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Strontium concentrations in whole human saliva.

Whole unstimulated saliva samples were collected from 91 male, 14-yr-old school children in seven Wisconsin (U.S.A.) communities with varying strontium levels in their drinking water (0.22-33.6 mg/l). There was a mean concentration of 0.035 mg/l (+/- 0.001 SEM) with a range of 0.02 to 2.93 mg/l of strontium. Saliva-strontium concentrations were weakly associated with drinking-water concentrations. A negative relationship between saliva-strontium concentrations and caries prevalence was found. Strontium concentrations in saliva were related to time of ingestion of the element and levels of strontium as high as 15 mg/l occurred in saliva within 1 hr of ingesting 30 mg strontium as a single dose.

Adolescent↗

Use of strontium in the activation of bovine oocytes reconstructed by somatic cell nuclear transfer.

As an important step in the nuclear transfer (NT) procedure, we evaluated the effect of three different treatments for oocyte activation on the in vitro and in vivo developmental capacity of bovine reconstructed embryos: (1) strontium, which has been successfully used in mice but not yet tested in cattle; (2) ionomycin and 6-dimethylaminopurine (6-DMAP), a standard treatment used in cattle; (3) ionomycin and strontium, in place of 6-DMAP. As regards NT blastocyst development, no difference was observed when strontium (20.1%) or ionomycin/6-DMAP (14.4%) were used. However, when 6-DMAP was substituted by strontium (3), the blastocyst rate (34.8%) was superior to that in the other activation groups (p < 0.05). Results of in vivo development showed the possibility of pregnancies when NT embryos activated in strontium were transferred to recipient cows (16.6%). A live female calf was obtained when ionomycin/strontium were used, but it died 30 days after birth. Our findings show that strontium can be used as an activation agent in bovine cloning procedures and that activation with a combination of strontium and ionomycin increased the in vitro developmental capacity of reconstructed embryos. This is the first report of a calf produced by adult somatic cell NT in Latin America.

Adenine↗

Recycling of synaptic vesicles at the frog neuromuscular junction in the presence of strontium.

In these experiments, we followed the exocytosis and endocytosis of synaptic vesicles with the vital dye FM1-43 and asked whether calcium is important for membrane retrieval at the frog neuromuscular junction. We replaced calcium with equimolar amounts of strontium and monitored the staining of recycling vesicles by inducing exocytosis with electrical stimulation. Trains of 2,400 (2 or 20 Hz) or 4,200 (20 Hz) pulses failed to induce FM1-43 internalization in the presence of strontium, but they did in the presence of calcium. This effect of strontium was not due to a decrease in exocytosis, because FM1-43 release was similar in the presence of calcium or strontium. The impairment in endocytosis, observed as inhibition of FM1-43 internalization, could be overcome by longer periods of stimulation (6,000 pulses at 2 or 20 Hz) in the presence of strontium (1.8 mM) or by increasing the extracellular concentration of strontium to 10 mM (2,400 action potentials at 20 Hz). It is suggested that endocytosis is dependent on calcium influx and that strontium is much less effective in replacing calcium for endocytosis than it is for exocytosis.

Action Potentials↗

Predictors of response to strontium-89 (Metastron) in skeletal metastases from prostate cancer: report of a single centre's 10-year experience.

An analysis of prospectively collected data from 75 patients with bone metastases secondary to prostate cancer who were treated with strontium-89 injection in a single centre over a 10-year period, is presented. The surrogate role of markers of disease progression (haemoglobin and prostate specific (PSA) antigen levels; number of bone scan-positive sites), symptomatic factors (analgesic intake; number of painful bone sites) and history of prior external radiotherapy, were analysed to determine whether any parameters had a predictive effect on the success of strontium-89 treatment. The success of strontium-89 injection was determined by calculating the change in number of sites of bone pain (pain sites) and analgesic intake. The outcome was classed as successful in 42 (56.0%) patients, unsuccessful in 13 (17.3%) and unchanged in 20 (26.7%). Proportionately more of the patients who had 'superscans' on bone scintigraphy at baseline had an unsuccessful outcome after a strontium-89 injection (5/7; 71.4%); for those with fewer bone scan-positive sites the majority had successful outcomes. Patients with a successful outcome had a significantly better survival rate after strontium-89 injection. Multivariate analysis showed haemoglobin level, PSA level and outcome after strontium-89 treatment to be significant independent prognostic variables; no change/unsuccessful outcome, a high PSA level prior to treatment, and a low haemoglobin level were associated with poor survival. It is suggested that early treatment with strontium-89 (Metastron) in patients with fewer bone metastases is more likely to be successful, with a longer time before further therapy required.

Aged↗

Evaluation of potential strontium chelators in an octanol-water system.

90Sr has a physical half-life of sufficient duration to make it a potentially dangerous contaminant from nuclear accidents and radioactive wastes. In the present study, the efficacy of 16 compounds as potential chelators of strontium was tested in vitro. Strontium solubilization from strontium carbonate and its distribution in an octanol-water system (Do/w) was determined in the absence and presence of alpha-ketoglutaric acid, Kryptofix 222, ethylenglycol-bis-(beta-amino-ethylether)-N,N-tetraacetic acid, diethylentriamine pentaacetic acid, Kryptofix 5, disodium chlodronate, disodium ethidronate, oxaloacetic acid, fumaric acid, D-gluconic acid, succinic acid, citric acid, D,L-2,3-diaminopropionic acid, 1,1-cyclohexanediacetic acid, tartaric acid, and trans-1,2-cy-clohexanediol. Kryptofix 222 and Kryptofix 5 significantly increased solubilized strontium, suggesting strontium chelation potential. Since in previous in vivo studies both compounds were also effective in the removal of strontium following internal contamination, it is concluded that the octanol-water system may be useful screening compounds with strontium chelation potential.

Bridged Bicyclo Compounds↗

Solubility of various forms of strontium titanate in lungs: in vitro and in vivo studies.

At the In-Tank Precipitation Facility of the Savannah River Site, strontium and other radionuclides are removed from high-level radioactive waste and sent to the Defense Waste Processing Facility. Strontium removal is accomplished by adsorption using a slurry that includes monosodium titanate, which forms strontium titanate with unknown lung solubility characteristics. The purpose of this study was to determine the solubility of strontium titanate in the form created at the In-Tank Precipitation facility. An in vitro dissolution study was done with a slurry simulant and with several types of strontium titanate, and the results were compared. An in vivo study was also performed with high-fired SrTiO3 in rats. Strontium and titanium were measured by inductively-coupled plasma/atomic emission spectrometry. The data from both studies were used independently to assign the compounds to an absorption type based on criteria specified in ICRP 71. Results of the in vitro studies showed that the Defense Waste Processing Facility simulant should be assigned to Type M and the strontium titanate should be assigned to Type S. Results of the in vivo study verified that SrTiO3 should be assigned to Type S. Lung clearance data of SrTiO3 from rats showed that 85% cleared within the first 24 h and the remaining 15% cleared with a half-time of 130 d. The initial rapid clearance is attributed to deposition in airways as compared to the alveolar region.

Animals↗

Vertebroplasty by use of a strontium-containing bioactive bone cement.

STUDY DESIGN: A review of the laboratory and clinical data for a new strontium-containing hydroxyapatite bioactive bone cement. OBJECTIVES: To compare the properties of the strontium-containing bioactive bone cement with those of polymethyl methacrylate (PMMA) and hydroxyapatite (HA) bone cements. SUMMARY OF BACKGROUND DATA: Vertebroplasty and kyphoplasty using conventional PMMA bone cements have been effectively used to treat osteoporotic spine fractures with good short- and medium-term results. However, PMMA has some undesirable properties, including its high setting temperature, lack of osseointegration, and large stiffness mismatch with osteoporotic bone. These properties are responsible for some postoperative complications. METHODS: Strontium-containing hydroxyapatite (Sr-HA) bioactive bone cement consists of a filler blend of strontium-containing hydroxyapatite, fumed silica and benzoyl peroxide; and a resin blend of bisphenol A diglycidylether methacrylate, triethylene glycol dimethacrylate, poly(ethylene glycol) methacrylate, and N, N-dimethyl-p-toluidine. Its properties, including mechanical strength, setting temperature, biocompatibility, and osseoinduction, were compared with other cements in vitro and in vivo. Early clinical results are presented. RESULTS: The Sr-HA cement has a setting time of 15 to 18 minutes, a maximum setting temperature of 58 degrees C, a compressive strength of 40.9 MPa, bending strength of 31.3 MPa, and a bending modulus of 1,408 MPa. The bending strength and modulus are closer to human cancellous bone. Sr-HA cement promotes osteoblast attachment and mineralization in vitro and bone growth and osseointegration in vivo. In a pilot study, 23 cases of osteoporotic fractures treated with this cement with a mean follow-up of 18 months suggest that it is as effective as PMMA in relieving pain. DISCUSSIONS: Oral strontium has been shown to induce new bone formation and is effective in reducing fracture risk in osteoporosis. Our data suggest that strontium delivered locally has the same effect; thus, the combination of strontium with HA in a cement with a low setting temperature, adequate stiffness, and low viscosity makes this a good bioactive cement for vertebroplasty and kyphoplasty.

Animals↗

Processes modulating calcium distribution in citrus leaves. An investigation using x-ray microanalysis with strontium as a tracer.

Citrus leaves accumulate large amounts of calcium that must be compartmented effectively to prevent stomatal closure by extracellular Ca2+ and interference with Ca(2+)-based cell signaling pathways. Using x-ray microanalysis, the distribution of calcium between vacuoles in different cell types of leaves of rough lemon (Citrus jambhiri Lush.) was investigated. Calcium was accumulated principally in palisade, spongy mesophyll, and crystal-containing idioblast cells. It was low in epidermal and bundle sheath cells. Potassium showed the reverse distribution. Rubidium and strontium were used as tracers to examine the pathways by which potassium and calcium reached these cells. Comparisons of strontium and calcium distribution indicated that strontium is a good tracer for calcium, but rubidium did not mirror the potassium distribution pattern. The amount of strontium accumulated was highest in palisade cells, lowest in bundle sheath and epidermal cells, and intermediate in the spongy mesophyll. Accumulation of strontium in palisade and spongy mesophyll was accompanied by loss of potassium from these cells and its accumulation in the bundle sheath. Strontium moved apoplastically from the xylem to all cell types, and manipulation of water loss from the adaxial leaf surface suggested that diffusion is responsible for strontium movement to this side of the leaf. The results highlight the importance of palisade and spongy mesophyll as repositories for calcium and suggest that calcium distribution between different cell types is the result of differential rates of uptake. This tracer technique can provide important information about the ion uptake and accumulation properties of cells in intact leaves.

Biological Transport↗

Intravenous strontium gluconate as a kinetic marker for calcium in healthy volunteers.

1. We have studied the pharmacokinetics of stable strontium in 10 healthy male volunteers. We gave each volunteer 5 mmol strontium gluconate by intravenous infusion over 1 h and measured strontium concentrations in plasma and urine samples for 20 days. The plasma strontium concentration vs time data for each volunteer were fitted by a triexponential function using NONLIN. Compartmental model-dependent and model-independent pharmacokinetic variables were then calculated. 2. The mean half-life we report (5.4 days) is longer than that previously reported (about 2 days), since we continued sampling for 20 days. However, the rates of clearance (CL 9.4 ml min-1. CLR 5.4 ml min-1, and CLNR 4.0 ml min-1) are similar to those previously reported, and the apparent volume of distribution at steady state (64 l) is similar to the values previously reported for the size of the exchangeable pool of both strontium and calcium. 3. The similarities in the pharmacokinetic behavior of strontium and calcium suggest that the in vivo disposition of strontium may be used as a marker of calcium disposition and for studying the effects of drugs such as the calcium antagonists.

Adult↗

EDTA enhancement of strontium uptake by intact human enamel.

The aim of this research was to study the effect of EDTA on the strontium uptake by intact tooth enamel. EDTA did not significantly affect the strontium uptake in an acid medium of pH 4.5. However, it caused a sharp rise in strontium uptake at pH 6.0. At such a pH, the stability constants of the Ca-EDTA complex are approaching a maximal value, and as a result of it a significant dissolution of the surface enamel, accompanied by a highly effective increase of the contact area for strontium uptake, is taking place. In all the experiments, treatment with strontium solution resulted in a decrease of the solubility and dissolution rate of enamel in an acidic environment. The resistance of enamel to acid attack was proportional to the quantity of absorbed strontium, reaching maximal values after treatment with strontium solutions in 10(-2) M EDTA at pH 6.0.

Dental Enamel↗

Quantification of bone strontium levels in humans by in vivo x-ray fluorescence.

The need for in vivo bone strontium assessment arises because strontium may exert a number of effects on bone, which may be either beneficial or toxic. Measurements discussed here are noninvasive, no sample is taken, nor is there discomfort to patients. The developed source excited x-ray fluorescence system employs a 109Cd source to excite the strontium K x rays, with the source and detector in approximately 90 degree geometry relative to the sample position. The factors affecting the accuracy and minimal detectable limit for bone strontium in vivo measurements are discussed. A system calibration revealed a minimum detectible limit of approximately 0.25 mg Sr/g Ca, which is sufficient for the monitoring of strontium levels in healthy subjects and patients with elevated bone strontium concentrations. Preliminary in vivo measurements in ten healthy subjects at two bone sites (phalanx and tibia) indicated that this system can be applied for cumulative bone strontium estimation while delivering a low effective dose of 80 nSv during the measurement time. Future work will involve attempts to enhance system precision with alternative fluorescing sources and further optimization of the detection system.

Bone and Bones↗

Endotrophic calcium, strontium, and barium spores of Bacillus megaterium and Bacillus cereus.

Foerster, Harold F. (The University of Texas, Austin), and J. W. Foster. Endotrophic calcium, strontium, and barium spores of Bacillus megaterium and Bacillus cereus. J. Bacteriol. 91:1333-1345. 1966.-Spores were produced by washed vegetative cells suspended in deionized water supplemented with CaCl(2), SrCl(2), or BaCl(2). Normal, refractile spores were produced in each case; a portion of the barium spores lost refractility and darkened. Thin-section electron micrographs revealed no apparent anatomical differences among the three types of spores. Analyses revealed that the different spore types were enriched specifically in the metal to which they were exposed during sporogenesis. The calcium content of the strontium and the barium spores was very small. From binary equimolar mixtures of the metal salts, endotrophic spores accumulated both metals to nearly the same extent. Viability of the barium spores was considerably less than that of the other two types. Strontium and barium spores were heat-resistant; however, calcium was essential for maximal heat resistance. Significant differences existed in the rates of germination; calcium spores germinated fastest, strontium spores were slower, and barium spores were slowest. Calcium-barium and calcium-strontium spores germinated readily. Endotrophic calcium and strontium spores germinated without the prior heat activation essential for growth spores. Chemical germination of the different metal-type spores with n-dodecylamine took place at the same relative rates as physiological germination. Heat-induced release of dipicolinic acid occurred much faster with barium and strontium spores than with calcium spores. The washed "coat fraction" from disrupted spores contained little of the spore calcium but most of the spore barium. The metal in this fraction was released by dilute acid. The demineralized coats reabsorbed calcium and barium at neutral pH.

Acids↗

Simple test of intestinal calcium absorption measured by stable strontium.

A clinical test of intestinal calcium absorption has been developed using non-radioactive stable strontium as a calcium tracer. In nine elderly subjects there was a close correlation between the fractional absorption of strontium and radioactive calcium (45Ca) during a five hour period after the simultaneous oral administration of the two tracers. Comparable precision was achieved with each tracer in six subjects in whom the test was repeated after two weeks. The effect of food on strontium absorption was examined in a further 33 normal subjects (age 21-60 years), and the administration of the strontium with a standard breakfast was shown to reduce the variance at individual time points. A simplified test in which serum strontium concentration was measured four hours after the oral dose given with a standard breakfast was adopted as the routine procedure. The normal range (mean (2 SD], established over 97 tests in 53 patients, was 7.0-18.0% of the dose in the extracellular fluid. A further 30 patients with possible disorders of calcium absorption (10 with primary hyperparathyroidism and 20 with coeliac disease) were studied by this standard test. In both groups of patients the mean four hour strontium values were significantly different from normal. This standard strontium absorption test allows assessment of calcium absorption with sufficient sensitivity and precision to have a wide application in clinical practice.

Adult↗

Preclinical screening of the applicability of strontium as a marker for intestinal calcium absorption.

The applicability of stable strontium as a marker for measuring intestinal calcium absorption is mainly dependent on the validity of the assumption that calcium and strontium are absorbed with a constant ratio. Up to now, it is not clear whether this ratio is affected by intervention therapy. Therefore, preclinical screening of this ratio before and after treatment is indispensable for a clinical calcium absorption test based on the use of stable strontium as a marker. We studied the effects of 1,25-dihydroxyvitamin D3 [1,25(OH)2D(3)], a potent enhancer of active intestinal calcium absorption, on the pharmacokinetics of both calcium-45 and strontium in adult male rats, in a short-term dose-finding study [0-50 ng 1,25(OH)2D(3)/100 g body weight] and also in a placebo-controlled study in which 12.5 ng 1,25(OH)2D(3)/100 g body weight were applied to assess the long-term pharmacokinetics. The mean bioavailability (true absorption) was 33% for calcium and 19% for strontium (ratio 1.7:1), whereas, after 1,25(OH)2D(3) pretreatment, it was 73 and 43% (ratio 1.7:1), respectively. These findings demonstrate that intestinal strontium absorption has, like intestinal calcium absorption, an active component. Moreover, they underscore the applicability of stable strontium as a tool for investigating calcium absorption under various conditions.

Animals↗

Effect of low doses of stable strontium on bone metabolism in rats.

The effects of low doses of oral stable strontium (0.19-0.40% of strontium chloride) on mineral and bone metabolism were examined in normal rats using biochemical and histomorphometrical methods. The strontium levels in serum and bone rose according to the intake of the element. Oral strontium supplementation did not produce deleterious effects on body growth or on mineral homeostasis except a transitory slight decrease in serum calcium. At the dosage level of 0.40% however, strontium induced a slight defective bone mineralization. At lower levels, treated rats showed stimulated bone formation evidenced by increased amount of osteoid and increased extent of tetracycline double-labelled surface while the mineralization lag time remained normal. The osteoclastic surface and the number of acid phosphatase-stained chondroclasts and osteoclasts remained unchanged. Stimulation of bone formation without apparent change in bone resorption resulted in a 10% increase in the trabecular calcified bone volume. The strontium-induced increased osteogenesis was not associated with changes in circulating levels of 1,25(OH)2 vitamin D or in parathyroid hormone effects. The results show that small doses of oral strontium may stimulate bone formation without altering bone resorption in the rat.

Animals↗

Local Structure Analysis of Strontium Sorption to Hydrous Manganese Oxide.

To develop mechanistic models of contaminant distribution processes, we conducted an X-ray absorption fine structure analysis of strontium sorption to hydrous manganese oxide (HMO). Sr K-edge measurements were performed at 298, 220, and 77 K, and at sample loadings from 10(-4) to 10(-2) mol Sr/g HMO. Results from fitting the first shell in the sorbed samples indicate that strontium is surrounded by 10-12 oxygen atoms at an average distance of 2.58 Å. This coordination environment is consistent with the strontium atom remaining hydrated upon sorption to the oxide, where in water hydrated strontium has approximately 9 atoms of oxygen at 2.62 Å. Furthermore, the temperature dependence of the strontium-oxygen bond also suggests physical adsorption due to the large contribution of the dynamic component of the Debye Waller factor. Although second-shell data are consistent with either 3 manganese atoms at 4.12 Å or 6 strontium atoms at 3.88 Å, both the near-edge and fine structure data for the manganese K-edge indicate that the local coordination environment of the manganese ion remains intact as a function of time or strontium sorption. Furthermore, the local structure of amorphous manganese oxide is highly ordered. Copyright 2000 Academic Press.

Journal Article↗

Strontium ranelate reduces the risk of nonvertebral fractures in postmenopausal women with osteoporosis: Treatment of Peripheral Osteoporosis (TROPOS) study.

BACKGROUND: Strontium ranelate, a new oral drug shown to reduce vertebral fracture risk in postmenopausal women with osteoporosis, was studied in the Treatment of Peripheral Osteoporosis (TROPOS) study to assess its efficacy and safety in preventing nonvertebral fractures also. METHODS: Strontium ranelate (2 g/d) or placebo were randomly allocated to 5091 postmenopausal women with osteoporosis in a double-blind placebo-controlled 5-yr study with a main statistical analysis over 3 yr of treatment. FINDINGS: In the entire sample, relative risk (RR) was reduced by 16% for all nonvertebral fractures (P = 0.04), and by 19% for major fragility fractures (hip, wrist, pelvis and sacrum, ribs and sternum, clavicle, humerus) (P = 0.031) in strontium ranelate-treated patients in comparison with the placebo group. Among women at high risk of hip fracture (age > or = 74 yr and femoral neck bone mineral density T score < or = -3, corresponding to -2.4 according to NHANES reference) (n = 1977), the RR reduction for hip fracture was 36% (P = 0.046). RR of vertebral fractures was reduced by 39% (P < 0.001) in the 3640 patients with spinal x-rays and by 45% in the subgroup without prevalent vertebral fracture. Strontium ranelate increased bone mineral density throughout the study, reaching at 3 yr (P < 0.001): +8.2% (femoral neck) and +9.8% (total hip). Incidence of adverse events (AEs) was similar in both groups. CONCLUSION: 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, and is well tolerated. It confirms that strontium ranelate reduces vertebral fractures. Strontium ranelate offers a safe and effective means of reducing the risk of fracture associated with osteoporosis.

Aged↗

The removal of strontium from the mouse by chelating agents.

The effects of the chelating agents monosodium glutamate, Tiron, tartaric acid, ascorbic acid, 1,4,7,10,13,16-hexaoxacyclooctadecane (18-crown-6), 2,3-dimercaptosuccinic acid (DMSA), succinic acid, malic acid, ethylendiaminetetraacetic acid (EDTA), ethylenglycol-bis-(beta-amino-ethylether)-N,N'tetraacetic acid (EGTA), cyclohexane-diaminetetraacetic acid (CDTA) and diethylentria-minepentaacetic acid (DTPA) on the distribution and excretion of intraperitoneally injected strontium were investigated in male Swiss mice. Strontium nitrate was given at a dose equal to 3.78 mmol/kg and ten minutes after, chelators were administered intraperitoneally at doses approximately equal to one-fourth of their respective LD50 values. DTPA, followed by CDTA, EDTA and tartaric acid, was consistently the most effective in increasing the urinary excretion of strontium. Only ascorbic acid increased significantly the fecal excretion of strontium. CDTA, DTPA and ascorbic acid were also the most effective chelators in reducing the concentration of strontium found in various tissues. CDTA, DTPA and tartaric acid are the most effective agents of those tested in the removal of strontium after a single administration.

Animals↗