Strontium ranelate



Strontium ranelate is a medication used for the management of severe osteoporosis in high-risk postmenopausal women and adult men.

Generic Name
Strontium ranelate
DrugBank Accession Number

Strontium ranelate, a strontium (II) salt of ranelic acid, is a medication for osteoporosis. Some reports have shown that strontium ranelate can slow down the progression of osteoarthritis of the knee. This agent presents an atypical mechanism of action in which it increases deposition of new bone by osteoblasts and, simultaneously, reduces the resorption of bone by osteoclasts. It is therefore promoted as a "dual action bone agent" (DABA) indicated for use in treatment of severe osteoporosis.

Furthermore, various clinical studies demonstrate the ability of strontium ranelate to improve and strengthen intrinsic bone tissue quality and microarchitecture in osteoporosis by way of a number of cellular and microstructural changes by which anti-fracture efficacy is enhanced.

Available for prescription use for a time in some parts of the world as Protelos (strontium ranelate) 2 g granules for oral suspension by Servier, it was ultimately discontinued in 2016-2017 owing to an increased adverse cardiac effects profile along with increased risk of venous thromboembolism (VTE) and various life threatening allergic reactions.

Small Molecule
Approved, Withdrawn
Average: 513.49
Monoisotopic: 513.795712
Chemical Formula
Not Available



Strontium ranelate is therapeutically indicated for the treatment of severe osteoperosis in: a) postmenopasual women, and b) adult men, who are at high risk of fractures, for whom treatment with other medical products approved for the treatment of osteoperosis is not possible due to, for example, contraindications or intolerance. 6

In postmenopausal women, strontium ranelate can also reduce the risk of vertebral and hip fractures 6.

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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Treatment ofSevere osteoporosis••••••••••••
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In general, it is believed that strontium ranelate is capable of affecting a rebalance in bone turnover in favour of bone formation by: (1) increasing osteoblast differentiation from progenitors, osteoblast activity and survival, as well as regulating osteoblast-induced osteoclastogenesis, and (2) decreasing osteoclast differentiation and activity, as well as increasing osteoclast apoptosis 1.

It has also been shown that strontium ranelate is capable of improving and strengthening various components of overall bone tissue quality like bone mineral density and bone microarchitecture 1,2,3.

Mechanism of action

The underlying pathogenesis of osteperosis involves an imbalance between bone resorption and bone formation. Osteoclasts are a kind of differentiated or specialized bone cell that breaks down bone tissue while osteoblasts are another set of differentiated bone cells that synthesize and rebuild bone tissue. When osteoclasts degrade bone tissue faster than the osteoblasts are capable of rebuilding the bone tissue, low or inadequate bone mass density and osteoperosis can resula One of the mechanisms with which strontium ranelate is thought to act is its functionality as an agonist of the extracellular calcium sensing receptors (CaSRs) 3 of osteoblasts and osteoclasts 2. Ordinary interaction between calcium 2+ divalent cations with mature osteoclast CaSRs is known to induce osteoclast apoptosis. Subsequently, strontium 2+ divalent cations from strontium ranelate use can also bind CaSRs on osteoclasts to induce their apoptosis because of the strontium 2+ cation's close resemeblance to calcium 2+. Contact between extracelluar calcium 2+ and osteoclast CaSRs stimulates the phospholipase C (PLC) dependant breakdown of phosphatidylinositol 4,5-biphosphate (PIP2) into the two secondary messengers inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG). Whereas the calcium-CaSRs interaction then performs IP3 Adependent translocation of nuclear factor NF-kB from the cytoplasm to the nucleus in mature osteoclasts, strontium-CaSRs interactions involves a DAG-PKC beta II (protein kinase C beta II) signalling pathway for translocating NF-kB from the cytoplasm to the nucleus in an IP3-independent manner. Although the calcium 2+ and strontium 2+ mediated signalling pathways are different, both CaSR interactions induce osteoclast apoptosis and are in fact capable of potentiating each other, leading to enhanced osteoclast apoptosis and decreased bone tissue degradation 4.

At the same time, given the similarity between the calcium 2+ and strontium 2+ cations, strontium 2+ cations from strontium ranelate are seemingly also able to act as an agonist and stimulate the CaSRs on osteoblasts, possibly in tandem with various local osteoblast stimulatory growth factors like transforming growth factor β (TGF β) and/or bone morphogenetic proteins (BMPs), to stimulate cyclic D genes and early oncogenes like c-fos and egr-1 that can mediate the mitogenesis and proliferation of new or more osteoblasts 5. Moreover, although the involvement of the PLC mediated pathway may be a part of the signalling mechanism in osteoblasts following the stimulation of their CaSRs, this has not yet been fully elucidated 5.

Furthermore, strontium ranelate is also thought to be capable of stimulating osteoblasts to enhance the expression of osteoprotegerin while also concurrently reducing the expression of receptor activator of nuclear factor kappa-Β ligand (RANKL) in primary human osteoblastic cells. As osteoprotegerin can competitively bind to RANKL as a decoy receptor, which can prevent RANKL from binding to RANK, which is an activity that facilitates the signaling pathway for the differentiation and activaiton of osteoclasts. The subsequent net effect of these actions ultiamtely results in decreased osteoclastogenesis. 3

Moreover, bone biopsies obtained from patients treated with stronatium ranelate in clinical study reveal improvements in intrinsic bone tissue quality and microarchitecutre in ostepoerosis as evidenced by increased trabecular number, decreased trabecular separation, lower structure model index, and increased cortical thickness associated with a shift in trabecular structure from rod to plate like configurations compared with control patients 3.

Additionally, strontium from administered strontium ranelate is absorbed onto the crystal surface of treated bones and only slightly substitiutes for calcium in the apatite crystal of newly formed bone. As a result, there is an increased X-ray absorption of strontium as compared to calcium, which can lead to an amplification of bone mineral density (BMD) measurement by dual-proton X-ray absorptiometry. In essence, although strontium ranelate use can increase BMD some of the observations may be overestimations due to skeletal accretion of strontium in strontium ranelate treated patients 3.

Having the ability to both generate more osetoblasts and decrease the number of osteoclasts gives strontium ranelate an apparent dual mechanism of action when used to treat osteoperosis.


The absolute bioavailability of strontium is about 25% (within a range of 19-27%) after an oral dose of 2 g strontium ranelate. Maximum plasma concentrations are reached approximately 3-5 hours after a single dose of 2 g. Steady state is reached after 2 weeks of treatement. The intake of strontium ranelate with calcium or food reduces the bioavailablity of strontium ranelate by about 60-70%, compared with administration 3 hours after a meal 6.

Due to the relatively slow absorption of strontium, food and calcium intake should be avoided both before and after administration of strontium ranelate. Conversely, oral supplementation with vitamin D has no effect on strontium exposure whatsoever. 6

Volume of distribution

Strontium has a volume of distribution of about 1 L/kg 6.

Protein binding

The binding of strontium to human plasma proteins is low (25%) and strontium has a high affinity for bone tissue 6.


As a divalent cation, strontium is not metabolized 6.

Route of elimination

The elimination of strontium is time and dose independent. Strontium excretion occurs via the kidneys and the gastrointetinal. 6


The effective half-life of strontium is approximately 60 hours 6.


The plasma dclearance is about 12 ml/min and its renal clearance is about 7 ml/min 6.

Adverse Effects
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Strontium ranelate has been withdrawn worldwide owing to an increased adverse cardiac effects profile along with increased risk of venous thromboembolism (VTE) and various life threatening allergic reactions.

In pooled randomised placebo-controlled studies of post-menopausal osteoporotic patients, a significant increase in myocardial infarction has been observed in patients treated with strontium ranelate compared to placebo 6. Patients with significant risk factors for cardiovascular events (ie. hypertension, hyperlipidemia, diabetes mellitus, smoking) would be susceptible to an even higher risk of cardiac ishaemic events like myocardial infarction 6.

In phase III placebo-controlled studies, strontium ranelate treatment was associated with an increase in the annual incidence of venous thromboembolism (VTE), including pulmonary embolism. This places substantial risk on patients at risk of VTE and elderly (over 80 years) patients at risk of VTE who may be more commonly associated with illnesses or conditions leading to immobilisation 6.

Life-threatening cutaneous reactions like Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug rash with eosinophilia and systemic symptoms (DRESS) have been reported with the use of strontium ranelate. In particular, a higher incidence of such reactions has been reported in patients of Asian origin. 6

In a pooled analysis of randomised placebo-controlled studies in post-menopausal osteoporotic patients, the most common adverse reactions consisted of nausea and diarrhea 6.

Nevertheless, good tolerance was shown in a clinical study investigating the repeated administration of 4 g strontium ranelate per day over 25 days in healthy postmenopausal women Label. Single administration of doses up to 11 g in healthy young male volunteers did not cause any particular symptoms Label.

In patients with mild to moderate renal impairment (30-70 ml/min creatine clearance), strontium clearance decreases as creatinine clearance decreases (approximately 30% decrease over the creatinine clearance range 30 to 70 ml/min) and thereby induces an increase in strontium plasma levels. However, no dosage adjustment is required for patients with miod to moderate renal impairment - although no pharmacokinetic data exists for patients with severe renal impairment associated with creatinine clearance below 30 ml/min 6.

There are no data from the use of strontium ranelate in pregnant women 6.

Physico-chemical data suggests strontium ranelate can be excreted into human milk. Strontium ranelate should not be used during breastfeeding 6.

No effects were observed on male and female fertility in animal studies 6.

Not Available
Pharmacogenomic Effects/ADRs
Not Available


Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Aluminum hydroxideThe serum concentration of Strontium ranelate can be decreased when it is combined with Aluminum hydroxide.
Calcium acetateThe serum concentration of Strontium ranelate can be decreased when it is combined with Calcium acetate.
Calcium carbonateThe serum concentration of Strontium ranelate can be decreased when it is combined with Calcium carbonate.
Calcium chlorideThe serum concentration of Strontium ranelate can be decreased when it is combined with Calcium chloride.
Calcium citrateThe serum concentration of Strontium ranelate can be decreased when it is combined with Calcium citrate.
Food Interactions
  • Avoid calcium supplements/calcium rich foods. Take strontium ranelate separated from calcium-containing food and supplements.
  • Take on an empty stomach. Take strontium ranelate between meals and at least 2 hours after eating at bedtime for optimal bioavailability.


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Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
OsseorGranule2 gOralLes Laboratoires Servier2016-09-072020-05-19EU flag
OsseorGranule2 gOralLes Laboratoires Servier2016-09-072020-05-19EU flag
OsseorGranule2 gOralLes Laboratoires Servier2016-09-072020-05-19EU flag
OsseorGranule2 gOralLes Laboratoires Servier2016-09-072020-05-19EU flag
OsseorGranule2 gOralLes Laboratoires Servier2016-09-072020-05-19EU flag
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
FULLBONE D3 2 G/800 IU EFERVESAN TABLET, 30 ADETStrontium ranelate (2 g) + Cholecalciferol (800 IU)Tablet, effervescentOralNUVOMED İLAÇ SAN.TİC. A.Ş.2020-08-14Not applicableTurkey flag
FULLBONE D3 2 G/800 IU EFERVESAN TABLET, 60 ADETStrontium ranelate (2 g) + Cholecalciferol (800 IU)Tablet, effervescentOralNUVOMED İLAÇ SAN.TİC. A.Ş.2011-11-02Not applicableTurkey flag
STRODAY D3 2G/800 IU SAŞE , 28 SAŞEStrontium ranelate (2 g) + Cholecalciferol (800 IU)TabletOralNEUTEC İLAÇ SAN. TİC. A.Ş.2020-08-14Not applicableTurkey flag


ATC Codes
M05BX03 — Strontium ranelateM05BX53 — Strontium ranelate and colecalciferol
Drug Categories
Chemical TaxonomyProvided by Classyfire
This compound belongs to the class of organic compounds known as tetracarboxylic acids and derivatives. These are carboxylic acids containing exactly four carboxyl groups.
Organic compounds
Super Class
Organic acids and derivatives
Carboxylic acids and derivatives
Sub Class
Tetracarboxylic acids and derivatives
Direct Parent
Tetracarboxylic acids and derivatives
Alternative Parents
Alpha amino acids and derivatives / 3,4,5-trisubstituted-2-aminothiophenes / Thiophene carboxylic acids / Dialkylarylamines / Heteroaromatic compounds / Carboxylic acid salts / Nitriles / Carboxylic acids / Organopnictogen compounds / Organic salts
show 3 more
2-aminothiophene / 3,4,5-trisubstituted-2-aminothiophene / Alpha-amino acid or derivatives / Aromatic heteromonocyclic compound / Carbonitrile / Carbonyl group / Carboxylic acid / Carboxylic acid salt / Dialkylarylamine / Heteroaromatic compound
show 14 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
Not Available
Affected organisms
  • Humans and other mammals

Chemical Identifiers

CAS number
InChI Key
distrontium(2+) ion 5-[bis(carboxylatomethyl)amino]-3-(carboxylatomethyl)-4-cyanothiophene-2-carboxylate


General References
  1. Fonseca JE, Brandi ML: Mechanism of action of strontium ranelate: what are the facts? Clin Cases Miner Bone Metab. 2010 Jan;7(1):17-8. [Article]
  2. Stepan JJ: Strontium ranelate: in search for the mechanism of action. J Bone Miner Metab. 2013 Nov;31(6):606-12. doi: 10.1007/s00774-013-0494-1. Epub 2013 Aug 9. [Article]
  3. Hamdy NA: Strontium ranelate improves bone microarchitecture in osteoporosis. Rheumatology (Oxford). 2009 Oct;48 Suppl 4:iv9-13. doi: 10.1093/rheumatology/kep274. [Article]
  4. Hurtel-Lemaire AS, Mentaverri R, Caudrillier A, Cournarie F, Wattel A, Kamel S, Terwilliger EF, Brown EM, Brazier M: The calcium-sensing receptor is involved in strontium ranelate-induced osteoclast apoptosis. New insights into the associated signaling pathways. J Biol Chem. 2009 Jan 2;284(1):575-84. doi: 10.1074/jbc.M801668200. Epub 2008 Oct 16. [Article]
  5. Sharan K, Siddiqui JA, Swarnkar G, Chattopadhyay N: Role of calcium-sensing receptor in bone biology. Indian J Med Res. 2008 Mar;127(3):274-86. [Article]
  6. Electronic Medicines Compedium Proteos (strontium ranelate) Monograph [Link]
PubChem Compound
PubChem Substance
FDA label
Download (345 KB)
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Clinical Trials

Clinical Trials
4CompletedTreatmentCompliance / Postmenopausal Osteoporosis1
4CompletedTreatmentOsteopenia (Disorder) / Osteoporosis / Primary Hyperparathyroidism (PHPT)1
4CompletedTreatmentPostmenopausal Osteoporosis1
4RecruitingTreatmentClinical Trials / Femur; Fracture, Pertrochanteric / Fragility Fractures1


Not Available
Not Available
Dosage Forms
Tablet, effervescent
Tablet, effervescent2 g
Tablet, effervescentOral
GranuleOral2 gr
GranuleOral2 g
Granule, for solutionOral2 g
GranuleOral2.00 g
Granule, for suspensionOral2000 mg
Granule, for suspensionOral
Granule, for suspensionOral2 gr
Not Available
Not Available


Experimental Properties
Not Available
Predicted Properties
Water Solubility2.17 mg/mLALOGPS
pKa (Strongest Acidic)1.63Chemaxon
Physiological Charge-4Chemaxon
Hydrogen Acceptor Count10Chemaxon
Hydrogen Donor Count0Chemaxon
Polar Surface Area187.55 Å2Chemaxon
Rotatable Bond Count8Chemaxon
Refractivity116.34 m3·mol-1Chemaxon
Polarizability27.91 Å3Chemaxon
Number of Rings1Chemaxon
Rule of FiveNoChemaxon
Ghose FilterNoChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleNoChemaxon
Predicted ADMET Features
Not Available


Mass Spec (NIST)
Not Available
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSsplash10-03di-0000090000-c83d6fe8341a9539e345
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
DarkChem Lite v0.1.0
DarkChem Lite v0.1.0
DarkChem Lite v0.1.0

Drug created at October 28, 2015 00:06 / Updated at February 03, 2022 06:26