Strontium ranelate

drugbox
IUPAC_name = distrontium 5- [bis(2-oxido-2-oxoethyl)amino] -4-cyano-
3-(2-oxido-2-oxoethyl)thiophene-2-carboxylate

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CAS_number =135459-90-4
ATC_prefix = M05
ATC_suffix = BX03
PubChem = 6918182
DrugBank =
C=12|H=6|N=2|O=8|S=1|Sr=2
molecular_weight = 513.491 g/mol
bioavailability = 25% (range 19–27%)
protein_bound = 25% for plasma protein and high affinity for bone tissue
metabolism = As a divalent cation, strontium is not metabolised. Does not inhibit cytochrome P450 enzymes
elimination_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%)
pregnancy_AU =
pregnancy_US =
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.
legal_AU =
legal_UK = POM
legal_US =
legal_status =
routes_of_administration = Oral

Strontium ranelate, a strontium(II) salt of ranelic acid, is a medication for osteoporosis marketed as Protelos or Protos by Servier. It is unusual in the sense that it both increases deposition of new bone osteoblasts and reduces the resorption of bone by osteoclasts. It is therefore promoted as a "dual action bone agent" (DABA).

Mode of action

Strontium ranelate is the only antiosteoporotic agent which both increases bone formation and reduces bone resorption, resulting in a rebalance of bone turnover in favor of bone formation. Strontium ranelate significantly reduces the risk of vertebral fractures in postmenopausal osteoporotic women with or without previous fractures, and also significantly reduces the risk of hip fractures.Fact|date=July 2007

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.

Strontium ranelate is unusual in that the cation (Strontium) is responsible for the pharmacological effect, whereas in most modern medications it is the base (anion) that is the active ingredient. In early scientific pharmacology, cations such as arsenic, bismuth, mercury and lithium were frequently used but recently anions have been much more in vogue.

Indication

Strontium ranelate is registered in more than 70 countries for the treatment of post-menopausal osteoporosis to reduce the risk of vertebral and hip fractures.

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, strontium ranelate showed significant reduction in vertebral fractures with 41% and hip fractures with 36% compared with patients treated with placebo. Moreover, the efficacy sustained in 5 years data.

Furthermore, 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 antifracture efficacy in very old elderly and osteopenic patients. It is generally well tolerated.

Dosage

One sachet, containing 2 grams of strontium ranelate, daily at bedtime diluted in a glass of water.

Contradications

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 past history of VTE. Precaution is advised in patients with phenylketonuria, as strontium ranelate contains phenylalanine. Precaution as it interferes with colorimetric measurements of calcium in blood and urine.

Interactions

According to the manufacturer, strontium ranelate should be taken 2 hours apart from food, milk and derivative products, and medicinal products containing calcium. Should be taken 2 hours before antacids. Treatment should be suspended while taking oral tetracycline and quinolone antibiotics, as these chelate the active substance.

Side effects

The most common side effects include nausea, diarrhea, headache and eczema, but with only 2–4% increase compared with placebo group. However, most of the side effect will be tolerated in 3 months.

References

*National Institute for Health and Clinical Excellence. " [http://guidance.nice.org.uk/page.aspx?o=20318 Technology appraisal: Osteoporosis - primary prevention] ". Retrieved on 2007-10-27.
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External links

* [http://www.protelos.com Official site]