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Strontium ranelate

Strontium ranelate is an orally administered medication consisting of a strontium salt of ranelic acid, previously approved for the treatment of severe osteoporosis in postmenopausal women and adult men at high risk of fracture when other therapies were contraindicated or not tolerated.^[1] It functions as a dual-action bone agent by stimulating osteoblast-mediated bone formation and inhibiting osteoclast-driven bone resorption, thereby rebalancing bone turnover in favor of increased mineral density and improved microarchitecture without adversely affecting bone quality.^[2] Clinical trials demonstrated its efficacy in reducing vertebral fracture risk by approximately 41% and hip fracture risk by 36% over three years in postmenopausal women with osteoporosis.^[3] The standard dosage was 2 grams once daily at bedtime, dissolved in water and taken on an empty stomach to optimize absorption, with bioavailability around 25% and a plasma half-life of about 60 hours; concomitant calcium and vitamin D supplementation was recommended if dietary intake was insufficient.^[2] Common side effects included gastrointestinal disturbances such as nausea and diarrhea, while severe adverse reactions encompassed life-threatening cutaneous conditions like Stevens-Johnson syndrome and drug reaction with eosinophilia and systemic symptoms (DRESS).^[2] Of particular concern were cardiovascular risks, including an elevated incidence of myocardial infarction and venous thromboembolism, prompting restrictions on its use in patients with ischemic heart disease, peripheral arterial disease, or a history of thromboembolic events.^[1] Due to these safety issues, strontium ranelate's marketing authorization was restricted in the European Union in 2013, further restricted in 2014, and ultimately withdrawn entirely in April 2020 following a review by the European Medicines Agency that confirmed unacceptable risks outweighing benefits.^[4] It was never approved by the U.S. Food and Drug Administration and was discontinued in the EU and many regions by 2017, with production ceasing in many regions leading to shortages by 2023; although it remains available in select non-Western markets such as India and parts of Asia as of 2025, with market analyses projecting growth from USD 1.4 billion in 2023 to USD 2.1 billion by 2032, its clinical use is now obsolete in most jurisdictions.^[2]^[5]^[6]^[7]

Medical uses

Indications

Strontium ranelate was indicated for the treatment of severe osteoporosis in postmenopausal women at high risk for fractures, as well as in adult men with severe osteoporosis and a high risk of fractures, where other osteoporosis treatments are contraindicated or not tolerated.^[1] This approval was based on its demonstrated ability to reduce the risk of both vertebral and nonvertebral fractures in these high-risk populations.^[3]^[8] Pivotal clinical evidence supporting these indications comes from the Spinal Osteoporosis Therapeutic Intervention (SOTI) trial, which involved over 1,600 postmenopausal women with osteoporosis and at least one prevalent vertebral fracture; in this study, strontium ranelate 2 g daily reduced the incidence of new vertebral fractures by 41% over three years compared to placebo.^[3] Complementing this, the Treatment of Peripheral Osteoporosis (TROPOS) trial, enrolling more than 5,000 postmenopausal women with osteoporosis, showed that the same regimen decreased the risk of nonvertebral fractures by 16% over three years.^[8] These reductions were sustained without evidence of tolerance development, establishing strontium ranelate's role in fracture risk management for severe cases.^[3]^[8] The drug is not indicated for primary prevention of osteoporosis or for the management of other bone disorders, such as Paget's disease of bone, as its efficacy and safety have been evaluated specifically in severe osteoporotic populations at high fracture risk.^[1] Historically, it was positioned as a therapeutic option for patients intolerant to or contraindicated for alternative anti-osteoporosis agents, filling a niche in treatment guidelines prior to subsequent regulatory restrictions.^[1] However, following its withdrawal from the market in 2020 due to safety concerns, it is no longer used clinically in most jurisdictions.^[4]

Dosage and administration

Strontium ranelate was administered orally as granules in a sachet, with the recommended dose being 2 g once daily.^[1] The granules must be dissolved in a minimum of 30 ml of water and consumed immediately after mixing.^[1] It should be taken at bedtime, at least two hours after the last meal, to ensure optimal absorption on an empty stomach.^[1] Patients are advised to avoid consuming food, milk, or calcium-containing products for at least two hours before and after administration, as these can interfere with absorption.^[1] Treatment with strontium ranelate is intended for long-term use in managing osteoporosis, typically extending up to three to five years based on clinical trial durations, with periodic reassessment by the prescribing physician to evaluate ongoing need and efficacy.^[9]^[1] No dose adjustment is required for patients with mild to moderate renal impairment (creatinine clearance 30–70 ml/min), but it is not recommended for those with severe renal impairment (creatinine clearance <30 ml/min).^[1]

Pharmacology

Mechanism of action

Strontium ranelate, upon administration, dissociates into strontium ions and ranelic acid, with the strontium component primarily responsible for its effects on bone metabolism through a dual mechanism that concurrently stimulates osteoblast-mediated bone formation and inhibits osteoclast-driven bone resorption.^[10] This dual action helps rebalance bone remodeling in favor of net bone gain.^[11] The strontium ion acts as a partial agonist of the calcium-sensing receptor (CaSR) expressed on osteoblasts and osteoclasts, mimicking calcium to activate intracellular signaling pathways such as ERK1/2 and Wnt/β-catenin in osteoblasts, which promote their replication, differentiation, and survival, while directly inhibiting osteoclast differentiation and activity; this CaSR-mediated stimulation also upregulates osteoprotegerin (OPG) production while downregulating receptor activator of nuclear factor kappa-B ligand (RANKL) expression in osteoblasts, thereby elevating the OPG/RANKL ratio and further suppressing osteoclast function.^[12] Consequently, bone resorption is reduced without fully abolishing osteoclast function, allowing for coupled remodeling.^[13] In addition to cellular effects, strontium ions incorporate into the hydroxyapatite mineral lattice of bone, substituting for calcium due to their similar ionic radius (1.13 Å vs. 0.99 Å for Ca²⁺), which expands the crystal lattice and reduces crystallite size, enhancing bone's resistance to fracture through physicochemical stabilization.^[10] This integration contributes to the anti-resorptive properties by altering the bone matrix's solubility and turnover dynamics.^[14] Preclinical studies in ovariectomized rat and monkey models of osteoporosis have shown that strontium ranelate administration (doses of 225–900 mg/kg/day) increases bone mineral density (BMD) by up to 10–15% in trabecular bone after 4–6 months, primarily through enhanced osteoblast-driven collagen type I synthesis and matrix mineralization.^[11] These effects are accompanied by decreased serum levels of the resorption marker C-terminal cross-linking telopeptide of type I collagen (CTX) by approximately 20–30% and modest changes in the formation marker procollagen type I N-terminal propeptide (P1NP), indicating reduced overall bone turnover with a bias toward formation.^[15] Strontium ranelate does not exhibit direct analgesic or anti-inflammatory effects independent of its bone-modifying actions.^[10]

Pharmacokinetics

Strontium ranelate is administered orally as granules, with absorption occurring primarily in the gastrointestinal tract. The absolute bioavailability of the strontium component is approximately 25% after a 2 g dose, with peak plasma concentrations (C_max) reached at 3 to 5 hours post-administration (T_max).^[16] Food intake, particularly calcium-rich meals, significantly reduces strontium absorption by 60% to 70% compared to fasting conditions, emphasizing the recommendation for bedtime dosing at least two hours after eating to optimize bioavailability.^[17] Following absorption, strontium ranelate distributes widely, with a steady-state volume of distribution (V_ss) of approximately 1 L/kg and low plasma protein binding of 25%. The strontium ion exhibits high affinity for bone tissue, where it preferentially accumulates in areas of active bone formation, replacing calcium in the hydroxyapatite lattice; up to 99% of absorbed strontium may deposit in bone, leading to gradual accumulation over years of treatment without significant buildup in non-calcified tissues.^[18] The ranelate moiety is not metabolized and is rapidly eliminated unchanged, while strontium itself, as a divalent cation, undergoes no metabolic transformation.^[16] Excretion of strontium ranelate occurs mainly through the kidneys, accounting for about 50% of the absorbed dose, with the remainder via the gastrointestinal tract; plasma clearance is approximately 12 mL/min, and renal clearance is 7 mL/min. The effective plasma half-life of strontium is around 60 hours, with steady-state concentrations achieved after about two weeks of daily dosing, though bone-retained strontium is released slowly, with whole-body retention persisting for years (e.g., 11% of a dose retained after three years).^[18] No dose adjustment is required for mild to moderate renal impairment (creatinine clearance 30–70 mL/min), as exposure increases by only about 30%, but the drug is contraindicated in severe renal impairment.^[16] In special populations, pharmacokinetics show minimal changes with age, body weight, or hepatic function, though elderly patients may experience slightly higher exposure due to potential declines in renal function. Gender differences are negligible, with similar bioavailability in postmenopausal women (25%) and young males (27%).^[16]

Safety profile

Adverse effects

Strontium ranelate is associated with a range of adverse effects, categorized by frequency based on clinical trials and post-marketing surveillance data. Very common adverse effects (≥1/10) include hypersensitivity skin reactions such as rash, pruritus, urticaria, and angioedema, as well as musculoskeletal pain encompassing muscle spasms, myalgia, bone pain, and arthralgia.^[1] Common adverse effects (≥1/100 to <1/10) encompass gastrointestinal disturbances like nausea and diarrhea, headache, dizziness, vertigo, and increased serum creatinine levels due to analytical interference by strontium in certain assays, which can lead to falsely elevated readings without reflecting true renal impairment.^[1] Serious adverse effects include cardiovascular risks. A pooled analysis of randomized trials reported a 1.6-fold increased odds ratio (OR 1.60, 95% CI 1.07-2.38) for myocardial infarction with strontium ranelate compared to placebo, with annual incidences of 5.7 versus 3.6 per 1,000 patient-years.^[19] Venous thromboembolism (VTE) risk is also elevated, with a relative risk of 1.4 (annual incidence 8.5 versus 5.9 per 1,000 patient-years in trials) and post-marketing reports confirming an incidence of 0.14 per 1,000 patient-years.^[20] Cutaneous reactions represent another serious concern, including drug rash with eosinophilia and systemic symptoms (DRESS), classified as rare (≥1/10,000 to <1/1,000), with a post-marketing incidence of approximately 1 per 47,000 patient-years based on 86 reported cases.^[20] DRESS typically presents with flu-like symptoms, rash, fever, eosinophilia, and organ involvement such as hepatitis.^[1] Rare and uncommon effects include seizures (uncommon, ≥1/1,000 to <1/100), liver enzyme elevations often associated with hypersensitivity reactions like hepatitis (common) or DRESS, and other events such as alopecia, confusion, and pyrexia.^[1] Long-term use leads to strontium incorporation into bone, which overestimates bone mineral density (BMD) measurements by dual-energy X-ray absorptiometry (DXA); a 1% molar replacement of calcium by strontium can cause up to a 10% overestimation due to strontium's higher X-ray attenuation.^[21] Due to cardiovascular risks, annual assessment of ischemic heart disease, peripheral arterial disease, cerebrovascular disease, or uncontrolled hypertension is recommended, with discontinuation if these develop.^[1] Treatment should be stopped immediately upon signs of severe skin reactions, VTE, or immobilization. Post-marketing surveillance up to 2017, covering over 3.4 million patient-years, reinforced these profiles without identifying new major risks beyond those from clinical trials. Patients with contraindications such as severe renal impairment (creatinine clearance <30 mL/min) are at higher risk for adverse effects and require careful monitoring.^[1]

Contraindications

Strontium ranelate is absolutely contraindicated in patients with a history of myocardial infarction, unstable angina, peripheral arterial disease, or recent cerebrovascular events, including stroke, due to an elevated risk of serious cardiovascular complications.^[1] It is also contraindicated in individuals with established, current, or past ischaemic heart disease, as well as uncontrolled hypertension, for the same reason.^[1] Severe renal impairment, defined as creatinine clearance below 30 mL/min, represents an absolute contraindication because of impaired drug clearance and potential for accumulation.^[18] Additionally, hypersensitivity to strontium ranelate or any of its excipients precludes use.^[1] Relative contraindications include active or previous venous thromboembolic events (such as deep vein thrombosis or pulmonary embolism), where the thrombotic risk may substantially outweigh benefits, and a history of transient ischemic attack, requiring careful risk-benefit assessment.^[1] Temporary or permanent immobilization, such as prolonged bed rest or post-surgical recovery, is also considered a relative contraindication due to heightened VTE risk.^[1] Strontium ranelate (pregnancy category C) is contraindicated during pregnancy because animal studies at high doses have shown reversible skeletal abnormalities in offspring, indicating potential risks to fetal bone development.^[22] It is likewise contraindicated in lactation, as physicochemical properties suggest strontium excretion into human milk, potentially exposing nursing infants to adverse effects.^[1] Pediatric use of strontium ranelate is not indicated, as safety and efficacy have not been established in children or adolescents under 18 years of age.^[1]

Drug interactions

Strontium ranelate's bioavailability is significantly reduced by approximately 60-70% when co-administered with food, milk, or medicinal products containing calcium, necessitating administration at bedtime on an empty stomach, at least two hours after eating or taking calcium supplements.^[1] Similarly, antacids containing aluminum or magnesium hydroxides cause a slight decrease in strontium absorption (20-25% reduction in area under the curve), though this is generally manageable by taking antacids at least two hours after strontium ranelate or accepting concomitant bedtime intake if necessary.^[1] Concurrent use with oral tetracycline antibiotics (e.g., doxycycline) or quinolone antibiotics (e.g., ciprofloxacin) is not recommended, as strontium ranelate forms complexes that reduce the absorption of these antibiotics, potentially decreasing their efficacy; strontium ranelate should be suspended during antibiotic treatment.^[1] No clinically significant interactions have been observed with oral vitamin D supplementation, nor with commonly co-prescribed medications such as nonsteroidal anti-inflammatory drugs (NSAIDs), paracetamol, diuretics, digoxin, or statins, based on clinical trial data showing no relevant increases in blood strontium levels.^[1] Strontium ranelate exhibits low protein binding (25-30%) and is not metabolized by or an inhibitor of cytochrome P450 enzymes, resulting in minimal risk of pharmacokinetic interactions via protein displacement or CYP450-mediated pathways.^[16]^[18] Prior bisphosphonate therapy may blunt the bone mineral density response to strontium ranelate by reducing strontium uptake into bone, though this effect diminishes after six months at the spine and persists longer at the hip.^[23]

Regulatory status and history

Approvals and marketing

Strontium ranelate was developed by the French pharmaceutical company Les Laboratoires Servier and received its initial marketing authorization in the European Union on September 21, 2004, under the brand name Protelos, for the treatment of severe osteoporosis in postmenopausal women at high risk of fractures.^[4] Following the European approval, strontium ranelate was subsequently authorized in over 70 countries worldwide, including Australia where the Therapeutic Goods Administration granted registration on June 21, 2005, as well as in various regions of Asia and Latin America by 2010.^[24] The drug was marketed primarily under the brand names Protelos and Osseor, formulated as granules for oral suspension to be mixed with water prior to administration.^[1] Upon launch, Servier promoted strontium ranelate as the first dual-action bone agent, capable of both stimulating bone formation and inhibiting bone resorption in the treatment of postmenopausal osteoporosis.^[25] Annual sales of the drug reached approximately €200 million by 2010, reflecting its commercial success in the osteoporosis market during the initial years post-approval.^[24] The primary patents protecting strontium ranelate expired around 2017, after which generic versions became available in select markets, including a formulation from Aristo Pharma in some European countries.^[26]

Restrictions and withdrawal

In April 2013, the European Medicines Agency's (EMA) Committee for Medicinal Products for Human Use (CHMP) recommended restricting strontium ranelate to the treatment of severe osteoporosis in postmenopausal women and men at high risk for fracture who are unable to use other osteoporosis treatments due to contraindications or intolerance, and specifically excluding patients with a history of or current ischemic heart disease, peripheral arterial disease, uncontrolled hypertension, or cerebrovascular disease.^[27] This decision followed a pre-specified review of randomized controlled trial data showing a 60% increased risk of myocardial infarction (MI) with strontium ranelate compared to placebo (relative risk 1.6).^[1] In April 2014, the EMA's CHMP further restricted the drug's use, limiting it to postmenopausal women at high risk for fracture who are unable to take other approved osteoporosis treatments, with requirements for prescribers to obtain informed patient consent acknowledging cardiovascular risks and to reassess the risk-benefit balance every six months.^[28] These measures were prompted by additional pharmacovigilance data confirming an elevated risk of serious cardiac events, including a relative risk of VTE of approximately 1.5 compared to placebo.^[29] In August 2017, Servier announced the permanent cessation of worldwide marketing and distribution for commercial reasons. Between 2017 and 2020, escalating safety concerns led to progressive withdrawals; the marketing authorization was revoked by the European Commission on April 14, 2020, at the manufacturer's request due to the unfavorable benefit-risk profile in light of post-marketing surveillance confirming the cardiovascular risks outweighed potential benefits.^[4]^[30] In the United Kingdom, similar actions followed, with a national shortage beginning in October 2023 after the manufacturer halted production due to supply chain issues with the active ingredient, and no plans for resumption.^[31] As of 2025, strontium ranelate remains unavailable in the United States, where it was never approved by the Food and Drug Administration owing to unresolved cardiovascular safety concerns.^[5] It is withdrawn in the European Union, never authorized in Canada, and severely restricted elsewhere. However, the drug continues to be available in select countries such as India and certain parts of Asia, though under heightened regulatory scrutiny. The global market for strontium ranelate is projected to be valued at approximately USD 1.4 billion in 2025 but is declining due to these regulatory curtailments and shifts toward alternative therapies.^[6]^[32]

Research

Clinical trials

The phase III Spinal Osteoporosis Therapeutic Intervention (SOTI) trial, conducted from 2001 to 2004, enrolled 1,649 postmenopausal women with osteoporosis (mean age 69 years) and randomized them to receive strontium ranelate 2 g/day or placebo for three years.^[33] The treatment significantly increased lumbar spine bone mineral density (BMD) by 14.4% compared to placebo (p < 0.001), alongside reductions in new vertebral fractures by 41% (relative risk [RR] 0.59; 95% CI 0.51–0.73; p < 0.001) and clinical vertebral fractures by 38% (RR 0.62; 95% CI 0.47–0.83; p < 0.001).^[33]^[34] The concurrent Treatment of Peripheral Osteoporosis (TROPOS) trial, spanning 2001 to 2005, involved 5,091 postmenopausal women with osteoporosis (mean age 76 years) randomized to the same regimen.^[35] Over three years, strontium ranelate reduced the risk of nonvertebral fractures by 16% (RR 0.84; 95% CI 0.70–0.995; p = 0.04) and major nonvertebral fragility fractures by 19% (RR 0.81; 95% CI 0.68–0.97; p = 0.031), with a 36% reduction in hip fractures among the high-risk subgroup (age ≥74 years and femoral neck T-score ≤ -3; RR 0.64; 95% CI 0.45–0.89; p = 0.046).^[35] A pooled analysis of the SOTI and TROPOS trials demonstrated a 31% relative risk reduction in vertebral fractures over three years (RR 0.69; 95% CI 0.59–0.81; p < 0.001) in the intent-to-treat population, though no significant benefit on overall mortality was observed.^[36] These findings established strontium ranelate's antifracture efficacy across skeletal sites, supported by its dual action on bone remodeling as detailed in the mechanism of action section. Open-label extensions of these phase III trials followed up to 1,089 participants for a total of 10 years of continuous strontium ranelate treatment, confirming sustained BMD gains with a 34.5% increase in lumbar spine BMD from baseline (p < 0.01 versus prior years).^[37] Antifracture benefits persisted, with 35% and 38% relative reductions in vertebral and nonvertebral fractures, respectively, during years 6–10 compared to FRAX-matched placebo expectations (p < 0.05), alongside a favorable cumulative safety profile.^[37] Key limitations of these trials include overestimation of BMD due to strontium's higher atomic number (Z=38) compared to calcium (Z=20), which enhances X-ray attenuation; after three years of treatment, approximately 11.2% of the observed spine BMD increase was artifactual, with 1% molar strontium substitution causing a 10% measurement bias.^[38] Additionally, the studies underrepresented diverse ethnic groups, as participants were predominantly postmenopausal white women from European centers, potentially limiting generalizability to other populations.^[33]^[35] Post-approval observational studies from 2010 to 2015, including a UK Clinical Practice Research Datalink analysis of 7,474 strontium ranelate initiators (2008–2013 data), examined cardiovascular safety and identified a high baseline prevalence of prior events (23.6%) and risk factors (45.9%) among users, such as ischemic heart disease (13.1%) and hypertension (38.5%), which prompted regulatory reviews despite no confirmed causal increase in new cardiac incidents.^[39]

Ongoing developments

Recent research has explored alternative strontium salts, such as strontium citrate and chloride, to mitigate the cardiovascular risks associated with strontium ranelate while preserving bone health benefits. A 2024 preclinical study in ovariectomized mice demonstrated that oral supplementation with strontium citrate at 7.5 mmol/L for 16 weeks increased trabecular bone mineral density by 16.5% and strontium content in bone tissue, though these effects were less pronounced compared to strontium ranelate (36.9% increase) and chloride (44.0% increase).^[40] This suggests strontium citrate may offer a milder anabolic profile suitable for osteoporosis management, potentially with reduced systemic exposure at therapeutic doses.^[40] In 2025, a Phase I clinical trial assessed the safety and pharmacokinetics of orally administered strontium L-lactate—a related citrate-like salt—in healthy adults, building on preclinical data to evaluate its potential for fracture prevention in osteoporosis.^[41] Early findings indicate good tolerability, though long-term risks such as venous thromboembolism remain unassessed in this early-phase study, supporting further investigation into non-ranelate formulations for broader clinical application.^[41] These alternatives are currently investigational and not approved for clinical use. Biomaterials research has advanced strontium delivery through localized scaffolds and implants, minimizing systemic risks like cardiac events observed with oral ranelate (e.g., 2.0% increased incidence at 2 g/day doses). A 2025 review highlights strontium-substituted bioactive glasses and hydroxyapatite cements that promote osteoblast differentiation via Runx2 upregulation and inhibit osteoclasts through OPG/RANKL pathways, enhancing fracture healing and implant osseointegration in preclinical models such as ovine critical-sized defects.^[42] These approaches achieve anabolic bone effects at the repair site while maintaining low, transitory serum strontium levels to avoid cardiovascular toxicity.^[42] Following the global withdrawal of strontium ranelate, limited ongoing availability persists in select non-Western markets, with research focusing on reformulations and targeted delivery systems; however, no large-scale commercial market growth is evident as of 2025 due to regulatory restrictions. Ongoing challenges include validating cardiovascular safety for alternative salts through long-term human trials, as preclinical data on reduced cardiac toxicity remain limited. Comparisons to established therapies like bisphosphonates and denosumab emphasize the need for head-to-head studies to confirm strontium alternatives' efficacy in fracture reduction without added risks.^[42]

References

[1]
[PDF] Protelos, INN-strontium ranelate - European Medicines Agency
In postmenopausal women, strontium ranelate reduces the risk of vertebral and hip fractures (see section. 5.1). The decision to prescribe strontium ranelate ...
[2]
Strontium ranelate: Uses, Interactions, Mechanism of Action
Oct 28, 2015 · 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 ...
[3]
The Effects of Strontium Ranelate on the Risk of Vertebral Fracture ...
Treatment of postmenopausal osteoporosis with strontium ranelate leads to early and sustained reductions in the risk of vertebral fractures.
[4]
Protelos | European Medicines Agency (EMA)
Overview. On 14 April 2020, the European Commission withdrew the marketing authorisation for Protelos (strontium ranelate) in the European Union (EU).
[5]
Rethinking the Appraisal and Approval of Drugs for Fracture ... - NIH
May 15, 2017 · Lesson 10: strontium ranelate. This drug was never approved by the FDA, but after its 2004 European “launch,” strontium flew below the radar ...
[6]
Strontium Ranelate Reduces the Risk of Nonvertebral Fractures in ...
Background: Strontium ranelate, a new oral drug shown to reduce vertebral fracture risk in postmenopausal women with osteoporosis, was studied in the Treat.
[7]
Strontium ranelate: a novel treatment for postmenopausal ... - NIH
The daily dose comes as granules in a sachet that are suspended in water and drunk usually at bedtime. The summary of product characteristics (SPC) gives a ...
[8]
A review of the latest insights into the mechanism of action of ...
Both Sr and Ca have been found to mediate key cellular functions in osteoblast and osteoclast cells. However, Sr also has an effect on cells which lack the CaSR ...
[9]
Dual effect of strontium ranelate: Stimulation of osteoblast ...
In vitro, strontium ranelate was shown to enhance osteoprogenitor cell replication and collagen synthesis in rat calvaria organ cultures and rat ...
[10]
Osteoblasts play key roles in the mechanisms of action of strontium ...
Jul 23, 2009 · A more recent approach has been adopted with the development of strontium ranelate which appears to affect both resorption and formation.Missing: synthesis preclinical
[11]
Strontium ranelate improves bone microarchitecture in osteoporosis
Sep 25, 2009 · These data suggest that the RANK/RANKL/OPG pathway is a key molecular target for the dual mode of action of strontium ranelate on bone cells.
[12]
The Influence of Strontium on Bone Tissue Metabolism and Its ...
Strontium, acting through the CaSR receptor on osteoblasts, increases production of osteoprotegerin and reduces expression of RANKL mRNA, which prevents the ...
[13]
Comparative Effects of Teriparatide and Strontium Ranelate on ...
Dec 4, 2009 · In conclusion, the changes in biochemical markers of bone formation confirmed bone-forming activity of teriparatide but not of SrR treatment.
[14]
[PDF] Protelos, INN-Strontium ranelate - European Medicines Agency
The recommended daily dose is one 2 g sachet once daily by oral administration. ... Thus, strontium ranelate should not be administered during pregnancy.
[15]
[PDF] OSSEOR, INN-strontium ranelate
Intake of strontium ranelate with calcium or food reduces the bioavailability of strontium by approximately 60-70%, compared with administration. 3 hours after ...
[16]
[PDF] Product information for strontium ranelate
Jan 7, 2013 · The absolute bioavailability of strontium is 20-25% after an oral dose of 2g strontium ranelate. Steady state is reached after two weeks of ...
[17]
Cardiovascular safety of calcium, magnesium and strontium
Feb 9, 2021 · The odds ratio for MI was 1.60 (95% CI: 1.07, 2.38) for strontium ranelate versus placebo (incidences of 1.7 versus 1.1%, respectively).Calcium · Magnesium · Strontium Ranelate
[18]
[PDF] Osseor, INN-strontium ranelate - European Medicines Agency
May 25, 2012 · Following publication of a study in France5, which identified 199 severe adverse reactions reported with strontium ranelate, of which 52% were ...
[19]
Effect of bone strontium on BMD measurements - PubMed
When some of the calcium in bone is replaced by strontium, X-ray absorptiometry measurements of BMD are overestimated because strontium attenuates X-rays more ...
[20]
[PDF] 202342Orig1s000 - accessdata.fda.gov
Jul 31, 2013 · The approved strontium ranelate product label contains a warning regarding the risk of thromboembolic events associated with the product.
[21]
The effect of prior bisphosphonate therapy on the subsequent BMD ...
Prior bisphosphonate use may blunt the bone mineral density (BMD) response to strontium ranelate by reducing strontium uptake into the bone.
[22]
A comparison of adverse event and fracture efficacy data for ... - NIH
Oct 7, 2014 · Strontium ranelate was registered for use in postmenopausal osteoporosis in Europe in 2004 on the basis of the two phase 3 trials, and ...
[23]
Strontium ranelate for osteoporosis? | Drug and Therapeutics Bulletin
Strontium ranelate (Protelos - Servier) is a new oral treatment for women with postmenopausal osteoporosis that is promoted as the first dual action bone agent.
[24]
Strontium for osteoporosis: Effectiveness, side effects, and more
Apr 22, 2024 · Strontium risks and side effects. According to a 2021 review, some research suggests an increased risk of heart attack with strontium ranelate ...What is strontium? · FDA approval · Effectiveness · Risks
[25]
[PDF] Recommendation to restrict the use of Protelos/Osseor (strontium ...
Apr 25, 2013 · Protelos/Osseor is contraindicated in patients with a current or past history of ischaemic heart disease, peripheral arterial disease, or ...
[26]
[PDF] Protelos/Osseor to remain available but with further restrictions
The European Medicines Agency has concluded its review of Protelos/Osseor and has recommended further restricting the use of the medicine to patients who ...
[27]
Incidence of venous thromboembolism in users of strontium ranelate
Jul 1, 2010 · An association between strontium ranelate and venous thromboembolism (VTE) was identified in an analysis of phase III clinical trials.Missing: risk | Show results with:risk
[28]
Shortage of strontium ranelate from October
Sep 28, 2023 · Stocks of strontium ranelate, the daily drug treatment for osteoporosis, are due to run out this October. Production has stopped due to a lack of the main ...
[29]
Strontium Ranelate (Protelos) and Osteoporosis
Mar 26, 2014 · Strontium ranelate (Protelos) is a drug approved for the treatment of osteoporosis in Europe, but not in Canada. It is effective in reducing fractures.
[30]
Strontium ranelate (Protos) and risk of adverse events
Apr 3, 2014 · Use strontium ranelate (Protos) with caution in patients with significant risk factors for cardiovascular events or venous thrombosis: ...
[31]
Strontium Ranelate Market Report | Global Forecast From 2025 To ...
In 2023, the global strontium ranelate market size is valued at approximately USD 1.4 billion, with a forecasted growth to reach USD 2.1 billion by 2032, ...End-User Analysis · Regional Outlook · Competitor Outlook
[32]
Clinical effects of strontium ranelate in women with postmenopausal ...
Strontium ranelate significantly reduces new vertebral and clinical vertebral fracture incidence in postmenopausal osteoporotic women.
[33]
A Review of Strontium Ranelate and Its Effect on DXA Scans
As the absorption of strontium ranelate is competitive with calcium, calcium supplements should be taken at a different time of day to avoid reducing ...Missing: percentage | Show results with:percentage
[34]
Strontium ranelate reduces the risk of nonvertebral fractures in ...
This study shows that strontium ranelate significantly reduces the risk of all nonvertebral and in a high-risk subgroup, hip fractures over a 3-yr period, ...Missing: SPROTT | Show results with:SPROTT
[35]
Strontium ranelate: vertebral and non-vertebral fracture risk reduction
... vertebral fractures was reduced in one year by 59% and by 32% over 3 years. For non-vertebral fractures, in the TReatment Of Peripheral OSteoporosis study ...Missing: pooled | Show results with:pooled
[36]
Maintenance of antifracture efficacy over 10 years with strontium ...
Conclusions: Long-term treatment with strontium ranelate is associated with sustained increases in BMD over 10 years, with a good safety profile. Our results ...Missing: gains | Show results with:gains
[37]
Theoretical Model for the Interpretation of BMD Scans in Patients Stopping Strontium Ranelate Treatment
### Summary: BMD Overestimation Due to Strontium's Atomic Number
[38]
History of cardiovascular events and cardiovascular risk factors ...
Nov 17, 2015 · Strontium ranelate was first approved for use in the European Union in 2004. ... European Medicines Agency Recommendation to Restrict the Use of ...
[39]
Influence of Various Strontium Formulations (Ranelate, Citrate, and ...
Apr 6, 2024 · It is forecasted that in 2025, the cost of health care for patients with OP will increase by as much as 25% [1]. Despite the ever-expanding ...2. Results · 2.4. Cancellous Bone... · 4. Materials And Methods
[40]
A Clinical Study to Assess the Safety and Pharmacokinetics of Orally Administered Strontium L-lactate in Healthy Adults
**Summary of Phase I Study on Oral Strontium Citrate**
[41]
Advances in strontium-releasing biomaterials for bone repair
Here, we provide an overview of strontium's use as a treatment for osteoporosis, and report current advances in biomaterials designed to deliver strontium ...