Clodronic acid: Difference between revisions

Clodronic acid
Clinical data
AHFS/Drugs.com	International Drug Names
ATC code	M05BA02 (WHO) ;
Legal status
Legal status	CA: ℞-only;
Identifiers
	IUPAC name (Dichloro-phosphono-methyl)phosphonic acid;
CAS Number	10596-23-3 ;
PubChem CID	25419;
DrugBank	DB00720 ;
ChemSpider	23731 ;
UNII	0813BZ6866;
KEGG	D03545 ;
ChEBI	CHEBI:110423 ;
ChEMBL	ChEMBL12318 ;
CompTox Dashboard (EPA)	DTXSID8046959 ;
ECHA InfoCard	100.031.090
Chemical and physical data
Formula	CH4Cl2O6P2
Molar mass	244.88 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES ClC(Cl)(P(=O)(O)O)P(=O)(O)O;
	InChI InChI=1S/CH4Cl2O6P2/c2-1(3,10(4,5)6)11(7,8)9/h(H2,4,5,6)(H2,7,8,9) ; Key:ACSIXWWBWUQEHA-UHFFFAOYSA-N ;
	(verify)

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Latest revision as of 14:50, 17 November 2023

Clodronic acid (INN) or clodronate disodium (Na₂CH₂Cl₂O₆P₂) (USAN) is a first generation (non-nitrogenous) bisphosphonate. It is an anti-osteoporotic drug approved for the prevention and treatment of osteoporosis in post-menopausal women and men to reduce vertebral fractures, hyperparathyroidism, hypercalcemia in malignancy, multiple myeloma and fracture related pain because of its anti-inflammatory effects shown as a reduction in inflammatory markers like IL-1β, IL-6, and TNF-α.^[1]

Medical uses

A study comparing the analgesic effect of clodronic acid versus acetaminophen in osteoporotic vertebral fractures showed that clodronic acid provided more analgesia than 3 grams/day of acetaminophen.^[2]

Clodronic acid is also used in experimental medicine to selectively deplete macrophages.

Clodronic acid is approved for human use in Canada and Australia, the United Kingdom, where it is marketed as Bonefos, Loron, Clodron and in Italy as Clasteon, Difosfonal, Osteostab and several generics. In other countries is prescribed as a bone resorption inhibitor and antihypercalcemic agent. It is not approved for use in the United States, because it has too many adverse effects.

Veterinary uses

Clodronic acid is approved for use in horses under the trade name Osphos, for treatment of bone resorptive processes of navicular syndrome. It is given by intramuscular injection at one point in time, with the total dose divided into 2-3 sites on the horse. Clinical effects (e.g. improvement of lameness) after a single treatment can be seen up to 6 months post-treatment.

Adverse effects

Clodronic acid has been shown to have several adverse effects. These include:^[3]

Signs of discomfort, agitation, or colic, usually within 2 hours of treatment.
Head shaking
Lip licking
Renal failure

References

^ Pennanen N, Lapinjoki S, Urtti A, Mönkkönen J (June 1995). "Effect of liposomal and free bisphosphonates on the IL-1 beta, IL-6 and TNF alpha secretion from RAW 264 cells in vitro". Pharmaceutical Research. 12 (6): 916–22. doi:10.1023/A:1016281608773. PMID 7667201. S2CID 46332840.
^ Rovetta G, Monteforte P, Balestra V (2000). "Intravenous clodronate for acute pain induced by osteoporotic vertebral fracture". Drugs Under Experimental and Clinical Research. 26 (1): 25–30. PMID 10761534.
^ U.S. Food and Drug Administration. "FDA Provides Equine Veterinarians with Important Information about TILDREN and OSPHOS for Navicular Syndrome in Horses". Food and Drug Administration. Retrieved 3 January 2015.

[1] Pennanen N, Lapinjoki S, Urtti A, Mönkkönen J (June 1995). "Effect of liposomal and free bisphosphonates on the IL-1 beta, IL-6 and TNF alpha secretion from RAW 264 cells in vitro". Pharmaceutical Research. 12 (6): 916–22. doi:10.1023/A:1016281608773. PMID 7667201. S2CID 46332840.

[2] Rovetta G, Monteforte P, Balestra V (2000). "Intravenous clodronate for acute pain induced by osteoporotic vertebral fracture". Drugs Under Experimental and Clinical Research. 26 (1): 25–30. PMID 10761534.

[3] U.S. Food and Drug Administration. "FDA Provides Equine Veterinarians with Important Information about TILDREN and OSPHOS for Navicular Syndrome in Horses". Food and Drug Administration. Retrieved 3 January 2015.

[1]

[2]

[3]

@@ Line 1: / Line 1: @@
+{{Short description|Chemical compound}}
-{{unreferenced|date=November 2014}}
 {{Drugbox
+| Watchedfields = changed
 | verifiedrevid = 476996903
-| IUPAC_name = (dichloro-phosphono-methyl)phosphonic acid
 | image = Clodronic acid.png
+| alt =
 <!--Clinical data-->
 | tradename =
 | Drugs.com = {{drugs.com|international|clodronic-acid}}
 | pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X -->
+| ATC_prefix = M05
-| pregnancy_US = <!-- A / B / C / D / X -->
+| ATC_suffix = BA02
 | legal_AU = <!-- Unscheduled / S2 / S4 / S8 -->
+| legal_CA          = Rx-only
+| legal_CA_comment  =
 | legal_UK = <!-- GSL / P / POM / CD -->
 | legal_US = <!-- OTC / Rx-only -->
 <!--Identifiers-->
 | CAS_number_Ref = {{cascite|correct|??}}
 | CAS_number = 10596-23-3
-| ATC_prefix = M05
-| ATC_suffix = BA02
 | PubChem = 25419
 | DrugBank_Ref = {{drugbankcite|correct|drugbank}}
@@ Line 30: / Line 35: @@
 | ChEMBL_Ref = {{ebicite|correct|EBI}}
 | ChEMBL = 12318
 <!--Chemical data-->
+| IUPAC_name = (Dichloro-phosphono-methyl)phosphonic acid
 | C=1 | H=4 | Cl=2 | O=6 | P=2
-| molecular_weight = 244.892 g/mol
 | smiles = ClC(Cl)(P(=O)(O)O)P(=O)(O)O
-| InChI = 1/CH4Cl2O6P2/c2-1(3,10(4,5)6)11(7,8)9/h(H2,4,5,6)(H2,7,8,9)
-| InChIKey = ACSIXWWBWUQEHA-UHFFFAOYAO
 | StdInChI_Ref = {{stdinchicite|correct|chemspider}}
 | StdInChI = 1S/CH4Cl2O6P2/c2-1(3,10(4,5)6)11(7,8)9/h(H2,4,5,6)(H2,7,8,9)
@@ Line 42: / Line 46: @@
 }}
-'''Clodronic acid''' ([[International Nonproprietary Name|INN]]) or '''clodronate disodium''' ([[United States Adopted Name|USAN]]) is a first generation (non-nitrogenous) [[bisphosphonate]]. It is an anti-osteoporotic drug  approved for the prevention and treatment of osteoporosis in post-menopausal women and men to reduce vertebral fractures, hyperparathyroidism, hypercalcemia in malignancy, multiple myeloma and fracture related pain because of its potent anti-inflammatory and analgesic effects shown as a reduction in inflammatory markers like IL-1β, IL-6, and TNF-alfa.
+'''Clodronic acid''' ([[International Nonproprietary Name|INN]]) or '''clodronate disodium''' (Na<sub>2</sub>CH<sub>2</sub>Cl<sub>2</sub>O<sub>6</sub>P<sub>2</sub>) ([[United States Adopted Name|USAN]]) is a first generation (non-nitrogenous) [[bisphosphonate]]. It is an anti-osteoporotic drug approved for the prevention and treatment of [[osteoporosis]] in post-menopausal women and men to reduce vertebral fractures, [[hyperparathyroidism]], [[hypercalcemia]] in malignancy, [[multiple myeloma]] and fracture related pain because of its anti-inflammatory effects shown as a reduction in inflammatory markers like [[Interleukin 1 beta|IL-1β]], [[Interleukin 6|IL-6]], and [[Tumor necrosis factor alpha|TNF-α]].<ref>{{cite journal | vauthors = Pennanen N, Lapinjoki S, Urtti A, Mönkkönen J | title = Effect of liposomal and free bisphosphonates on the IL-1 beta, IL-6 and TNF alpha secretion from RAW 264 cells in vitro | journal = Pharmaceutical Research | volume = 12 | issue = 6 | pages = 916–22 | date = June 1995 | pmid = 7667201 | doi = 10.1023/A:1016281608773 | s2cid = 46332840 }}</ref>
+== Medical uses ==
-An Italian study compared the analgesic effect of clodronic acid versus [[acetaminophen]] in rheumatic condition related pain.  Study result show a reduction in pain in favor of clodronic acid that provided more analgesia than 3 grams/day of acetaminophen. Clodronate is also used in experimental medicine to selectively deplete [[macrophages]].
+A study comparing the analgesic effect of clodronic acid versus [[acetaminophen]] in osteoporotic vertebral fractures showed that clodronic acid provided more analgesia than 3 grams/day of acetaminophen.<ref>{{cite journal | vauthors = Rovetta G, Monteforte P, Balestra V | title = Intravenous clodronate for acute pain induced by osteoporotic vertebral fracture | journal = Drugs Under Experimental and Clinical Research | volume = 26 | issue = 1 | pages = 25–30 | date = 2000 | pmid = 10761534 | doi =  }}</ref>
+Clodronic acid is also used in experimental medicine to selectively deplete [[macrophages]].
-Clodronic acid is approved for human use in Canada and Australia, the United Kingdom, where it is marketed as Bonefos, Loron, Clodron and in Italy as Clasteon, Difosfonal, Osteostab and several generics. In other countries is prescribed as a bone resorption inhibitor and antihypercalcemic agent.
+Clodronic acid is approved for human use in Canada and Australia, the United Kingdom, where it is marketed as Bonefos, Loron, Clodron and in Italy as Clasteon, Difosfonal, Osteostab and several generics. In other countries is prescribed as a bone resorption inhibitor and antihypercalcemic agent.  It is not approved for use in the United States, because it has too many adverse effects.
-==Use in equine medicine==
-Clodronic acid is approved for use in horses under the trade name Osphos, for treatment of bone resorptive processes of  [[navicular syndrome]]. It is given by intramuscular injection at one point in time, with the total dose divided into 2-3 sites on the horse. Clinical effects (e.g. improvement of lameness) after a single treatment can be seen up to 6 months post-treatment.
+==Veterinary uses==
-===Adverse reactions and contraindications===
+Clodronic acid is approved for use in horses under the trade name Osphos, for treatment of bone resorptive processes of [[navicular syndrome]]. It is given by intramuscular injection at one point in time, with the total dose divided into 2-3 sites on the horse. Clinical effects (e.g. improvement of lameness) after a single treatment can be seen up to 6 months post-treatment.
-Osphos has been shown to have several adverse effects. These include:<ref>{{cite web|last1=U.S. Food and Drug Administration.|title=FDA Provides Equine Veterinarians with Important Information about TILDREN and OSPHOS for Navicular Syndrome in Horses|website=http://www.fda.gov/AnimalVeterinary/ResourcesforYou/ucm406581.htm|accessdate=3 January 2015}}</ref>
+=== Adverse effects ===
+Clodronic acid has been shown to have several adverse effects. These include:<ref>{{cite web|last1=U.S. Food and Drug Administration.|title=FDA Provides Equine Veterinarians with Important Information about TILDREN and OSPHOS for Navicular Syndrome in Horses|website=[[Food and Drug Administration]] |url=https://www.fda.gov/AnimalVeterinary/ResourcesforYou/ucm406581.htm|access-date=3 January 2015}}</ref>
 * Signs of discomfort, agitation, or [[horse colic|colic]], usually within 2 hours of treatment.
 * Head shaking
 * Lip licking
+* [[acute kidney injury|Renal failure]]
-{{Bisphosphonates}}
 ==References==
 {{Reflist}}
+{{Bisphosphonates}}
+{{Portal bar|Chemistry}}
 [[Category:Bisphosphonates]]
 [[Category:Equine medications]]
+[[Category:Organochlorides]]
-{{musculoskeletal-drug-stub}}

v t e Drugs for treatment of bone diseases (M05)
Bisphosphonates	Nitrogenous Alendronic acid Ibandronic acid Incadronic acid Minodronic acid Neridronic acid Pamidronic acid Risedronic acid Zoledronic acid Non-nitrogenous Etidronic acid Clodronic acid Tiludronic acid
Bone morphogenetic proteins	Dibotermin alfa Eptotermin alfa
Other	Resorption inhibitor Ipriflavone Aluminium chlorohydrate Dual action bone agent Strontium ranelate RANKL inhibitor Denosumab Sclerostin inhibitor Romosozumab Cathepsin K inhibitor Odanacatib Parathyroid hormone-related protein analogues Abaloparatide Teriparatide Calcitonin Calcium Vitamin D