Strontium Ranelate

Uses and Administration

Strontium ranelate is claimed to stimulate bone formation as well as reduce bone resorption. It is used to treat severe osteoporosis ( Refer to ) in postmenopausal women at high risk of fracture and in men at increased risk of fracture. The recommended oral dose is 2 g daily, given at night and preferably at least 2 hours after food.

For details of administration in renal impairment, see Refer to .

(last reviewed 2013-09-17; last modified 2013-09-23)

References.

(last reviewed 2013-09-17; last modified 2008-07-28)

References

1. Marie PJ. Strontium ranelate: new insights into its dual mode of action.Bone. 2007; 40 5–S8. PubMed

2. Fonseca JE. Rebalancing bone turnover in favour of formation with strontium ranelate: implications for bone strength.Rheumatology (Oxford). 2008; 47 iv17–iv19. PubMed

Administration in renal impairment

Strontium excretion occurs via the kidneys and clearance decreases as creatinine clearance (CC) decreases. UK licensed product information states that no dosage adjustment of strontium ranelate is required in patients with mild to moderate renal impairment (CC 30 to 70 mL/minute). However, it is not recommended for those with severe renal impairment (CC below 30 mL/minute) because of a lack of pharmacokinetic data in these patients; continuation of treatment in patients developing severe renal impairment should be considered on an individual basis.

(last reviewed 2013-09-17; last modified 2007-07-17)

Osteoporosis

Strontium ranelate, given orally with calcium and vitamin D supplements, has been found to reduce the risk of vertebral1and non-vertebral2 fractures in postmenopausal women with osteoporosis ( Refer to ). A pooled analysis of data from these 2 studies concluded that strontium ranelate reduced both vertebral and non-vertebral fractures in patients aged 80 years or older.3 Protection against fractures was detected within 12 months, and sustained throughout 3 years of treatment. Hip fractures were also reduced over 3 years, but this did not reach statistical significance; the authors concluded that the analysis may not have been sufficiently powered in this respect. A systematic review4 concluded that while strontium ranelate reduces vertebral fractures, there is less of a reduction with non-vertebral fractures, and the effect on hip fracture remains unclear. Some have cautioned about the interpretation of bone mineral density (BMD) changes with strontium ranelate, since stronger X-ray attenuation by strontium compared with calcium must be corrected for to avoid overestimating the effect. However, increases in BMD could be useful clinically in gauging long-term compliance.5

NICE considers strontium ranelate an alternative treatment option for both primary6 and secondary7 prevention of osteoporotic fragility fractures in high-risk postmenopausal women who are unable to take a bisphosphonate. A review8 of the place of strontium ranelate in therapy considered that although it might be an alternative in patients who could not tolerate a bisphosphonate there was no convincing published evidence to support claims that it stimulated bone formation as well as reducing resorption. Further reviews4,9 concluded that additional research to confirm its mechanism of action is required and that long-term fracture data are needed, along with comparative studies evaluating the efficacy of strontium ranelate relative to other therapies such as bisphosphonates. A subsequent review10 reported that strontium ranelate reduced the risk of vertebral and nonvertebral fractures in two studies lasting 5 years and continued to provide protection against new fractures during the 3-year extensions of these studies.

Strontium ranelate has also been reported to have beneficial effects on measure of bone mineral density and markers of bone resorption in men with osteoporosis.11

(last reviewed 2013-09-17; last modified 2013-09-19)

References

1. Meunier PJ, et al.. The effects of strontium ranelate on the risk of vertebral fracture in women with postmenopausal osteoporosis.N Engl J Med. 2004; 350: 459–68. PubMed

2. Reginster JY, et al.. Strontium ranelate reduces the risk of nonvertebral fractures in postmenopausal women with osteoporosis: treatment of peripheral osteoporosis (TROPOS) study.J Clin Endocrinol Metab. 2005; 90: 2816–22. PubMed

3. Seeman E, et al.. Strontium ranelate reduces the risk of vertebral and nonvertebral fractures in women eighty years of age and older.J Bone Miner Res. 2006; 21: 1113–20. PubMed

4. O'Donnell S, et al.. Strontium ranelate for preventing and treating postmenopausal osteoporosis. Available in The Cochrane Database of Systematic Reviews; Issue 4. Chichester: John Wiley; 2006 (accessed 01/06/07). PubMed

5. Fogelman I, Blake GM. Strontium ranelate for the treatment of osteoporosis: is useful, but changes in bone mineral density need careful interpretation.BMJ. 2005; 330: 1400–1. PubMed

6. NICE. Alendronate, etidronate, risedronate, raloxifene and strontium ranelate for the primary prevention of osteoporotic fragility fractures in postmenopausal women amended: Technology Appraisal 160 (issued January 2011). Available at: Link (accessed 24/06/13)

7. NICE. Alendronate, etidronate, risedronate, raloxifene, strontium ranelate and teriparatide for the secondary prevention of osteoporotic fragility fractures in postmenopausal women amended: Technology Appraisal 161 (issued January 2011). Available at: Link (accessed 24/06/13)

8. Anonymous. Strontium ranelate for osteoporosis?Drug Ther Bull. 2006; 44: 29–32. PubMed

9. Stevenson M, et al.. The clinical effectiveness and cost-effectiveness of strontium ranelate for the prevention of osteoporotic fragility fractures in postmenopausal women.Health Technol Assess. 2007; 11: 1–134. PubMed

10. Deeks ED, Dhillon S. Strontium ranelate: a review of its use in the treatment of postmenopausal osteoporosis.Drugs. 2010; 70: 733–59. PubMed

11. Kaufman JM, et al.. Efficacy and safety of strontium ranelate in the treatment of osteoporosis in men.J Clin Endocrinol Metab. 2013; 98: 592–601. PubMed

Adverse Effects, Treatment and Precautions

Adverse Effects and Precautions

Common adverse effects of strontium ranelate include gastrointestinal disturbances, headache, dermatitis, and eczema. Disturbances in consciousness, memory loss, and seizures may occur and there have been reports of alopecia, pyrexia, confusion, peripheral oedema, and bronchial hyperreactivity.

Treatment with strontium ranelate has been associated with an increased incidence in venous thromboembolism including pulmonary embolism, and its use is contra-indicated in patients considered at risk or with a history of thromboembolic disorders. A higher risk of myocardial infarction has also been reported, and the use of strontium ranelate is contra-indicated in patients with a history of ischaemic heart disease, peripheral arterial disease, cerebrovascular disease, or uncontrolled hypertension. It should be used with caution in patients with other significant risk factors for cardiovascular events. Transient reversible increases in creatine kinase activity have been reported. Hypersensitivity reactions, including rash, pruritus, urticaria, angioedema, toxic epidermal necrolysis, and Stevens-Johnson syndrome have occurred. Drug rash with eosinophilia and systemic symptoms (DRESS), sometimes fatal, has also been reported.

Strontium may interfere with certain methods used for the determination of serum and urinary calcium.

Strontium ranelate should not be given with food or antacids—see Interactions, Refer to .

(last reviewed 2013-09-17; last modified 2013-09-18)

Alopecia

Between May 2005 and January 2008, the Spanish pharmacovigilance system received 5 reports of alopecia associated with strontium ranelate treatment.1 A causal association was suspected due to the temporal relationship between the start of treatment and the onset of alopecia, the improvement of most cases on drug withdrawal, and the exclusion of other causes. Inorganic strontium has also traditionally been a component of depilatory creams. One of the reported cases also had some features of Stevens-Johnson syndrome, and the authors suggested that alopecia may be one symptom of a more complex and severe hypersensitivity syndrome.

(last reviewed 2013-09-17; last modified 2010-07-16)

References

1. Sainz M, et al.. Strontium ranelate may cause alopecia.BMJ. 2009; 338: 1494. PubMed

Effects on the cardiovascular system

In a cohort analysis of strontium ranelate used in general practice, mainly for postmenopausal osteoporosis, there was a crude annual incidence of venous thromboembolism of 6.24 cases per 1000 patient-years exposed. This was similar to estimates in populations of similar age and in populations treated for osteoporosis. However, a history of venous thromboembolism was identified as a significant risk factor.1

(last reviewed 2013-09-17; last modified 2013-09-18)

References

1. Osborne V, et al.. Incidence of venous thromboembolism in users of strontium ranelate: an analysis of data from a prescription-event monitoring study in England.Drug Safety. 2010; 33: 579–91. PubMed

Hypersensitivity

As of November 2007, the EMEA had received reports of 16 cases of drug rash with eosinophilia and systemic symptoms (DRESS), a serious and life-threatening condition, in patients treated with strontium ranelate. Two fatalities were reported. Reactions appeared within 3 to 6 weeks of starting therapy, with skin rash, accompanied by fever, swollen glands, eosinophilia, and effects on the liver, kidneys, and lungs. Patients are advised to stop treatment with strontium ranelate if a rash occurs and to seek medical advice; treatment should not be restarted.1Similar advice, and a reminder that the drug should also be used with caution in patients with risk factors for venous thromboembolism, was issued in June 2008 by the Australian regulatory authorities; although there had been no fatalities, they had seen 16 reports of rash, one accompanied by fever and one by eosinophilia.2

(last reviewed 2013-09-17; last modified 2008-07-28)

References

1. EMEA. EMEA recommends changes in the product information for Protelos/Osseor due to the risk of severe hypersensitivity reactions (issued 16th November 2007). Available at: Link (accessed 21/01/08)

2. Adverse Drug Reactions Advisory Committee (ADRAC). Severe skin reactions and venous thromboembolism with strontium ranelate (Protos).Aust Adverse Drug React Bull. 2008; 27: 10. online

Interactions

Food, milk, and calcium-containing compounds may reduce the bioavailability of strontium ranelate; antacids containing aluminium or magnesium may reduce its absorption. Such products should be given at least 2 hours apart from, and, in the case of antacids, preferably after, strontium ranelate. Because of possible complex formation, strontium ranelate should not be given with oral tetracyclines or quinolones.

(last reviewed 2013-09-17; last modified 2008-07-28)

Pharmacokinetics

Strontium ranelate has an absolute bioavailability of about 25% after an oral dose; calcium or food reduces the bioavailability by about 60 to 70%. Peak plasma concentrations are achieved 3 to 5 hours after an oral dose. Plasma protein binding is low. Strontium ranelate has a high affinity for bone tissue. It is not metabolised, and has a half-life of about 60 hours. Excretion occurs via the kidneys and gastrointestinal tract.

(last reviewed 2013-09-17; last modified 2008-07-28)

Preparations: Single-Ingredient

The following preparations list represents a compilation of all available salt forms or related substances for this drug product.

The symbol ¤ denotes a preparation which is discontinued or no longer actively marketed.

ARGENTINA: Osteovital; Prodinam; Protos; Troncel;AUSTRALIA: Protos;AUSTRIA: Protelos;BELGIUM: Protelos¤;BRAZIL: Protos;CHILE: Protelos;CHINA: Osseor (欧思美);CZECH REPUBLIC: Osseor; Protelos;DENMARK: Protelos¤;FINLAND: Protelos;FRANCE: Protelos;GERMANY: Protelos¤;GREECE: Osseor¤; Protelos;HONG KONG: Protos;HUNGARY: Protelos;INDONESIA: Protos;IRELAND: Osseor¤; Protelos;ISRAEL: Protelos;ITALY: Osseor; Protelos;MALAYSIA: Protaxos;MEXICO: Protos;NETHERLANDS: Osseor; Protelos;NEW ZEALAND: Protos;PHILIPPINES: Protos;POLAND: Osseor; Protelos;PORTUGAL: Osseor; Protelos;RUSSIAN FEDERATION: Bivalos (Бивалос); Osteolat (Остеолат); Strometta (Строметта);SOUTH AFRICA: Protos;SINGAPORE: Protos;SPAIN: Osseor¤; Protelos¤;SWEDEN: Protelos;THAILAND: Protaxos;TURKEY: Dioss; Fixtelos; Ontiran; Protelos; Stronas; Sumilos;UNITED KINGDOM: Protelos;UKRAINE: Bivalos (Бивалос);VENEZUELA: Protelos; Serpal;

Preparations: Multi-Ingredient

The following preparations list represents a compilation of all available salt forms or related substances for this drug product.

The symbol ¤ denotes a preparation which is discontinued or no longer actively marketed.

ARGENTINA: Osteovital Plus¤;TURKEY: Fullbone D3; Stroday D3;

Therapeutic Use

• Bone Modulating Drugs

Last Updated 1/21/20