Strontium ranelate

Strontium ranelate

Clinical data
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.
Routes of administration	Oral
ATC code	M05BX03 (WHO)
Legal status
Legal status	UK: POM (Prescription only)
Pharmacokinetic data
Bioavailability	25% (range 19–27%)
Protein binding	25% for plasma protein and high affinity for bone tissue
Metabolism	As a divalent cation, strontium is not metabolised. Does not inhibit enzymes
Biological half-life	60 hours
Excretion	Renal and gastrointestinal. Plasma clearance is about 12 ml/min (CV 22%) and renal clearance about 7 ml/min (CV 28%)
Identifiers
IUPAC name distrontium 5-[bis(2-oxido-2-oxoethyl)amino]-4-cyano- 3-(2-oxido-2-oxoethyl)thiophene-2-carboxylate
CAS Number	135459-87-9 N
PubChem (CID)	6918182
ChemSpider	5293393 Y
UNII	04NQ160FRU N
KEGG	D08468 N
Chemical and physical data
Formula	C12H6N2O8SSr2
Molar mass	513.491 g/mol
3D model (Jmol)	Interactive image
SMILES [Sr+2].[Sr+2].O=C([O-])CN(c1sc(c(c1C#N)CC([O-])=O)C([O-])=O)CC([O-])=O
InChI InChI=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 Y Key:XXUZFRDUEGQHOV-UHFFFAOYSA-J Y
NY (what is this?)

Strontium ranelate, a strontium(II) 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. The drug is unusual in that it both increases deposition of new bone by osteoblasts and reduces the resorption of bone by osteoclasts. 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. The European Pharmacovigilance Risk Assessment Committee (PRAC) recommends restriction in the use of strontium ranelate, based on a routine benefit-risk assessment of the medicine, which included data showing an increased risk of heart problems, including heart attacks. On 21 February 2014 the European Medicine Agency recommended that strontium ranelate remain available with restrictions relative to patients with existing heart disease.

Strontium ranelate is registered as a prescription drug in more than 70 countries for the treatment of post-menopausal osteoporosis to reduce the risk of vertebral and hip fractures. In the United States, strontium ranelate is not approved by the FDA. In the United Kingdom, strontium ranelate is prescribed under the National Health Service as a medicine for the treatment of post menopausal osteoporosis.

2 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.