
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'''Zoledronic acid''', also known as '''zoledronate''' and sold under the brand name '''Zometa''' among others,<ref name="PR">{{Cite press release|title=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=2 September 2021|website=FierceBiotech|date=20 August 2007|archive-date=28 March 2018|archive-url=https://web.archive.org/web/20180328102418/https://www.fiercebiotech.com/biotech/press-release-novartis-s-reclast-receives-fda-approval-for-women-postmenopausal|url-status=live}}</ref> by ] among others, is a ] used to treat a number of ]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|archive-date=15 December 2017|archive-url=https://web.archive.org/web/20171215143502/https://www.drugs.com/monograph/zoledronic-acid.html|url-status=live}}</ref> These include ], ] due to ], ] due to cancer, ]<ref name="AHFS2017" /> and ] (DMD). It is given by ].<ref name=AHFS2017/> |
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<!-- Side effects and mechanisms --> |
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Reclast is a single 5 mg infusion for the treatment of ]. In 2007, the ] (FDA) also approved Reclast for the treatment of postmenopausal ]. |
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Common side effects include ], ], ], diarrhea, and feeling tired.<ref name=AHFS2017/> Serious side effects may include ], ], and ].<ref name=AHFS2017/> Use during ] may result in harm to the baby.<ref name=AHFS2017/> It is in the ] family of medications.<ref name=AHFS2017/> It works by blocking the activity of ]s and thus decreases the breakdown of bone.<ref name=AHFS2017/> |
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<!-- History and culture --> |
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==Administration== |
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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 |access-date=2 June 2020 |archive-date=14 January 2023 |archive-url=https://web.archive.org/web/20230114101028/https://books.google.com/books?id=FjKfqkaKkAAC&pg=PA524 |url-status=live }}</ref> It is on the ].<ref name="WHO23rd">{{cite book | vauthors = ((World Health Organization)) | title = The selection and use of essential medicines 2023: web annex A: World Health Organization model list of essential medicines: 23rd list (2023) | year = 2023 | hdl = 10665/371090 | author-link = World Health Organization | publisher = World Health Organization | location = Geneva | id = WHO/MHP/HPS/EML/2023.02 | hdl-access=free }}</ref> |
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The standard dose for zoledronate is 4 mg to be infused ]ly over 15 min every 3–4 weeks in cancer patients. For Reclast a single dose of 5 mg is used for the treatment of Paget's disease. |
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==Medical uses== |
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Zoledronate has been approved as a once-yearly 5 mg infusion for treatment of osteoporosis and shown significant benefits versus placebo over three years, with a reduced number of ]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. </ref> |
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Zoledronic acid is ] for the prevention of skeletal related events (pathological fractures, spinal compression, radiation or surgery to bone, or tumor-induced hypercalcemia) in people with advanced malignancies involving bone; the treatment of adults with tumor-induced hypercalcemia (TIH).<ref name="Zometa EPAR" /> |
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Zoledronic acid is also indicated for the treatment and prevention of postmenopausal osteoporosis; the treatment to increase bone mass in men with osteoporosis; the treatment and prevention of glucocorticoid-induced osteoporosis; the treatment of Paget’s disease of bone in men and women.<ref name="Reclast FDA label" /><ref name="Aclasta EPAR" /> |
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==Side effects== |
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Side effects can include ], ], ], ], and/or ] in the feet or legs. ] are commonly experienced after the first zoledronate infusion, although not subsequent infusions, and are thought to occur because of its potential to activate human ] (gamma/delta T cells). |
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===Bone complications of cancer=== |
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Zoledronate is rapidly processed via the ]s; consequently its administration is not recommended for patients with reduced ] or kidney disease.<ref>http://emc.medicines.org.uk/medicine/14062/SPC/Zometa+4mg+5ml+Concentrate+for+Solution+for+Infusion/</ref> |
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Zoledronic acid is used to prevent ] in patients with ]s such as ] and ], as well as for treating ].<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=20 January 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=23 April 2010 }}</ref> It can also be used to treat ] of malignancy and can be helpful for treating pain from ].<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 | access-date = 10 October 2023 | archive-date = 19 June 2022 | archive-url = https://web.archive.org/web/20220619191125/http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/021223s028lbl.pdf | url-status = live }}</ref> |
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A rare complication that has been recently observed in cancer patients being treated with bisphosphonates is ]. This has mainly been seen in patients with multiple myeloma treated with zoledronate who have had ]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> |
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It can be given at home rather than in hospital. Such use has shown safety and quality-of-life benefits in people with ] 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> |
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===Osteoporosis=== |
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Zoledronic acid is used for the treatment of ] in men and post-menopausal women at increased risk of fracture.<ref>{{cite journal | vauthors = Dhillon S | title = Zoledronic Acid (Reclast, Aclasta): 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><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> |
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In 2007, the US ] (FDA) approved zoledronic acid for the treatment of postmenopausal ].<ref name="PR" /><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> |
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===Other=== |
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Zoledronic acid may be used for treatment of ].<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> |
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==Contraindications== |
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==Contraindications== |
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*Poor renal function (e.g. ]<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> |
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*Poor ] (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> |
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*] |
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*Hypocalcemia |
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*Pregnancy |
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*Pregnancy |
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*Paralysis |
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*Paralysis |
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==References== |
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==Side effects== |
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Side effects can include ], ], ], ], and/or ] in the feet or legs. ] 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). |
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<references/> |
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===Kidneys=== |
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There is a risk of severe renal impairment. Appropriate hydration is important before administration, as is adequate ] and ] intake before Aclasta therapy in patients with ], 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 ] is recommended.<ref>{{Cite web | url=http://www.nps.org.au/__data/assets/pdf_file/0006/60945/nvcaclin.pdf | title=NPS MedicineWise | access-date=25 January 2014 | archive-url=https://web.archive.org/web/20160304042644/http://www.nps.org.au/__data/assets/pdf_file/0006/60945/nvcaclin.pdf | archive-date=4 March 2016 | url-status=dead }}</ref> |
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Zoledronate is rapidly processed via the ]s; consequently its administration is not recommended for patients with reduced ] 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=24 February 2010|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=24 February 2010|url-status=dead}}</ref> Some cases of ] either requiring dialysis or having a fatal outcome following Reclast use have been reported to the U.S. ] (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|access-date=23 January 2018|archive-date=3 March 2016|archive-url=https://web.archive.org/web/20160303233016/http://www.drugs.com/fda/reclast-zoledronic-acid-safety-communication-new-updated-warning-kidney-impairment-13020.html|url-status=live}}</ref> This assessment was confirmed by the ] (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 ] 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=3 April 2012|archive-date=25 September 2015|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> |
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===Bone=== |
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====Osteonecrosis of the jaw==== |
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A rare complication that has been recently observed in cancer patients being treated with bisphosphonates is ]. This has mainly been seen in patients with ] treated with zoledronic acid who have had ]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 | access-date = 25 June 2023 | archive-date = 21 August 2023 | archive-url = https://web.archive.org/web/20230821192750/https://dipot.ulb.ac.be/dspace/bitstream/2013/357907/3/nejm200507073530120.pdf | url-status = live }}</ref> |
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====Atypical fractures==== |
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After approving the drug in July 2009, the ] conducted a class review of all ], 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=3 April 2012|archive-date=19 January 2013|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 ] was associated with an increased risk of atypical fracture of the ] 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 ] 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"/> |
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==Pharmacology== |
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As a ], zoledronic acid is a potent inhibitor of ], allowing the bone-forming cells time to rebuild normal ] and allowing ].<ref>{{Cite web |url=http://www.nps.org.au/__data/assets/pdf_file/0006/60945/nvcaclin.pdf |title=Aclasta label- Australia |access-date=25 January 2014 |archive-url=https://web.archive.org/web/20160304042644/http://www.nps.org.au/__data/assets/pdf_file/0006/60945/nvcaclin.pdf |archive-date=4 March 2016 |url-status=dead }}</ref> |
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<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= }}{{Dead link|date=July 2024 |bot=InternetArchiveBot |fix-attempted=yes }}</ref> |
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{| class="wikitable" |
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|+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 = 30 September 2013}}</ref> |
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!Bisphosphonate |
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!Relative potency |
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|] |
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|1 |
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|] |
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|10 |
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|] |
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|100 |
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|] |
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|100-500 |
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|] |
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|500-1000 |
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|] |
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|1000 |
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|Zoledronate |
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|5000 |
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==Research== |
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Zoledronic acid has been found to have a direct antitumor effect and to synergistically augment the effects of other antitumor agents in ] 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> |
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Zoledronic acid has shown significant benefits versus placebo over three years, with a reduced number of ]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"/> |
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===With hormone therapy for breast cancer=== |
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An increase in ] (DFS) was found in the ABCSG-12 trial, in which 1,803 premenopausal women with endocrine-responsive early breast cancer received ] 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> |
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In a meta-analysis of trials where upfront zoledronic acid was given to prevent ]-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> |
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{{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> |
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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> |
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==External links== |
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== References == |
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{{Reflist}} |
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*http://www.multiplemyeloma.org/treatments/3.06.html |
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*http://www.us.zometa.com/info/index.jsp |
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*http://www.zometa.com/index.jsp |
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*http://www.reclast.com/ |
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{{Bisphosphonates}} |
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{{Bisphosphonates}} |
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{{Portal bar | Medicine}} |
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{{Authority control}} |
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{{DEFAULTSORT:Zoledronic Acid}} |
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