Strontium ranelate
Clinical data | |
---|---|
Trade names | Protelos, Osseor |
AHFS/Drugs.com | UK Drug Information |
License data | |
Pregnancy category |
|
Routes of administration | By mouth |
ATC code | |
Legal status | |
Legal status |
|
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 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%) |
Identifiers | |
| |
JSmol) | |
| |
| |
(what is this?) (verify) |
Strontium ranelate, a
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.[2] 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.[3] On 21 February 2014 the European Medicine Agency recommended that strontium ranelate remain available with restrictions relative to patients with existing heart disease.[4] 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.[5] Servier ceased manufacturing the drug and in 2019, the drug returned the market in the United Kingdom under the name strontium ranelate Aristo.[6]
Uses
Strontium ranelate is registered as a prescription drug in more than 70 countries for the treatment of post-
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
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),
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.
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.[10] The most common side effects include
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 antibiotics, as these 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.[12][13]
Strontium ranelate stimulates the calcium-sensing receptors and leads to the differentiation of pre-osteoblast to
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.[15]
References
- ^ "New osteoarthritis treatments on the horizon". Harvard Women’s Health Watch. May 2013.
- ^ "IMB: Publications » Protelos (Strontium ranelate) Important Safety Information from Servier as approved by the Irish Medicines Board". Archived from the original on 2013-09-29. Retrieved 2013-06-25.
- ^ "EMA/220628/2013 PRAC recommends restriction in the use of Protelos/Osseor" (PDF). European Medicines Agency. 11 April 2013. Archived (PDF) from the original on 2019-07-05. Retrieved 2023-06-25.
- ^ "European Medicines Agency recommends that Protelos/Osseor remain available but with further restrictions". European Medicines Agency. 17 September 2018.
- .
- ^ "Strontium ranelate Aristo 2g granules for oral suspension - Summary of Product Characteristics (SMPC)". Electronic Medicines Compendium (EMC). Datapharm Ltd.
- ^ "Strontium Ranelate". NHS Choices. 4 April 2018.
- PMID 14749454.
- ^ Protelos – European Medicines Agency – Europa.eu
- ^ "Strontium ranelate: cardiovascular risk – restricted indication and new monitoring requirements Article date: March 2014". MHRA.
- ^ "Drug Safety Update". Medicines and Healthcare products Regulatory Agency. May 2012. Archived from the original on 4 June 2012. Retrieved 22 January 2013.
- PMID 18547426.
- S2CID 19175032.
- PMID 19783592.
- PMID 23117245.
External links
- "Pharma commercial intelligence, news & analysis | Evaluate". www.evaluate.com. Retrieved 2023-06-26.<
- "Servier deal "makes sense" for Osteologix". Evaluate.com. 2008-06-20. Retrieved 2023-06-26.
- EMA (2018-09-17). "PRAC recommends suspending use of Protelos/Osseor". European Medicines Agency. Retrieved 2023-06-26.
- Protelos official site Archived 2019-05-24 at the Wayback Machine
- "First Head-To-Head Study Shows That Protelos(R) (Strontium Ranelate) Builds Better Bone Than Bisphosphonate". Medical News Today. 8 December 2008. Archived from the original on 2016-03-13.