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PubMed1995

Scanning electron microscopy and energy dispersive spectroscopy analysis of calciotraumatic lines in rat labial dentin after acute exposure to strontium chloride.

Rats were given strontium chloride (SrCl2) intraperitoneally at a dose of 500 mg/kg. The upper incisors were removed after injection of strontium. These incisors were studied by scanning electron microscopy-energy dispersive spectroscopy analysis (SEM-EDS) and light microscopy to examine the calciotraumatic lines of strontium in the rat incisor labial dentin. At 24 hours after injection of strontium, the calciotraumatic response was observed in the predentin using hematoxylin and eosin (H-E) staining. At 5 days, three layers of calciotraumatic lines were present in the labial dentin using an H-E staining and backscattered electron imaging in the SEM. The external layer consisted of unmineralized dentin, the intermediate layer of relatively unmineralized dentin, ane the internal layer of unmineralized dentin. By SEM-EDS analysis, strontium was detected in these layers. The elemental dot map showed that the external and internal unmineralized layers had a low calcium content. The magnesium concentration was higher in the internal unmineralized layer than the external unmineralized layer.

Animals↗
PubMed1993

[The oral strontium load test in the assessment of intestinal calcium absorption].

A close correlation between calcium and strontium intestinal absorption has been described. In this study, a test using Stable Strontium has been assessed in women without abnormal calcium or bone metabolism, with no history of drugs which might affect calcium or bone metabolism. Decreasing values of Strontium intestinal absorption, according to the length of the postmenopausal period, have been observed. Besides, the Stable Strontium Test has been given in postmenopausal women with osteoporotic femur fractures. In comparison with age matched healthy women, this latter group showed a significantly lower Strontium intestinal absorption. Analogous behaviour has been reported for Calcium intestinal absorption.

Administration, Oral↗
PubMed1964

STRONTIUM 90: ESTIMATION OF WORLDWIDE DEPOSITION.

The relation between the worldwide deposition of strontium-90, as calculated by many investigators over the last decade, and that observed in rainfall in New York City has been relatively constant. On the average, for each millicurie of strontium-90 per square mile deposited in New York City, 0.055 megacurie has been deposited on the earth's total surface. Cumulative deposits of strontium-90 on the earth's surface at various intervals over the last 10 years have been computed from this ratio. From the mean quarterly fraction of the annual strontium-90 fallout in New York City for the last 9 years, the worldwide deposition of this nuclide, equal to 2.48 megacuries, is predicted for 1964.

New York↗
PubMed2003

Design and methodology of the phase 3 trials for the clinical development of strontium ranelate in the treatment of women with postmenopausal osteoporosis.

The phase 3 program for strontium ranelate, a new oral agent in the treatment of women with postmenopausal osteoporosis, was aimed to assess the efficacy and safety of the daily oral dose of 2 g. This program was conducted in 12 countries, involved 75 centers, and was structured in 3 studies: FIRST (Fracture International Run-in for Strontium ranelate Trial), SOTI (Spinal Osteoporosis Therapeutic Intervention study) and TROPOS (TReatment Of Peripheral OSteoporosis). FIRST, a run-in open study, was designed to start the normalization of the calcium and vitamin D status of the patients, check all entry criteria, and ensure inclusion of a sufficient number of well-motivated patients in either one of the two therapeutic intervention protocols, SOTI or TROPOS: FIRST included 9,196 patients. SOTI and TROPOS were prospective, randomized, double-blind clinical trials comparing, in two parallel groups, the daily oral dose of 2 g of strontium ranelate with placebo, the patients of both groups receiving calcium and vitamin D according to their own deficiencies. The main objective of SOTI and TROPOS was to demonstrate a reduction in the incidence of postmenopausal women experiencing a new osteoporotic fracture (vertebral fracture in SOTI and nonvertebral fracture in TROPOS) over a 3-year treatment period, the total duration of the studies being 5 years. SOTI included 1,649 women with at least one osteoporotic vertebral fracture at inclusion and a lumbar BMD </=0.840 g/cm(2). TROPOS included 5,091 women with a femoral neck BMD </=0.600 g/cm(2). The phase 3 program for the clinical development of strontium ranelate in women with postmenopausal osteoporosis is a long-term program with the main statistical analysis after 3 years of treatment. Its aim is to demonstrate the effect of strontium ranelate on the axial and appendicular skeleton as well as its tolerability in osteoporotic patients with replete calcium and vitamin D stores.

Aged↗
PubMed2005

Clinical effects of strontium ranelate in women with postmenopausal osteoporosis.

Postmenopausal osteoporosis has long-term physical, psychological, and social consequences with a major impact on patients' daily life. Treatment for such a chronic disease needs to be clinically effective and well tolerated, and should ultimately result in a beneficial effect on quality of life. The antifracture efficacy of strontium ranelate, 2 g/day orally, an agent that appears to have dissociation effects on resorption and formation, has been assessed in two large, randomized, double-blind, placebo-controlled clinical studies: the Spinal Osteoporosis Therapeutic Intervention (SOTI) trial and the TReatment Of Peripheral Osteoporosis Study (TROPOS), including more than 6,700 postmenopausal women. Pending the results of TROPOS, a 3-year analysis of SOTI results shows that strontium ranelate significantly reduces new vertebral and clinical vertebral fracture incidence in postmenopausal osteoporotic women. This significant reduction in the risk of clinical and new vertebral fractures has been demonstrated as early as after 1 year of treatment (RR = 0.48, p = 0.003; and RR = 0.51, p < 0.001, respectively) and is maintained over 3 years (RR = 0.62, p < 0.001; and RR = 0.59, p < 0.001, respectively). This is accompanied by decreased back pain and body height loss in the strontium ranelate group compared with the placebo group. As strontium ranelate appears to improve clinical signs and is, furthermore, well tolerated especially in the upper gastrointestinal region, this treatment is expected to result in an improved health-related quality of life (HRQoL). Strontium ranelate thus offers significant clinical benefits in terms of efficacy, tolerability, and ease of administration in the treatment of postmenopausal women with vertebral osteoporotic fractures.

Aged↗
PubMed2005

Strontium ranelate: a novel mode of action leading to renewed bone quality.

Various bone resorption inhibitors and bone stimulators have been shown to decrease the risk of osteoporotic fractures. However, there is still a need for agents promoting bone formation by inducing positive uncoupling between bone formation and bone resorption. In vitro studies have suggested that strontium ranelate enhances osteoblast cell replication and activity. Simultaneously, strontium ranelate dose-dependently inhibits osteoclast activity. In vivo studies indicate that strontium ranelate stimulates bone formation and inhibits bone resorption and prevents bone loss and/or promotes bone gain. This positive uncoupling between bone formation and bone resorption results in bone gain and improvement in bone geometry and microarchitecture, without affecting the intrinsic bone tissue quality. Thus, all the determinants of bone strength are positively influenced. In conclusion, strontium ranelate, a new treatment of postmenopausal osteoporosis, acts through an innovative mode of action, both stimulating bone formation and inhibiting bone resorption, resulting in the rebalancing of bone turnover in favor of bone formation. Strontium ranelate increases bone mass while preserving the bone mineralization process, resulting in improvement in bone strength and bone quality.

Bone Density↗
PubMed2006

An economic evaluation of strontium ranelate in the treatment of osteoporosis in a Swedish setting: based on the results of the SOTI and TROPOS trials.

INTRODUCTION: Strontium ranelate is a new therapy for the treatment and prevention of osteoporosis that has been shown in two phase III clinical trials (the Spinal Osteoporosis Therapeutic Intervention [SOTI] and the Treatment Of Peripheral OSteoporosis Study [TROPOS] trials) to reduce the risk of osteoporotic fractures at the vertebral, non-vertebral and hip level in postmenopausal women. The aim of this study was to estimate the potential cost-effectiveness of strontium ranelate in the treatment of osteoporosis in postmenopausal Swedish patients. METHODS: A Markov cohort model was adapted to fit patients corresponding to the patients in the SOTI and TROPOS clinical trials. The model was populated with Swedish cost and epidemiological data. In the base case, the cost-effectiveness was estimated for 69-year old women with low bone mineral density (BMD) and prevalent vertebral fractures (SOTI) and for 77-year old women with low BMD (TROPOS). The cost-effectiveness analysis had a societal perspective. RESULTS: In the base case analysis, the cost per quality-adjusted life years (QALY) gained of strontium ranelate patients compared to no treatment patients was estimated at SEK 472,586 and SEK 259,643, including costs in added life years, based on the SOTI and the TROPOS trials, respectively. Excluding cost in added life years, the cost per QALY gained was estimated at SEK 336,420 (SOTI) and SEK 165,680 (TROPOS). In subgroup analyses, in patients 74 years and older with a T-score lower than -2.4 and patients older than 80 years of age, strontium ranelate was found to be cost saving compared to no treatment. CONCLUSIONS: The results in the base case analyses and the sensitivity analyses of this study indicate that, compared to no treatment, strontium ranelate is cost-effective in the treatment of postmenopausal women with low BMD.

Aged↗
PubMed2006

Strontium ranelate: vertebral and non-vertebral fracture risk reduction.

Fractures are common at the spine and hip, but at least half the morbidity and mortality of fractures in the community come from fractures that involve other sites. Over half of all fractures arise in individuals without osteoporosis, whereas the highest risk group for fractures are individuals over 80 years of age. Reducing the burden of fractures should thus include an assessment of drug efficacy against all fractures in a wide range of individuals. For vertebral fractures, in the phase III Spinal Osteoporosis Therapeutic Intervention study of 1649 postmenopausal women with osteoporosis, 2 g strontium ranelate a day produced a risk reduction of 49% in the first year and 41% during 3 years. In the TReatment Of Peripheral OSteoporosis study, which was designed to examine the effect of strontium ranelate on non-vertebral fractures, of the 5091 patients, 3640 had spine X-rays. The vertebral fracture risk reduction was 45% at one year and 39% over 3 years. In a preplanned pooling of the above two studies, 1170 patients had vertebral osteopenia. Strontium ranelate reduced the risk of vertebral fracture in 3 years by 40% in these patients. In 409 patients with lumbar or femoral neck osteopenia, strontium ranelate reduced the risk of vertebral fractures by 62% over 3 years. In the pre-planned pooling of data from the two studies, in 1488 women aged between 80 and 100 years (mean age 84 +/- 3 years), the risk of 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, treatment for 3 years reduced the fracture risk by 16%, and by 19% for major fragility fractures. In a post-hoc analysis of 1977 women at high risk of hip fracture (aged > or = 74 years and with a femoral neck bone mineral density T-score < or = -2.4) the hip fracture risk was reduced by 36%. In patients aged 80 and over in the pre-planned pooling of data from the two studies, the risk of an incident non-vertebral fracture was reduced by 41% in the first year and by 31% over 3 years. Strontium ranelate, a new anti-osteoporosis agent, has a broad range of antifracture efficacy.

Aged↗
PubMed2005

A new treatment for post-menopausal osteoporosis: strontium ranelate.

Strontium ranelate is a new anti-osteoporotic agent which appears to reduce bone resorption by decreasing osteoclast differentiation and activity, and to stimulate bone formation by increasing replication of pre-osteoblast cells, leading to increased matrix synthesis. This review examines both the scientific rationale for its use in post-menopausal osteoporosis and the evidence of its antifracture efficacy. In the placebo-controlled, phase III trial Spinal Osteoporosis Therapeutic Intervention (SOTI) (no.=1442; mean age 69 yr), there was a 41% decrease over 3 yr in the number of patients with new vertebral fracture in the strontium ranelate (2 g/day) group vs placebo (p<0.001), and a 14.4% difference in lumbar bone mineral density (BMD) at 3 yr vs placebo. This reduction in vertebral fracture risk was already detected after 12 months (49% lower risk, p<0.001). The phase III TReatment Of Peripheral OSteoporosis (TROPOS) study assessed the efficacy of strontium ranelate (2 g/day) in preventing non-vertebral fracture in post-menopausal osteoporosis (no.=4932; mean age 77 yr). Strontium ranelate reduced non-vertebral fracture risk by 16% vs placebo (p=0.04) and hip fracture risk by 36% (p=0.031), in osteoporotic patients older than 74 yr. There was a concomitant increase in BMD throughout the study, reaching +8.2% (femoral neck) and +9.8% (total hip) at 3 yr. Strontium ranelate is thus a first-choice treatment of post-menopausal osteoporosis as it significantly reduces vertebral, non-vertebral and hip fracture risk in post-menopausal osteoporotic women, as well as having an excellent tolerability profile.

Bone and Bones↗
PubMed1957

Strontium-calcium movement from soil to man.

The calcium reservoirs of the biosphere are becoming labeled to varying degrees with strontium-90 from nuclear weapons. These reservoirs include the human and animal skeleton, the milk, the vegetation, the upper layers of soil, and the waters. The degree of labeling is governed by the dilution that occurs, or the differential behavior of calcium and strontium in various steps of the food chain. This differential behavior normally provides a factor of protection against strontium-90 in the soil and vegetation that may be as high as 25 for the newborn and is most likely not less than 6 for adults, depending on food habits. The physiological steps that are important in the movement of the two elements in the biosphere are described to provide a basis for an approach toward increase of the discrimination against strontium in favor of calcium. Some aspects of agricultural practices are discussed from this standpoint. The matter of hazard from levels now existing and the present need to undertake remedial measures are not discussed, in major part because of lack of experimental data on which to base such considerations.

Adult↗
PubMed1991

Strontium-89 chloride for pain palliation in prostatic skeletal malignancy.

In a multi-centre study strontium-89 was shown to be effective in relieving bone pain from prostatic carcinoma in patients who had failed conventional therapies. Of 83 patients assessed at 3 months, following the administration of a dose of at least 1.5 MBq/kg, 75% derived benefit and 22% became pain free. Symptomatic improvement usually occurred within 6 weeks and continued for between 4 and 15 months (mean 6 months). Based on the dose estimation part of this study the recommended dose of strontium-89 is 150 MBq. Toxicity was low, provided platelet levels were above 100 x 10(9) l-1 at the time of treatment. Repeat treatments with strontium-89 may be given at intervals of not less than 3 months. Strontium-89 is administered intravenously on an out-patient basis with no special radiological protection precautions.

Bone Neoplasms↗
PubMed1976

[Effects of different metabolites of vitamin D3 and of calcium concentration on the intestinal absorption of strontium].

The effect of calcium concentration and vitamin B3 25 OHD3 and 1.25 diOHD3 upon intestinal strontium transport was studied in vitamin D deficient rats with duodenal perfusion in situ. When the calcium concentration was increased, the strontium passive absorption was decreased. The vitamin D3 and its derivatives increased intestinal strontium transport significantly and this increment was not modified by calcium. In our experiment, calcium is competitive with strontium only in passive absorption.

Animals↗
PubMed1996

Pain palliation with strontium-89 in children with metastatic disease.

We report two cases of children with metastatic bone disease who received strontium-89 intravenously. An 11-year-old boy with stage IV neuroblastoma received 50 microCi/kg of strontium-89. He had a good response, and his pain abated to the point that he could be taken off IV Dilaudid and was discharged from the hospital. A 7-year-old girl with the diagnosis of squamous cell carcinoma of the lung disclosed minimal increased uptake on a bone scan. Following the strontium-89 therapy, she did not have any significant improvement in pain, probably due to the minimal osteoblastic activity evidenced by the minimal abnormalities on the bone scan. Until this report there has been no reported case of using strontium-89 in the treatment of children with metastatic disease.

Analgesics, Opioid↗
PubMed2002

A multiinstitutional, concurrent chemoradiation trial of strontium-89, estramustine, and vinblastine for hormone refractory prostate carcinoma involving bone.

BACKGROUND: Estramustine phosphate (EMP) and vinblastine have radiosensitizing properties and significant activity against hormone refractory prostate carcinoma. Strontium-89 is a palliative agent that acts as a selective radiation source for bone metastasis. The combination of EMP, vinblastine, and strontium-89 was developed to exploit the potential for radiosynergy. PATIENTS AND METHODS Forty-four patients at the Brown Oncology Group affiliated hospitals were treated with oral EMP 600 mg/m2 daily on Weeks 1-4 and 7-10, vinblastine 4 mg/m2 intravenously once each week on Weeks 1-4 and 7-10, and strontium-89 2.2 MBq/kg on Day 1. Courses were repeated every 12 weeks. Response assessment was based on a change in the serum prostate specific antigen (PSA) levels, correlated with change in measurable disease and bone scan appearance. RESULTS: A greater than or equal to 50% decline in PSA for at least 6 weeks was observed in 21 patients (48%, 95% confidence interval, 33-62%). Median duration of response was 23 weeks (range, 6-70.8 weeks). The median survival was 13 months with 1- and 2-year survival rates of 55% and 25%, respectively. After completion of protocol therapy, a retrospective review showed that only nine patients received subsequent palliative external beam radiation after progression. CONCLUSIONS: The addition of strontium-89 to the regimen of EMP and vinblastine can be delivered safely and in repeated doses, provides effective palliation, and may decrease the need for future radiation therapy. A randomized trial is necessary to quantify these effects.

Administration, Oral↗
PubMed1989

Zinc and strontium analyses by energy dispersive X-ray fluorescence in human permanent teeth.

The zinc and strontium content of enamel and dentine from humans aged 9-64 yr was analysed, after systematic sampling, by X-ray fluorescence. Relatively high levels of zinc were found in both hard tissues but there was no significant increase with age. Zinc content decreased significantly from outer to inner enamel and increased significantly again from peripheral to pulpal coronal and root dentine. The strontium content was significantly higher in enamel than in dentine; there was a significant increase with age in enamel but not in dentine. However, outer and inner enamel showed no significant difference in strontium content. Almost similar amounts of strontium were found in coronal and root dentine.

Adolescent↗
PubMed1995

Changes in the plasma electrolytes and metabolites of the rat following acute exposure to sodium fluoride and strontium chloride.

Acute exposure of rats to strontium or fluoride by i.p. injection of sodium fluoride or strontium chloride resulted in a systemic response in which changes occurred in the plasma electrolytes and metabolites. Strontium resulted in a rapid but temporary hypercalcaemia while fluoride produced a temporary hypocalcaemia. There was no significant hypophosphataemia after fluoride and only a transient hypophosphataemia with strontium. There was some indication of kidney damage and a general stress response following fluoride injection. These results do not support the hypothesis that interglobular dentine is associated with hypophosphataemia or hypoplastic enamel with hypocalcaemia and are in conflict with the observation that the formation of interglobular dentine following the injection of lead acetate is associated with hyperphosphataemia and hypercalcaemia.

Amelogenesis↗
PubMed1989

The effect of strontium on the drug-receptor interaction on cholinergic drugs.

The effect of replacing calcium with strontium in the perfusion fluid was qualitatively and quantitatively studied in the isolated longitudinal muscle of the guinea-pig ileum. In the presence of strontium hyoscine could be considered a competitive antagonist of acetylcholine for the acetylcholine receptor of the longitudinal muscle of the guinea-pig ileum; dibenamine still blocked this receptor in an irreversible way. The equilibrium constants for acetylcholine (KA) and hyoscine (KI) were obtained in the presence of calcium (KA = 3.16 +/- 0.63 microM; KI = 0.38 +/- 0.07 nM), and strontium (KA = 7.00 +/- 0.89 microM; KI = 0.93 +/- 0.16 nM). The results show a decrease in the affinity of both drugs for the muscarinic receptor in the presence of strontium.

Acetylcholine↗
PubMed2005

Effect of strontium ions on the growth of ROS17/2.8 cells on porous calcium polyphosphate scaffolds.

Preparation, characterization and cellular biocompatibility study of a series of calcium polyphosphate containing 0-100 mol% of Ca2+ replaced by Sr2+ were reported. The osteoblastic ROS17/2.8 cell line was used and seeded on the strontium-doped calcium polyphosphate (SCPP) scaffolds to estimate its optimal dose and to study its potential to support the growth of osteoblastic cells for bone tissue engineering. The effects of SCPP on cells' proliferation and differentiation were evaluated by MTT and ALP activity assay. The results showed that porous SCPP did not exert cytotoxic effect on the cells. In addition, the proliferation and differentiation of the growth of ROS17/2.8 cells on the SCPP containing a low dose of strontium showed a higher level compared to the control, and the SCPP containing 1% strontium was optimal according to the results of MTT and ALP activity assay. The cells on the porous SCPP formed a continuous layer on the outer and inner surface observed by scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM). The bunchy collagens were excreted from the cells and the calcium granules wrapped by collagens were sedimentated on the surface of cells. The results suggested that the biodegradable SCPP could stimulate the proliferation and differentiation of ROS17/2.8 cells in vitro after addition of proper dose of strontium. The porous SCPP may be a promising material for the bone tissue engineering.

Alkaline Phosphatase↗