Wikipedia:WikiProject Chemicals/Chembox validation/VerifiedDataSandbox and Strontium ranelate: Difference between pages

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+{{short description|Chemical compound}}
-{{ambox | text = This page contains a copy of the infobox ({{tl|drugbox}}) taken from revid [{{fullurl:Strontium_ranelate|oldid=467667582}} 467667582] of page [[Strontium_ranelate]] with values updated to verified values.}}
 {{Drugbox
+| Verifiedfields = changed
-| verifiedrevid = 451925278
+| verifiedrevid = 470471557
-| IUPAC_name = distrontium&nbsp;5-[bis(2-oxido-2-oxoethyl)amino]-4-cyano-<br>3-(2-oxido-2-oxoethyl)thiophene-2-carboxylate
+| IUPAC_name = distrontium&nbsp;5-[bis(2-oxido-2-oxoethyl)amino]-4-cyano-<br />3-(2-oxido-2-oxoethyl)thiophene-2-carboxylate
 | image = Strontium ranelate.svg
 | image2 = Strontium ranelate 3D.png
 <!--Clinical data-->
-| tradename =
+| tradename = Protelos, Osseor
+| Drugs.com = {{drugs.com|UK|protelos}}
 | pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X -->
 | pregnancy_US = <!-- A / B            / C / D / X -->
 | pregnancy_category = Only intended for use in postmenopausal women, no data on exposed pregnancies. If strontium ranelate is used inadvertently during pregnancy, treatment must be stopped.
+| licence_EU = yes
 | legal_AU = <!-- Unscheduled / S2 / S3 / S4  / S8 -->
 | legal_UK = POM
 | legal_US = <!-- OTC                   / Rx-only  -->
-| routes_of_administration = Oral
+| routes_of_administration = By mouth
 <!--Pharmacokinetic data-->
@@ Line 24: / Line 27: @@
 <!--Identifiers-->
-| CAS_number_Ref = {{cascite|correct|??}}
+| CAS_number_Ref = {{cascite|changed|CAS}}
-| CAS_number = <!-- blanked - oldvalue: 135459-90-4 -->
+| CAS_number = 135459-87-9
 | ATC_prefix = M05
 | ATC_suffix = BX03
+| UNII_Ref = {{fdacite|changed|FDA}}
+| UNII = 04NQ160FRU
 | PubChem = 6918182
 | DrugBank_Ref = {{drugbankcite|correct|drugbank}}
 | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
 | ChemSpiderID = 5293393
+| KEGG_Ref = {{keggcite|changed|kegg}}
+| KEGG = D08468
 <!--Chemical data-->
 | C=12 | H=6 | N=2 | O=8 | S=1 | Sr=2
-| molecular_weight = 513.491 g/mol
 | smiles = [Sr+2].[Sr+2].O=C([O-])CN(c1sc(c(c1C#N)CC([O-])=O)C([O-])=O)CC([O-])=O
-| InChI = 1/C12H10N2O8S.2Sr/c13-2-6-5(1-7(15)16)10(12(21)22)23-11(6)14(3-8(17)18)4-9(19)20;;/h1,3-4H2,(H,15,16)(H,17,18)(H,19,20)(H,21,22);;/q;2*+2/p-4
-| InChIKey = XXUZFRDUEGQHOV-XBHQNQODAM
 | StdInChI_Ref = {{stdinchicite|correct|chemspider}}
 | StdInChI = 1S/C12H10N2O8S.2Sr/c13-2-6-5(1-7(15)16)10(12(21)22)23-11(6)14(3-8(17)18)4-9(19)20;;/h1,3-4H2,(H,15,16)(H,17,18)(H,19,20)(H,21,22);;/q;2*+2/p-4
@@ Line 44: / Line 48: @@
 | StdInChIKey = XXUZFRDUEGQHOV-UHFFFAOYSA-J
 }}
+'''Strontium ranelate''', a [[strontium|strontium(II)]] [[salt (chemistry)|salt]] of [[ranelic acid]], is a medication for [[osteoporosis]] marketed as '''Protelos''' or '''Protos''' by [[Servier]].  Studies indicate it can also slow the course of [[osteoarthritis]] of the knee.<ref>{{cite web | url = http://www.health.harvard.edu/press_releases/new-osteoarthritis-treatments-on-the-horizon | title = New osteoarthritis treatments on the horizon | date = May 2013 | work = Harvard Women’s Health Watch }}</ref> The drug is unusual in that it both increases deposition of new bone by [[osteoblast]]s and reduces the resorption of bone by [[osteoclast]]s. It is therefore promoted as a "dual action bone agent" (DABA).
+On 13 May 2013, Servier released a Direct Healthcare Professional Communication which stated that new restrictions for the use of strontium ranelate are now in place, as randomised trials have shown an increased risk of [[myocardial infarction]]. Servier states that the use is now restricted to treatment of severe osteoporosis in postmenopausal women at high risk for fracture.<ref>{{Cite web |url=http://www.imb.ie/EN/Publications/Publications/Protelos-strontium-ranelate-Important-Safety-Information-from-Servier-as-approved-by-the-Irish-Medicines-Board.aspx |title=IMB: Publications » Protelos (Strontium ranelate) Important Safety Information from Servier as approved by the Irish Medicines Board |access-date=2013-06-25 |archive-date=2013-09-29 |archive-url=https://web.archive.org/web/20130929014454/http://www.imb.ie/EN/Publications/Publications/Protelos-strontium-ranelate-Important-Safety-Information-from-Servier-as-approved-by-the-Irish-Medicines-Board.aspx |url-status=dead }}</ref> The European Pharmacovigilance Risk Assessment Committee (PRAC) recommended restriction in the use of strontium ranelate, based on a routine benefit-risk assessment of the medicine, which included data showing a possible increased risk of heart problems, including heart attacks.<ref>{{Cite web |date=11 April 2013 |title=EMA/220628/2013 PRAC recommends restriction in the use of Protelos/Osseor |url=https://www.ema.europa.eu/en/documents/medicine-qa/prac-recommends-restriction-use-protelos/osseor-questions-answers_en.pdf |url-status=live |archive-url=https://web.archive.org/web/20190705155626/https://www.ema.europa.eu/en/documents/medicine-qa/prac-recommends-restriction-use-protelos/osseor-questions-answers_en.pdf |archive-date=2019-07-05 |access-date=2023-06-25 |website=European Medicines Agency}}</ref> On 21 February 2014 the European Medicine Agency recommended that strontium ranelate remain available with restrictions relative to patients with existing heart disease.<ref>{{cite web | url=http://www.ema.europa.eu/ema/index.jsp?curl=pages/news_and_events/news/2014/02/news_detail_002031.jsp&mid=WC0b01ac058004d5c1 | title=European Medicines Agency recommends that Protelos/Osseor remain available but with further restrictions | work=European Medicines Agency | date=17 September 2018 | access-date=16 June 2015 | archive-date=19 July 2015 | archive-url=https://web.archive.org/web/20150719032426/http://www.ema.europa.eu/ema/index.jsp?curl=pages/news_and_events/news/2014/02/news_detail_002031.jsp&mid=WC0b01ac058004d5c1 | url-status=dead }}</ref>  In 2017, a large study of over 280,000 British and Spanish patients found no increased risk of venous thromboembolism in users of strontium ranelate compared to alendronate.<ref>{{Cite journal|url=https://academic.oup.com/rheumatology/article/56/suppl_2/kex062.080/4106584|journal=Rheumatology |date=April 2017 |volume=56 |issue=suppl_2 |doi=10.1093/rheumatology/kex062.080 | vauthors = Khalid S, Ali M, Hawley S, Judge A, Arden N, Van Staa T, Cooper C, Javaid M, Prieto-Alhambra D | display-authors = 6 |title=Osteoporosis and Metabolic Bone Disease080. Comparative Risk of Venous Thromboembolism Among Users of Different Anti-Osteoporosis Drugs in the UK National Health Service and in Catalonia, Spain: A Propensity-Matched Cohort Study |doi-access=free }}</ref>  Servier ceased manufacturing the drug and in 2019, the drug returned the market in the United Kingdom under the name strontium ranelate Aristo.<ref>{{Cite web|url=https://www.medicines.org.uk/emc/product/9767/smpc#gref|title = Strontium ranelate Aristo 2g granules for oral suspension - Summary of Product Characteristics (SMPC) | work = Electronic Medicines Compendium (EMC) | publisher = Datapharm Ltd }}</ref>
+== Uses ==
+Strontium ranelate is registered as a prescription drug in more than 70 countries for the treatment of post-[[menopause|menopausal]] [[osteoporosis]] to reduce the risk of vertebral and hip fractures. In the United States, strontium ranelate is not approved by the [[U.S. Food and Drug Administration|FDA]]. In the United Kingdom, strontium ranelate is prescribed under the [[National Health Service]] as a medicine for the treatment of post menopausal osteoporosis.<ref>{{cite web | url = http://www.nhs.uk/conditions/osteoporosis/Pages/Treatment.aspx | work = NHS Choices | title = Strontium Ranelate | date = 4 April 2018 }}</ref>
+major phase III clinical studies, SOTI (Spinal Osteoporosis Therapeutic Intervention) and TROPOS (Treatment of Peripheral Osteoporosis), were started in 2000 to investigate the efficacy of strontium ranelate in reducing vertebral fractures and peripheral fractures, including [[hip fractures]]. In the 3 years results, reported in 2004, strontium ranelate showed significant reduction in vertebral fractures with 41% and hip fractures with 36% compared with patients treated with placebo.<ref>{{cite journal | vauthors = Meunier PJ, Roux C, Seeman E, Ortolani S, Badurski JE, Spector TD, Cannata J, Balogh A, Lemmel EM, Pors-Nielsen S, Rizzoli R, Genant HK, Reginster JY | display-authors = 6 | title = The effects of strontium ranelate on the risk of vertebral fracture in women with postmenopausal osteoporosis | journal = The New England Journal of Medicine | volume = 350 | issue = 5 | pages = 459–468 | date = January 2004 | pmid = 14749454 | doi = 10.1056/NEJMoa022436 | hdl = 2268/7937 | doi-access = free | hdl-access = free }}</ref>
+The efficacy was sustained in 5 years data. The 5 years data confirmed that strontium ranelate can reduce the vertebral fractures significantly no matter the risk factors of the osteoporotic women have. These include their age (<70, 70–80 and >80), [[bone mineral density]] (osteoporotic and osteopenia), prevalent fractures (0 prevalent fracture, 1–2 prevalent fractures and >2 prevalent fractures), symptomatic fractures, [[body mass index]] and smoking.
+Strontium ranelate shows anti-fracture efficacy in very old elderly and osteopenic patients.
+== Contraindications ==
+Strontium ranelate is contraindicated in hypersensitivity to the active substance or to any of the excipients. It is not recommended in patients with severe renal disease, i.e. [[creatinine clearance]] below 30 mL/min due to lack of data. Precaution is advised in patients at increased risk of [[venous thromboembolism]] (VTE), including patients with a history of VTE. Precaution is advised in patients with [[phenylketonuria]], as formulations of strontium ranelate contain phenylalanine.<ref>{{Cite web |url=http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000560/WC500045525.pdf |title=Protelos – European Medicines Agency – Europa.eu |access-date=2016-05-15 |archive-date=2017-12-29 |archive-url=https://web.archive.org/web/20171229232135/http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000560/WC500045525.pdf |url-status=dead }}</ref> Precaution as it interferes with colorimetric measurements of calcium in blood and urine.
+== Side effects ==
+Available data do not show evidence of an increased cardiovascular risk in patients without established, current or past history of ischaemic heart disease, peripheral arterial disease or cerebrovascular disease, or in those without uncontrolled hypertension.  In a meta-analysis of 7,500 patients, in those with known uncontrolled or severe cardiovascular disease, strontium ranelate increased the risk of venous thromboembolism, pulmonary embolism and serious cardiovascular disorders, including myocardial infarction as compared with placebo (1.7% versus 1.1%). Its use is restricted in the UK to those without severe cardiovascular disease.<ref>{{cite web|title=Strontium ranelate: cardiovascular risk – restricted indication and new monitoring requirements Article date: March 2014|url=http://www.mhra.gov.uk/Safetyinformation/DrugSafetyUpdate/CON392870|publisher=MHRA}}</ref>
+The most common side effects include [[nausea]], [[diarrhea]], [[headache]] and [[eczema]], but with only 2–4% increase compared with placebo group. Most of those side effects resolved within 3 months. Occasional severe allergic reactions have been reported including drug rash with eosinophilia and systemic symptoms ([[DRESS syndrome]])<ref>{{cite web|title=Drug Safety Update|url=http://www.mhra.gov.uk/Safetyinformation/DrugSafetyUpdate/CON152727|publisher=Medicines and Healthcare products Regulatory Agency|access-date=22 January 2013|date=May 2012|url-status=dead|archive-url=https://web.archive.org/web/20120604034437/http://www.mhra.gov.uk/Safetyinformation/DrugSafetyUpdate/CON152727|archive-date=4 June 2012}}</ref>
+== Interactions ==
+According to the manufacturer, strontium ranelate should be taken 2 hours before antacids and 2 hours apart from food, milk and derivative products, and medicinal products containing calcium. Treatment should be suspended while taking oral [[tetracycline]] and [[quinolone antibiotic]]s, as these [[chelation|chelate]] the strontium ion.
+== Pharmacology ==
+=== Mechanism of action ===
+Strontium, which has the [[atomic number]] 38, belongs to group II in the periodic table of elements, just beneath [[calcium]]. Because its nucleus is very nearly the same size as that of calcium, the body easily takes up strontium and incorporates it into bones and tooth enamel in place of calcium. This is not a health problem, and in fact, it can provide a health benefit. For example, in clinical trials, the drug strontium ranelate was found to aid bone growth, increase bone density, and lessen vertebral, peripheral, and hip fractures in women.
+Strontium ranelate is an antiosteoporotic agent which both increases bone formation and reduces bone resorption, resulting in a rebalance of bone turnover in favor of bone formation. This is similar to the effects of choline-stabilized orthosilicic acid.<ref>{{cite journal | vauthors = Spector TD, Calomme MR, Anderson SH, Clement G, Bevan L, Demeester N, Swaminathan R, Jugdaohsingh R, Berghe DA, Powell JJ | display-authors = 6 | title = Choline-stabilized orthosilicic acid supplementation as an adjunct to calcium/vitamin D3 stimulates markers of bone formation in osteopenic females: a randomized, placebo-controlled trial | journal = BMC Musculoskeletal Disorders | volume = 9 | issue = 85 | pages = 85 | date = June 2008 | pmid = 18547426 | pmc = 2442067 | doi = 10.1186/1471-2474-9-85 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Calomme M, Geusens P, Demeester N, Behets GJ, D'Haese P, Sindambiwe JB, Van Hoof V, Vanden Berghe D | display-authors = 6 | title = Partial prevention of long-term femoral bone loss in aged ovariectomized rats supplemented with choline-stabilized orthosilicic acid | journal = Calcified Tissue International | volume = 78 | issue = 4 | pages = 227–232 | date = April 2006 | pmid = 16604283 | doi = 10.1007/s00223-005-0288-0 | s2cid = 19175032 }}</ref>
+Strontium ranelate stimulates the calcium-sensing receptors and leads to the differentiation of pre-osteoblast to [[osteoblast]] which increases the bone formation. Strontium ranelate also stimulates osteoblasts to secrete [[osteoprotegerin]] in inhibiting [[osteoclasts]] formed from pre-osteoclasts in relation to the [[RANKL]] system, which leads to the decrease of bone resorption.<ref>{{cite journal | vauthors = Hamdy NA | title = Strontium ranelate improves bone microarchitecture in osteoporosis | journal = Rheumatology | volume = 48 | pages = iv9–i13 | date = October 2009 | issue = Suppl 4 | pmid = 19783592 | doi = 10.1093/rheumatology/kep274 | doi-access = free }}</ref>
+==Research==
+A large international study, the "Strontium Ranelate Efficacy in Knee Osteoarthritis trial," or SEKOIA, reported in 2012 that the drug significantly slowed the course of knee OA compared to placebo in a double-blind randomised controlled trial. The drug reduced knee OA pain symptoms, improved function, and reduced x-ray detectable cartilage loss, as shown by reductions in joint space narrowing over three years.<ref>{{cite journal | vauthors = Reginster JY, Badurski J, Bellamy N, Bensen W, Chapurlat R, Chevalier X, Christiansen C, Genant H, Navarro F, Nasonov E, Sambrook PN, Spector TD, Cooper C | display-authors = 6 | title = Efficacy and safety of strontium ranelate in the treatment of knee osteoarthritis: results of a double-blind, randomised placebo-controlled trial | journal = Annals of the Rheumatic Diseases | volume = 72 | issue = 2 | pages = 179–186 | date = February 2013 | pmid = 23117245 | pmc = 3599139 | doi = 10.1136/annrheumdis-2012-202231 }}</ref>
+== References ==
+{{Reflist}}
+== External links ==
+*{{Cite web |title=Pharma commercial intelligence, news & analysis {{!}} Evaluate |url=https://www.evaluate.com/ |access-date=2023-06-26 |website=www.evaluate.com}}<
+*{{Cite web |date=2008-06-20 |title=Servier deal "makes sense" for Osteologix |url=https://www.evaluate.com/vantage/articles/news/servier-deal-makes-sense-osteologix |access-date=2023-06-26 |website=Evaluate.com |language=en}}
+*{{Cite web |last=EMA |date=2018-09-17 |title=PRAC recommends suspending use of Protelos/Osseor |url=https://www.ema.europa.eu/en/news/prac-recommends-suspending-use-protelososseor |access-date=2023-06-26 |website=European Medicines Agency |language=en}}
+* [http://www.protelos.com Protelos official site] {{Webarchive|url=https://web.archive.org/web/20190524154603/Protelos |date=2019-05-24 }}
+* {{cite news |title=First Head-To-Head Study Shows That Protelos(R) (Strontium Ranelate) Builds Better Bone Than Bisphosphonate |date=8 December 2008 |work=Medical News Today |url=http://www.medicalnewstoday.com/printerfriendlynews.php?newsid=132149|archive-url=https://web.archive.org/web/20160313053745/http://www.medicalnewstoday.com/releases/132149.php|archive-date=2016-03-13}}
+{{Drugs for treatment of bone diseases}}
+[[Category:Osteoporosis drugs]]
+[[Category:Strontium compounds]]