Use Of Strontium Ranelate Research Articles

Mineral density and chemical composition of the rats’ mandibles in experimental models of generalized periodontitis

The most severe and difficult to treat symptoms of generalized periodontitis associated with diabetes mellitus are changes in bone tissue. The aim of the research was to conduct a comparative study of the mineral density and chemical composition of the mandibular bone tissue in rats in the modeling of generalized periodontitis, which develops against the background of metabolic disorders in type 2 diabetes mellitus, and after additional use of strontium ranelate. The study was carried out on 24 white male Wistar rats weighing 230-250 g, divided into three groups, 8 animals in each (in I group streptozocin and nicotinamide were administered, in II group - additionally penicylamine, in III group – additionally strontium ranelate) and 6 intact rats were used as a control. According to data of computer tomography, it was found that in the control group the average values of the mineral density are 1450.0±125.0 HU, in I group – 1320.0±120.0 HU (p>0.05), in II group –1100.0±110.0 HU (p˂0.05), in III group –1400.0±137.0 HU (p>0.05). Thus, the most pronounced decrease in mineral density is observed in the case of the combined use of nicotinamide, streptozotocin and penicylamine, while strontium ranelate helps to normalize this indicator. According to atomic emission spectrometry, the mineralization index – the ratio of calcium / phosphorus – was 1.14 in the control group, 1.05 – in I, 1.0 – in II and 1.26 – in III. The strontium content in the samples of the III group exceeded the control values by almost two times (p˂0.001) in comparison with its significant decrease in the samples of the I and II groups (p˂0.05). An increase in the strontium content led to a decrease in the content of other elements, which is explained by the competitive substitution in apatite crystals. So, strontium ranelate activates remineralization of the bone component of the periodontium.

Implications of the use of Strontium Ranelate (SRAN) in periodontics, dental implantology, oral surgery, orthodontics and endodontics and its possibility of application as storage media for avulsed teeth

Dental avulsion is still public health problem and tooth replantation has important unsuccess rates due to root resorption. Strontium ranelate (SRAN) presents antiresorptive property on the bone tissue and stimulates bone formation. So we aimed to comprehensively review the literature to 1- understand the mechanism of action of SRAN regarding to its propaedeutic in periodontics, dental implantology, oral surgery, orthodontics and endodontics, 2- present the current scientific knowledge about the SRAN efficiency on tooth avulsion; 3- observe fails and gaps in the literature and open up for unexplored ideas for SRAN uses and applications. An electronic search was performed crossing the key words ‘strontium ranelate’, ‘periodontics’, ‘dental implantology’, ‘oral surgery’, ‘orthodontics’ and ‘endodontics’, PubMed/Medline, Lilacs and BBO electronic databases were searched for research articles, reviews of literature, animal laboratory studies and laboratory studies, which had been published in English until July 2020. Twenty-five articles fulfilled the inclusion and exclusion criteria. The available literature demonstrates that SRAN provides a really better propaedeutic on the bone tissue and that the topical applications show a lower risk of side effects. That open up new perspectives and for the use of SRAN as a potential storage media for avulsed teeth.

Correction to: Impact of risk minimisation measures on the use of strontium ranelate in Europe: a multi-national cohort study in 5 EU countries by the EU-ADR Alliance

The original version of this article, published on 26 November 2019 contained a mistake.

Impact of risk minimisation measures on the use of strontium ranelate in Europe: a multi-national cohort study in 5 EU countries by the EU-ADR Alliance

In May 2013 and March 2014, the European Medicines Agency (EMA) issued two decisions restricting the use of strontium ranelate (SR). These risk minimisation measures (RMM) introduced new contraindications and limited the indications of SR therapy. The EMA required an assessment of the impact of RMMs on the use of SR in Europe. Methods design: multi-national, multi-database cohort Setting: electronic medical record databases based on hospital (Denmark) and primary care provenance (Italy, Spain, the Netherlands, UK). the database source populations were included for population-based analyses, and SR users for patient-level analyses. New RMMs included contraindications (ischaemic heart disease, peripheral arterial disease, cerebrovascular disease, uncontrolled hypertension) and restricted SR indication to severe osteoporosis with initiation by experienced physician and not as first line anti-osteoporosis therapy. Prevalence and incidence rates of SR use in the population; prevalence of contraindications and restricted indications in SR users, plus 1-year therapy persistence. Drug use measures were calculated in three periods for comparison: reference (2004 to May 2013), transition (June 2013 to March 2014) and assessment (from April 2014 to end 2016). The study population included 143 million person-years(PY) of follow-up and 76,141 incident episodes of SR treatment. Average monthly prevalence rates of SR use dropped by 86.4% from 62.6/10,000 PY (95 CI 62.4-62.9) in the reference to 8.5 (8.5-8.6) in the assessment period. Similarly, the incidence rate of SR use fell by 97.3% from 7.4/10,000 PY (7.4-7.4) to 0.2 (0.2-0.2) between the reference and assessment period. The prevalence of any contraindication decreased, whilst the prevalence of restricted indications increased in these periods. One-year persistence decreased in the assessment compared with reference period. Our study demonstrates a substantial impact of the regulatory action to restrict use of SR in Europe: SR utilisation overall decreased strongly. The proportion of patients fulfilling the restricted indications, without contraindications, increased after the proposed RMMs.

A study of osteoprotective effect of l-arginine, l-norvaline and rosuvastatin on a model of hypoestrogen-induced osteoporosis in rats

Effect on the microcirculatory bed of the bony tissue is one of promising approaches to treatment of osteoporosis.
 Aim. To study anti-osteoporotic properties of endothelioprotectors: L-arginine, L-norvaline and rosuvastatin.
 Materials and Methods. Osteoprotective properties of L-arginine, L-norvaline and rosuvastatin, and also of a reference drug– strontium ranelate – were studied on 152 female rats of Wistar line using a model of hypoestrogen-induced osteoporosis. Anti-osteoporotic and endothelioprotective effect of the drugs were evaluated by laser dopplerflowmetry (LDF) of the proximal metaphysis of the femoral bone, morphometry of trabeculae of bone, and also by calculation of the coefficient of endothelial dysfunction.
 Results. LDF showed that maximal increase in microcirculation of the proximal metaphysis of the femoral bone, in comparison with animals with untreated osteoporosis (61.52±3.74 perfusion units, PU) was achieved with L-norvaline (115.25±5.36 PU, p<0.001) and rosuvastatin (106.57±5.22 PU, p<0.001), less expressed effect was demonstrated by L-arginine (98.10±4.48 PU, p<0.001) and a reference drug – strontium ranelate (86.49±4.99 PU). A similar tendency was observed in morphometry of trabeculae of bone: in the group with untreated osteoporosis the diameter of trabeculae was 61.68±1.24 µm, in the group with use fL-norvaline – 91.86±1.8 µm (p<0.001), in the group with use of L-arginine – 86.64±1.39 µm (p<0.001) and in the group with use of strontium ranelate – 89.08±1.09 µm.
 Conclusion. L-arginine and L-norvaline and also rosuvastatin possess the property of improving a morphofunctional condition of bone tissue and may be recommended for further preclinical study.

Treating osteoporosis.

Osteoporotic fractures are common resulting in increased morbidity and mortality. Exercise can help prevent osteoporosis. It can also benefit patients with osteoporosis, but the exercises must be tailored to the patient. Most Australians should be able to obtain adequate calcium in their diet and vitamin D from the sun. Supplements may be needed in some patients and they are recommended for use with other drugs for osteoporosis. Bisphosphonates, and in some patients denosumab, are first-line drugs for osteoporosis. Raloxifene and strontium ranelate can be considered in patients who cannot take bisphosphonates or denosumab. Teriparatide is reserved for patients with severe osteoporosis and the use of strontium ranelate is declining because of cardiovascular safety concerns.

Effects of strontium ranelate on bone mass and bone turnover in women with thalassemia major-related osteoporosis.

Subjects affected by thalassemia major (TM) often have reduced bone mass and increased fracture risk. Strontium ranelate (SrR) is an effective treatment for postmenopausal and male osteoporosis. To date, no data exist on the use of SrR in the treatment of TM-related osteoporosis. Our aim was to evaluate the effects of SrR on bone mineral density (BMD), bone turnover markers and inhibitors of Wnt signaling (sclerostin and DKK-1). Twenty-four TM osteoporotic women were randomized to receive daily SrR 2g or placebo in addition to calcium carbonate (1,000mg) and vitamin D (800IU). BMD at the lumbar spine and femoral neck, bone turnover markers (C-terminal telopeptide of procollagen type I [CTX], bone-specific alkaline phosphatase [BSAP]) and insulin-like growth factor-1 (IGF-1), sclerostin and DKK-1 were assessed at baseline and after 24months. Back pain was measured by visual analog scale (VAS) every 6 months. After 24months, TM women treated with SrR had increased their spine BMD values in comparison to baseline (p<0.05). Moreover, they also exhibited a reduction of CTX and sclerostin levels (but not DKK-1) and exhibited an increase of BSAP and IGF-1 (p<0.05); however, no significant changes were observed in the placebo group. In the SrR group, a reduction of back pain was observed after 18months in comparison to baseline (p<0.05) and after 24months in comparison to placebo (p<0.05). Our study reports for the first time the effects of SrR in the treatment of TM-related osteoporosis. SrR treatment improved BMD and normalized bone turnover markers, as well as lowering sclerostin serum levels.

Conventional medical therapy for osteoarthritis: current state of the evidence.

The incidence and prevalence of osteoarthritis at the knee, hip, and hand joints are rising. Knowledge about recent developments in the treatment of osteoarthritis is highly relevant to current medical and rheumatology practice. This review will highlight key findings from the published literature in the past 18 months, identified via a PubMed search, including the context for these studies, their key findings, and implications. Main themes from the literature covered by this article include a continued focus on acetaminophen and glucosamine-chondroitin as therapeutic agents in the medical management of osteoarthritis. In addition, there is a relatively novel focus on use of adalimumab, a tumor necrosis factor inhibitor, and on strontium ranelate, in relation to outcomes of pain and structural progression in osteoarthritic joints. Recent studies convey a continued focus on potential therapeutic benefit derived from a combination of glucosamine-chondroitin, and intrigue the reader with a focus on biologic therapy (i.e. tumor necrosis factor antagonist) for osteoarthritis, and with use of strontium ranelate as a newer agent with potential therapeutic benefit.

Australian TGA restricts use of strontium ranelate

Australian TGA restricts use of strontium ranelate

Use of strontium ranelate and risk of acute coronary syndrome: cohort study

BackgroundA recent pooled analysis of randomised trials found an increased risk of myocardial infarction with use of the antiosteoporotic drug strontium ranelate. We conducted a nationwide cohort study in Denmark,...

Use of strontium ranelate should be suspended because of heart risk

Use of strontium ranelate should be suspended because of heart risk

Ischaemic cardiac events and use of strontium ranelate in postmenopausal osteoporosis: a nested case–control study in the CPRD

SummaryWe explored the cardiac safety of the osteoporosis treatment strontium ranelate in the UK Clinical Practice Research Datalink. While known cardiovascular risk factors like obesity and smoking were associated with increased cardiac risk, use of strontium ranelate was not associated with any increase in myocardial infarction or cardiovascular death.IntroductionIt has been suggested that strontium ranelate may increase risk for cardiac events in postmenopausal osteoporosis. We set out to explore the cardiac safety of strontium ranelate in the Clinical Practice Research Datalink (CPRD) and linked datasets.MethodsWe performed a nested case–control study. Primary outcomes were first definite myocardial infarction, hospitalisation with myocardial infarction, and cardiovascular death. Cases and matched controls were nested in a cohort of women treated for osteoporosis. The association with exposure to strontium ranelate was analysed by multivariate conditional logistic regression.ResultsOf the 112,445 women with treated postmenopausal osteoporosis, 6,487 received strontium ranelate. Annual incidence rates for first definite myocardial infarction (1,352 cases), myocardial infarction with hospitalisation (1,465 cases), and cardiovascular death (3,619 cases) were 3.24, 6.13, and 14.66 per 1,000 patient-years, respectively. Obesity, smoking, and cardiovascular treatments were associated with significant increases in risk for cardiac events. Current or past use of strontium ranelate was not associated with increased risk for first definite myocardial infarction (odds ratio [OR] 1.05, 95 % confidence interval [CI] 0.68–1.61 and OR 1.12, 95 % CI 0.79–1.58, respectively), hospitalisation with myocardial infarction (OR 0.84, 95 % CI 0.54–1.30 and OR 1.17, 95 % CI 0.83–1.66), or cardiovascular death (OR 0.96, 95 % CI 0.76–1.21 and OR 1.16, 95 % CI 0.94–1.43) versus patients who had never used strontium ranelate.ConclusionsAnalysis in the CPRD did not find evidence for a higher risk for cardiac events associated with the use of strontium ranelate in postmenopausal osteoporosis.

Cardiovascular safety of strontium ranelate: real-life assessment in clinical practice

Cardiovascular safety of strontium ranelate: real-life assessment in clinical practice

Rheumatology meeting: Efficacy, safety of biologics central focus

Comparing two biologics Based on 1-year results from the AMPLE (Abatacept Versus Adalimumab Comparison in Biologic-Naive RA Subjects with Background Methotrexate) trial, Roy Fleischmann, MD, and colleagues reported that use of subcutaneous abatacept (Orencia—Bristol-Myers Squibb) or adalimumab (Humira—Abbott) resulted in comparable rates of remission in biologic-naive patients who had an inadequate response to methotrexate (abstract 1340). AMPLE is the fi rst head-to-head trial to compare the effi cacy of two different biologics for the management of RA. In this ongoing, randomized, investigator-blinded, 24-month Phase IIIb study, researchers randomized biologic-naive patients with RA who had an inadequate response to methotrexate to abatacept 125 mg weekly (n = 318) or adalimumab 40 mg biweekly (n = 328). All patients remained on a stable dose of methotrexate throughout the trial. Researchers assessed various remission criteria, including DAS28CRP (Disease Activity Score 28 Based on C-Reactive Protein), RAPID3 (Routine Assessment of Patient Index Data 3), CDAI (Clinical Disease Activity Index), and SDAI (Simple Disease Activity Index). After 12 months, clinical, functional, and radiographic effi cacy, and safety were similar between the two groups. The proportion of patients meeting the various remission criteria for abatacept and adalimumab were 43.3% versus 41.9% for DAS28-CRP ≤ 2.6, 27.2% versus 25.1% for RAPID3 < 1.0, 23.5% versus 24.0% for CDAI ≤ 2.8, and 23.3% versus 24.8% for SDAI ≤ 3.3. Across all assessed remission criteria, 76% to 85% of patients in both treatment arms achieved Health Assessment Questionnaire response at year 1. In addition, 63% to 100% of patients had no radiographic progression, depending on the remission criteria employed.

A large prospective European cohort study of patients treated with strontium ranelate and followed up over 3 years

Strontium ranelate has been available as an osteoporosis treatment in Europe since 2004. This article describes a large European observational survey of the use of strontium ranelate in clinical daily practice. A retrospective observational registry included 32,446 women consulting for postmenopausal osteoporosis in seven countries. Within the registry, 12,046 women were receiving strontium ranelate and were followed up over 3 years. The baseline characteristics of the follow-up cohort were similar to those of the whole registry cohort (age, 68.9 ± 10.3 years; body mass index, 25.6 ± 4.3 kg/m(2); lumbar spine T-score, -2.57 ± 0.85 SD; femoral neck T-score, -2.11 ± 0.86 SD). At baseline, 77 % of patients had at least one risk factor for osteoporosis, and 46 % had a previous history of osteoporotic fracture. Mean duration of follow-up was 32.0 ± 9.7 months, and treatment duration was 25.2 ± 13.7 months (24,956 patient-years of treatment). Persistence with strontium ranelate was 80 % at 1 year, 68 % at 2 years, and 64 % at 32 months; most patients (about 80 %) reported rarely omitting a dose. At least one emergent adverse event was reported in 2,674 (22 %) patients, most frequently gastrointestinal side effects. The crude incidence of venous thromboembolic events was 2.1/1,000 patient-years. No cases of hypersensitivity reactions, such as drug rash with eosinophilia and systemic symptoms (DRESS), Steven-Johnson syndrome, or toxic epidermal necrolysis, were reported. During follow-up, a fracture occurred in 890 patients (7 %); 429 of the fractures were nonvertebral fractures. Our observational survey over 32 months indicated good rates of adherence with strontium ranelate and confirmed its good safety profile in the management of postmenopausal osteoporosis.

Use of strontium ranelate for the treatment of osteoporosis in young patients: 4-year follow-up of a male patient

Use of strontium ranelate for the treatment of osteoporosis in young patients: 4-year follow-up of a male patient

Atypical Femoral Fractures during Prolonged Use of Bisphosphonates: Short-Term Responses to Strontium Ranelate and Teriparatide

Atypical femoral fractures have rarely been reported in women taking bisphosphonates, but this is still a controversial issue. Data are derived mainly from observation studies because a post hoc analysis from a randomized clinical trial did not find any such association. The aim of this study was to report three cases of what are considered atypical femoral fractures and their responses to the use of strontium ranelate and teriparatide. We studied three postmenopausal women with a diagnosis of osteoporosis who suffered fractures of the subtrochanteric region and femoral diaphysis with no major trauma while on long-term use of bisphosphonates. All the major features of atypical femoral fractures highlighted in the Task Force Report of the American Society for Bone and Mineral Research were present in the three cases. They had had unconsolidated fractures for approximately 1 yr before being referred to our center. After 3 months on strontium ranelate 2 g/d, serum osteocalcin and serum β-carboxyterminal telopeptide had increased in case 1 by 125 and 100%, respectively, and in case 2 by 50 and 22%, respectively, with total closure of the fracture. In case 3, after 1 month on teriparatide 20 μg/d, a radiographic closure of the fracture was achieved, and 3 months later serum osteocalcin and serum β-carboxyterminal telopeptide had increased by 300 and 22%, respectively. Our finding showed that both teriparatide and strontium ranelate had a rapid bone anabolic effect on unhealed atypical fractures associated with chronic bisphosphonate use.

STRONTIUM RANELATE IS THE DRUG OF CHOICE IN THE TREATMENT OF OSTEOPOROSIS

The paper gives the data of current studies, which suggest the dual mechanism of action of strontium ranelate on bone remodeling in postmenopausal osteoporosis (OP): the drug made bone rearrangement balance shift toward a predominance of the processes of new bone formation. Long-term studies dealing with the use of strontium ranelate to treat postmenopausal OP have supported its safety and efficacy. Strontium ranelate is stated to be the drug of choice in treating his pathology, the duration of the therapy may be as long as 8 years. Indications for its use may be further extended after clinical trials.

Treatment for osteoporosis in Australian residential aged care facilities: consensus recommendations for fracture prevention

Older people living in residential aged care facilities (RACFs) are at considerably higher risk of suffering fractures than older people living in the community. When admitted to RACFs, patients should be assessed for fracture risk to ensure early implementation of effective fracture prevention measures. Routine or regular determination of calcium and phosphate serum levels in institutionalised older people is not indicated. Opinion is divided about the value of routine measurements of serum concentrations of 25-hydroxyvitamin D, parathyroid hormone and bone turnover markers. The non-pharmacological approach to fracture prevention includes multifactorial programs of falls prevention and the use of hip protectors. Vitamin D supplementation is recommended for all patients in RACFs. Dietary calcium intake should be optimised (1200-1500 mg per day is recommended) and supplementation offered to those with inadequate intake. The decision to prescribe calcium supplements should be guided by patients' tolerance, whether or not they have a history of kidney stones, and emerging data about its cardiovascular safety. Bisphosphonates are the first-choice pharmacological agents for fracture prevention in older persons at high risk. Intravenous administration is as efficient as oral and has the significant advantage of better adherence. Use of strontium ranelate has not been tested on people in RACFs, but evidence in the "old-old" (those aged 75 years and older) suggests it could be a therapeutic option for fracture prevention in this setting. In general, teriparatide should not be considered as a first-line treatment for fracture prevention, particularly for people in RACFs.

Impacto de una alerta sanitaria sobre la utilización de ranelato de estroncio

Objective To evaluate changes in the use of strontium ranelate following a health safety warning in November 2007 on the risks of the development of DRESS (Drug Rash with Eosinophilia and Systemic Symptoms) with the use of this medicine. Method Monthly strontium ranelate DHD (daily defined doses/1,000 inhabitants/day) were calculated between 2006 and 2008 in a health area of Spain. The data were analyzed graphically and through a multiple regression model. Results Graphical representation showed a long-term rising trend throughout the study period, although growth slowed after the safety warning was issued. The multiple regression model showed that the health warning was statistically significant. Conclusion The use of strontium ranelate continues to grow after the issue of the health safety warning, although at a slower pace than previously.