Strontium ranelate
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Non-proprietary name | Strontium ranelate | |||||||||||||||||||||
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Molecular formula | C 12 H 6 N 2 O 8 SSr 2 | |||||||||||||||||||||
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Molar mass | 513.49 g · mol -1 | |||||||||||||||||||||
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As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions . |
Strontium ranelate , more precisely distrontium ranelate , is the strontium salt of ranelic acid and a medicinal substance for the treatment of osteoporosis . Strontium, like calcium, is built into the bones. Ranelic acid enables a high bioavailability of the strontium and has no influence on the bone metabolism itself .
Effect and areas of application
Taking strontium ranelate reduces the risk of breaking a bone in the spine or hip. This protection has been proven for women in all affected age groups after the menopause .
Strontium ranelate inhibits bone loss and at the same time increases bone formation. The effective agent is strontium, like calcium, a metal from the group of alkaline earth metals . Like this, it can be incorporated as part of the bone. Studies have shown that in osteoporosis patients the radiologically measured bone density could be increased by 6.8% when they were treated with strontium ranelate. However, about half of the increase is due to the higher atomic mass of strontium compared to the calcium contained in the bones, while the other half is a real increase in the mineral content of the bone. Clinical investigations are available over a treatment period of up to 8 years.
Ranelic acid itself is considered to be pharmacologically inactive. This organic acid is very polar and is hardly absorbed, the oral bioavailability is only about 2.5%. Ranelic acid brings about favorable pharmacokinetics and tolerability of the counterion strontium. An accumulation of ranelic acid was not observed in either animals or humans.
Side effects
Often nausea and diarrhea (7%) as well as headaches (3%) occur with strontium ranelate.
After its introduction in the EU in 2004, 16 cases of severe side effects were reported during treatment with strontium ranelate up to November 2007, 13 of them in France and 2 with fatal outcome. Thereupon the European and the French authorities ordered the inclusion of a corresponding warning in the product information. In the reactions is the so-called DRESS syndrome ( D rug R ash with E osinophilia and S ystemic S ymptoms), a serious response of the immune system that can affect one or more organs, in particular liver and kidney . According to the case reports , symptoms typical of DRESS appeared within 3 to 6 weeks after the start of therapy. This resulted in skin rashes, often accompanied by fever, lymphadenopathy (swollen lymph nodes) and an increase in lymphocytes . The lungs, liver and kidneys were also affected. In most cases, the condition improved after drug discontinuation and corticosteroid therapy initiated .
Central nervous side effects such as seizures, impaired consciousness and impaired memory are described.
There is also a known risk of potentially fatal venous thromboembolism with strontium. Protelos is therefore contraindicated in patients with a history of acute venous thromboembolism (VTE) or VTE, including deep vein thrombosis and pulmonary embolism, as well as for temporary or permanent immobilization due to postoperative or other prolonged bed rest.
In May 2013, a restriction of the indication as well as new contraindications and warnings were introduced to reduce the risk of adverse cardiac events. Cardiac safety data from randomized clinical trials of strontium ranelate in the treatment of osteoporosis have shown an increased risk of myocardial infarction but not an increased risk of mortality . Following a European risk assessment process, the European Medicines Agency (EMA) is calling for further restrictions on use of Protelos due to the increased risk of heart attacks and venous thrombosis .
In 2014, the BfArM recommended limiting its use to patients for whom no other therapy is possible. The restrictions on use due to the revised assessment of the benefit-risk ratio resulted in strontium renelate being withdrawn from the market in 2017 due to insufficient demand.
Commercial preparations
A dry oral suspension with the active ingredient strontium ranelate is approved in Europe under the trade names Protelos and Osseor for the "treatment of postmenopausal osteoporosis to reduce the risk of spinal column and hip fractures".
In August 2017, Servier withdrew the preparations from the market worldwide.
Web links
- Public Assessment Report (EPAR) of the European Medicines Agency (EMA) for: Strontium ranelate
Individual evidence
- ↑ harmonized classification for this substance . A labeling of 3- (3-cyano-4-carboxymethyl-5-carboxy-2-thienyl) -3-azapentanedioic distrontium salt in the Classification and Labeling Inventory of the European Chemicals Agency (ECHA), accessed on, is reproduced from a self-classification by the distributor July 12, 2020. There is not yet a
- ↑ EMEA recommends changes in the product information for Protelos / Osseor due to the risk of severe hypersensitivity reactions. EMEA , November 16, 2007 (PDF; 42 kB).
- ^ Strontium ranelate (Protelus). (PDF) In: Active ingredient CURRENT. National Association of Statutory Health Insurance Physicians , January 2009, accessed on May 11, 2020 .
- ^ Prophylaxis, diagnosis and therapy of OSTEOPOROSIS in postmenopausal women and men. (PDF) In: Guideline of the umbrella association of German-speaking scientific osteological societies. Umbrella Association of Osteology , 2017, accessed on May 11, 2020 .
- ↑ Rote-Hand-Brief about new contraindications for strontium ranelate (Protelos) (PDF; 1.7 MB) retrieved from the website of the Drug Commission of the German Medical Association (AkdÄ).
- ↑ Rote-Hand-Brief on the cardiac safety of strontium ranelate (Protelos) (PDF; 1.5 MB) retrieved from the website of the Drug Commission of the German Medical Association (AkdÄ).
- ↑ Medicines Agency recommends that Protelos / Osseor remain available but with further restrictions of February 21, 2014.
- ↑ Servier Germany: Information for medical / pharmaceutical professionals: New restricted indication and recommendations for controls when taking Protelos (strontium ranelate) , March 11, 2014, accessed on June 8, 2017 ( Rote-Hand-Brief ).
- ↑ a b Finally - Servier stops selling strontium ranelate ( PROTELOS ) . arznei-telegram April 7, 2017.
- ↑ Obituary for Protelus - Why did the osteoporosis drug have to go away so early? Deutsche Apotheker Zeitung 48/2017.