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PubMed1995

Strontium chloride Sr 89 for treating pain from metastatic bone disease.

The role of strontium chloride Sr 89 in the palliative treatment of pain associated with metastatic bone disease is reviewed. Conventional therapies to relieve metastatic bone pain include nonopioid and opioid analgesics, hormonal therapy, external-beam irradiation, and chemotherapy. Limitations in the long-term safety and effectiveness of these treatments have increased interest in using systemic radioactive isotopes for palliation of pain. Strontium chloride Sr 89 is a relatively new bone-seeking radiopharmaceutical that has FDA-approved labeling for use in relieving pain associated with skeletal metastases. An analogue of calcium, strontium chloride Sr 89 is rapidly cleared from the blood after i.v. injection. The agent selectively irradiates metastatic sites while generally sparing normal soft-bone tissue. In clinical studies, a majority of patients with prostate or breast cancer obtained substantial relief from bone pain after receiving strontium chloride Sr 89 alone or in combination with external-beam irradiation. Adverse effects tend to be mild, but patients should be monitored for possible hematologic toxicity. Patients should discontinue any calcium-containing products before receiving the agent. The typical dose is 4 mCi (148 MBq) administered by slow i.v. push over one to two minutes; doses can be repeated at three-month intervals. Pain relief usually begins in 10-20 days and lasts up to six months. Radiation safety measures are necessary in handling strontium chloride Sr 89 and the wastes of patients. Strontium chloride Sr 89 is costly, but preliminary analysis indicates that it may reduce management expenditures overall.(ABSTRACT TRUNCATED AT 250 WORDS)

Bone Neoplasms↗
PubMed2000

Acute myelogenous leukemia after exposure to strontium-89 for the treatment of adenocarcinoma of the prostate.

BACKGROUND: Strontium-89 is a pure Beta-emitting radioactive analogue of calcium that has been shown to be beneficial in the palliation of pain due to osseous metastases from adenocarcinoma of the prostate. The most significant reported toxicity is dose-related, reversible, myelosuppression characterized primarily by thrombocytopenia. METHODS: A report of two patients in whom acute myelogenous leukemia (AML) developed after treatment with strontium-89 and a review of the literature are presented. RESULTS: The two patients described in the current study developed AML 17 months and 26 months, respectively, after exposure to strontium-89 for the treatment of prostate carcinoma. To the authors' knowledge these patients represent the first two reported cases of AML after strontium-89 therapy for prostate carcinoma. CONCLUSIONS: The results of the current study suggest the leukemogenic potential of strontium-89 treatment in humans. To the authors' knowledge, the current study represents the first report of AML after therapeutic exposure to strontium-89. As this agent is used more frequently (and earlier in the disease course) in patients with prostate carcinoma, an increased incidence of secondary AML complicating the clinical management of patients with prostate carcinoma may be observed. [See editorial on pages 497-9, this issue.]

Adenocarcinoma↗
PubMed1989

89Sr therapy: strontium plasma clearance in disseminated prostatic carcinoma.

Strontium plasma clearance is an important factor determining the absorbed dose to metastases and bone marrow in patients receiving 89Sr radionuclide therapy for metastatic bone disease. Amongst male patients with disseminated prostatic carcinoma, the renal component of strontium clearance is frequently greatly reduced compared with values reported for healthy middle aged men. We report a study of renal and gut strontium plasma clearance, renal function, calcium urinary excretion, parathyroid function and extent of skeletal osteoblastic metastatic disease in patients referred for radiostrontium therapy for metastasised prostatic malignancy. The wide variation in net strontium clearance was principally due to variation in the renal component. Low values of strontium renal clearance were found to correlate with the elevation of serum PTH and nephrogenous cyclic AMP, which in turn correlated with extent of skeletal metastatic disease. This suggests that the osteosclerotic metastases characteristic of prostatic carcinoma induce secondary hyperparathyroidism due to the high avidity of the skeleton for calcium. The resulting reduction in strontium excretion may be beneficial to the objectives of radiostrontium therapy.

Bone Neoplasms↗
PubMed1989

Measurements of the strontium plasma clearance rate in patients receiving 89Sr radionuclide therapy.

The total strontium plasma clearance rate due to excretion through the kidneys and gut has an important influence on the absorbed does delivered to skeletal metastases and red bone marrow in patients receiving 89Sr radionuclide therapy for disseminated prostatic carcinoma. Although a measurement of the renal strontium plasma clearance rate may readily be obtained through a 24-h urine collection, little information is available on the correlation between renal and total clearances. We describe a method of determining total strontium plasma clearance rate from whole body counter measurements of total body strontium retention and measurements of plasma strontium concentration following administration of a 85Sr tracer dose at the time of 89Sr therapy. Amongst the 26 patients whom we studied, the total clearance rate varied from 1.2-15.0 l/day, renal clearance rate from 0.1-11.5 l/day, and the mean gut clearance rate was 2.0 l/day. A close correlation was found between total and renal clearance, with the renal component accounting for 96% of the variance in total strontium plasma clearance. A weak collection may exist between gut and renal clearance.

Humans↗
PubMed2003

Metastable equilibrium solubility behavior of carbonated apatite in the presence of solution strontium.

The purpose of this study was to use the concept of metastable equilibrium solubility (MES) to describe the anomalous solubility behavior of carbonated apatite (CAP) in the presence of solution strontium. A CAP sample (4.8 wt% CO(3), synthesized at 70 degrees C) was prepared by precipitation. Baseline MES distributions were determined in a series of 0.1 M acetate buffers containing only calcium and phosphate (no strontium) over a broad range of solution conditions. In order to assess the influence of strontium, MES profiles were then determined in a similar fashion with 20, 30, 40, 50, 60, 70, and 80% of the solution calcium being replaced on an equal molar basis by solution strontium. From the compositions of the equilibrating buffer solutions, ion activity products (IAPs) of the form Ca(10-n)Sr(n)(PO(4))(6)(OH)(2) (n = 0-10) were calculated in an attempt to determine the correct function governing the dissolution of the CAP preparation. The results demonstrate the following important findings: (a) at high solution strontium/calcium ratios (i.e., when 60% or more of the solution calcium was replaced by strontium), the MES profiles in all the experiments were found to be essentially superimposable when the solution IAPs were calculated using the stoichiometry of Ca(6)Sr(4)(PO(4))(6)(OH)(2), and (b), at low solution strontium/calcium ratios (i.e., when 40% or less of the solution calcium was replaced by strontium), the stoichiometry yielding MES data superpositioning was found to be that of hydroxyapatite. When other stoichiometries were assumed, good superpositioning of the data was not possible.

Apatites↗
PubMed1986

Interrelationships between the concentration of magnesium, calcium, and strontium in the hair of Japanese school children.

Inductively coupled atomic emission spectrometry was used for the determination of magnesium, calcium and strontium in the hair of Japanese school children (7-15 years of age, 158 males and 184 females). Sex-related differences in the levels of the three alkaline earth metals were observed (T-test, p less than 0.001). Geometric means (SD) of the concentrations of magnesium, calcium and strontium were 30.40 (1.42), 326.3 (1.62) and 0.509 (2.04) micrograms g-1 for males and 61.21 (1.73), 643.4 (1.57) and 2.749 (2.14) micrograms g-1 for females. For both sexes, significant positive correlations were observed between all concentration pairs of the three elements. The concentration ratios between any two of the three elements were also determined. The geometric mean of the concentration ratio of calcium to magnesium for males [10.73 (1.54)] is not significantly different from that for females [10.51 (1.40)] (T-test, p greater than 0.05). On the other hand, concentration ratios of magnesium to strontium [59.71 (1.99)] and calcium to strontium [640.9 (1.74)] for males are significantly higher (T-test, p less than 0.01) than those for females [22.27 (1.60) and 235.9 (1.65)]. The logarithmic-transformed ratio of magnesium to strontium has a strong positive correlation with the transformed ratio of calcium to strontium [r = 0.9529 (p less than 0.001) for males and r = 0.7284 (p less than 0.001) for females].

Adolescent↗
PubMed1985

Proteoglycans and glycosaminoglycans of normal and strontium rachitic epiphyseal cartilage.

An analytical protocol for the analysis of proteoglycans and proteins extracted from small sections of cartilage has been applied to the upper and lower parts of the epiphyseal growth plate of normal rats and rats with strontium-induced rickets. Only one polydisperse proteoglycan population was found in each of the four tissue portions. In strontium-induced rachitic animals the aggregability of proteoglycan monomers with hyaluronate was considerably increased in the lower part of the growth plate. The proteoglycans in the upper portion of the epiphysis contained somewhat less of chondroitin sulfate and keratan sulfate both in normal and strontium-induced rachitic rats. The chondroitin sulfate chains were somewhat larger in samples from strontium-induced rachitic rats compared with controls while in all groups about 90 per cent of the galactosamine in chondroitin sulfate was sulfated at position four. The findings of an altered composition of proteoglycans in strontium-induced rickets demonstrate that strontium not only prevents the mineral growth but may also induce the chondrocytes to produce a matrix with a different macromolecular composition.

Animals↗
PubMed2005

High-temperature sorption of cesium and strontium on dispersed kaolinite powders.

Sorption of cesium and strontium on kaolinite powders was investigated as a means to minimize the emissions of these metals during certain high-temperature processes currently being developed to isolate and dispose of radiological and mixed wastes. In this work, nonradioactive aqueous cesium acetate or strontium acetate was atomized down the center of a natural gas flame supported on a variable-swirl burner in a refractory-lined laboratory-scale combustion facility. Kaolinite powder was injected at a postflame location in the combustor. Cesium readily vaporized in the high-temperature regions of the combustor, but was reactively scavenged onto dispersed kaolinite. Global sorption mechanisms of cesium vapor on kaolinite were quantified, and are related to those available in the literature for sodium and lead. Both metal adsorption and substrate deactivation steps are important, so there is an optimum temperature, between 1400 and 1500 K, at which maximum sorption occurs. The presence of chlorine inhibits cesium sorption. In contrast to cesium, and in the absence of chlorine, strontium was only partially vaporized and was, therefore, only partially scavengeable. The strontium data did not allow quantification of global kinetic mechanisms of interaction, although equilibrium arguments provided insight into the effects of chlorine on strontium sorption. These results have implications for the use of sorbents to control cesium and strontium emissions during high-temperature waste processing including incineration and vitrification.

Adsorption↗
PubMed2006

Experimental and numerical iInvestigations of effects of silica colloids on transport of strontium in saturated sand columns.

Transport experiments with strontium were conducted using saturated sand columns in the presence and absence of silica colloids, and numerical modeling was performed with modeling results compared to experimental data. The experiments were aimed at testing the hypothesis that under certain chemical conditions colloids act as movement-retarding agents and yield a larger effective retardation factor for the migrating contaminant. Four individual experiments were conducted to identify conditions where the mobility of silica colloids is increased or decreased, and a similar set was conducted for strontium transport in the absence of colloids. Mobility of colloids was found to increase with decreasing ionic strength and increasing pH, with the ionic strength having the more significant impact. The reverse effect was obtained for strontium. Based on these results, two additional experiments were conducted where both colloids and strontium were injected at the column inlet. Results showed that under certain conditions of ionic strength and pH (I = 3.0 x 10(-2) M and pH = 4-5.4) colloids retarded the movement of strontium. The retardation effect was obtained in two experiments under slightly modified conditions, which confirms the role of colloids as retarding agents. Afinite difference numerical model was used to (a) simulate mobile breakthrough curves and compare to experimental data and (b) estimate the model parameters describing cotransport of strontium and colloids. The model accurately predicted arrival time and the overall shape of the breakthrough curves.

Colloids↗
PubMed2004

The effects of strontium ranelate on the risk of vertebral fracture in women with postmenopausal osteoporosis.

BACKGROUND: Osteoporotic structural damage and bone fragility result from reduced bone formation and increased bone resorption. In a phase 2 clinical trial, strontium ranelate, an orally active drug that dissociates bone remodeling by increasing bone formation and decreasing bone resorption, has been shown to reduce the risk of vertebral fractures and to increase bone mineral density. METHODS: To evaluate the efficacy of strontium ranelate in preventing vertebral fractures in a phase 3 trial, we randomly assigned 1649 postmenopausal women with osteoporosis (low bone mineral density) and at least one vertebral fracture to receive 2 g of oral strontium ranelate per day or placebo for three years. We gave calcium and vitamin D supplements to both groups before and during the study. Vertebral radiographs were obtained annually, and measurements of bone mineral density were performed every six months. RESULTS: New vertebral fractures occurred in fewer patients in the strontium ranelate group than in the placebo group, with a risk reduction of 49 percent in the first year of treatment and 41 percent during the three-year study period (relative risk, 0.59; 95 percent confidence interval, 0.48 to 0.73). Strontium ranelate increased bone mineral density at month 36 by 14.4 percent at the lumbar spine and 8.3 percent at the femoral neck (P<0.001 for both comparisons). There were no significant differences between the groups in the incidence of serious adverse events. CONCLUSIONS: Treatment of postmenopausal osteoporosis with strontium ranelate leads to early and sustained reductions in the risk of vertebral fractures.

Administration, Oral↗
PubMed1989

Electrical and mechanical effects of strontium in sheep cardiac Purkinje fibres.

The electrical and mechanical effects of strontium were studied in sheep cardiac Purkinje fibres perfused in vitro. In a nominally calcium free solution, strontium (1.35-10.8 mmol.litre-1): (1) caused a time, rate and concentration dependent shift of the plateau to more positive potentials, prolonged the action potential and decreased the maximum diastolic potential; (2) increased the time to peak and amplitude of the twitch and caused a tonic force which relaxed only on repolarisation; (3) was rapidly overcome in its effects by calcium (1.35-2.7 mmol.litre-1); (4) was antagonised by manganese (1 mmol.litre-1) and cadmium (0.1-0.2 mmol.litre-1); (5) was potentiated by noradrenaline (0.1 mumol.litre-1); (6) could induce action potentials in 27 mmol.litre-1 [K]o; (7) induced a tail following the action potential when the pacemaker potential had been blocked by caesium; (8) could induce a tail in 8 mmol.litre-1 [K]o which sustained force development and was reduced by calcium antagonists; (9) if applied to a quiescent fibre, induced a prolongation of the first resumed action potential and tonic force but a small twitch, and these effects were antagonised by calcium and manganese; and (10) induced a strong twitch after a period of quiescence in low [Na]o. It is concluded that the pronounced and progressive electrical and mechanical effects of strontium in cardiac Purkinje fibres are due to an enhanced strontium influx (due to inability of strontium to substitute for calcium in the inactivation of Isi) and to strontium extrusion through an electrogenic Na-Sr exchange.

Action Potentials↗
PubMed1991

The effect of nifedipine on the disposition of strontium gluconate used as a kinetic marker for calcium in healthy volunteers.

1. We have studied the disposition of stable strontium after the intravenous administration of strontium gluconate to eight healthy male volunteers both in control conditions and while they were taking the calcium antagonist nifedipine 10 mg three times daily. 2. Nifedipine, presumably by its action in blocking voltage-operated calcium channels, altered the in vivo disposition of strontium, causing large reductions in the half-life and the apparent volume of distribution of strontium. Total and renal clearances of strontium were unaltered by nifedipine. 3. These results support our previous suggestion that the delineation of strontium disposition can be used as a means of studying calcium disposition in vivo in man, and of studying the effects of drugs and diseases on that disposition.

Adult↗
PubMed2006

Preclinical assessment of gastrooesophageal tolerance of the new antiosteoporotic drug strontium ranelate: an endoscopic study in monkeys.

This study was aimed at evaluating the digestive tolerance of the new antiosteoporotic drug, strontium ranelate, and to compare it to that of another strontium salt, strontium chloride (SrCl2). Strontium ranelate, SrCl2, or placebo were administered orally (capsules) to 3 groups of 2 male and 2 female cynomolgus monkeys (Macaca fascicularis) once a day for 7 days at a dose of 2 g/day, which is the recommended therapeutic dose in man. Endoscopic examination of the oesophagus, the stomach and the first part of the duodenum was performed on fasted animals approximately 3 hr after the first (Day 1) and last dosing (Day 7), and, on Day 8 and Day 14 in case of lesions on Day 7. Strontium ranelate did not induce any acute or subchronic toxic effect on the gastric mucosa, the oesophagus and the first part of the duodenum. On the contrary, acute and superficial damages were noted on all animals receiving SrCl2 such as haemorrhagic and erosive lesions (formation of an ulcer in one male and a marked congestive antritis in one female). These effects were reversible after cessation of treatment. The microscopic examination of biopsies sampled at the site of gastric lesions revealed moderate granulocyte infiltration, indicating a local irritating origin of the lesions. Strontium ranelate by oral route is safe for the gastric mucosa while SrCl2 induced superficial and reversible lesions.

Administration, Oral↗
PubMed1971

Strontium accumulation by sarcoplasmic reticulum and mitochondria in vascular smooth muscle.

Electron-opaque deposits of strontium were observed in the sarcoplasmic reticulum and in mitochondria of spontaneously contracting vascular smooth muscles that had been incubated in a strontium-containing solution prior to fixation. The deposits were present in those elements of the sarcoplasmic reticulum that are in close contact with the surface membrane and also in more centrally located portions. In vascular smooth muscle that does not contract spontaneously, similar deposits of strontium were only seen if the muscle was depolarized during or glycerinated before exposure to the strontium-containing solution. Strontium was also deposited in the sarcoplasmic reticulum of the endothelium. It is suggested that translocation of calcium from the sarcoplasmic reticulum that is in close contact with the surface membrane, and now shown to accumulate divalent cations, is responsible for the action potential-triggered contractions of rabbit and guinea pig mesenteric veins. Strontium may also be a suitable marker for identifying sites that accumulate calcium in other types of cells in which translocation of calcium plays a major regulatory function.

Animals↗
PubMed2000

Strontium nitrate decreased histamine-induced itch magnitude and duration in man.

BACKGROUND: Previous studies have demonstrated that strontium salts have a potent and broad ability to suppress sensory irritation. OBJECTIVE: To ascertain the possible antipruritic effects of topical strontium salts, we conducted a double-blind randomized study to evaluate the effect of 20% strontium nitrate on itch magnitude (intensity) and duration. METHODS: In 8 human subjects, strontium nitrate was applied to the volar forearm and vehicle control to the contralateral volar forearm for 30 min; both substances were reapplied for an additional 5 min. Itch was then experimentally induced by intradermal injection of histamine. Itch magnitude was rated each minute for the first 20 min using a visual analogue scale (VAS). Itch duration in minutes was also recorded. RESULTS: Strontium nitrate, in comparison to its vehicle control, significantly shortened itch duration from 28.1+/-5.4 min (mean +/- SEM) to 18.5+/-4.2 min (p<0.01) and reduced itch magnitude at time points 12-20 min and overall (p<0.05). CONCLUSION: Strontium nitrate may act as a topical antipruritic agent in reducing histamine-mediated itch.

Adult↗
PubMed1983

Dental caries and strontium concentration in drinking water and surface enamel.

We investigated the possible cariostatic effect of strontium in the absence of effective amounts of fluoride by relating the DMFT index of the population to the strontium and fluoride concentrations in drinking water and enamel surfaces. The epidemiological survey was conducted in two neighboring districts in the northwest part of Greece, involving 582 children ranging in age from 11 to 14. The average DMFT values were 5.26 in the high-strontium (2.9-7 ppm Sr) area and 6.95 in the low-strontium (0.2-1.3 ppm Sr) area, while fluoride was low (less than 0.06 ppm) in both districts. Further, the average strontium concentration in surface enamel was higher in the high-strontium area.

Adolescent↗
PubMed1989

Strontium is required for statolith development and thus normal swimming behaviour of hatchling cephalopods.

When cephalopod eggs were incubated in artificial sea water it was found that they sometimes resulted in hatchlings with defects of the statocyst suprastructure, leading to the severe behavioural defect of uncontrolled swimming. Experiments in defined media (seven basic salts mixed in deionized water) with seven species of cephalopods demonstrated clearly that there is 100% normal development of the aragonite statoliths when strontium levels were 8 mg l-1. Conversely, statoliths did not develop when strontium was absent. In cuttlefish, the growth of the cuttlebone was also affected adversely when strontium was absent. In mariculture production tanks, supplementing commercial artificial sea water with strontium to normal levels of 8 mg l-1 almost eliminated the occurrence of abnormal hatchlings. Circumstantial evidence indicates that there is a critical window in development during which strontium is required for normal development. The role of strontium in biomineralization during embryogenesis is unknown, but it appears to be important in the Mollusca.

Animals↗
PubMed1994

Effects of strontium on calcium metabolism in rats. I. A distinction between the pharmacological and toxic doses.

Strontium at low doses has been used to treat osteoporosis. However, excessive doses can disturb calcium metabolism. The aim of the present study was to determine a dose that does not have any significant toxic effects on calcium contents in bone and calcium metabolism, and, consequently, to distinguish between pharmacological and toxic doses in rats. The rats were divided into a control, 0.05%-Sr, 0.10%-Sr and 0.50%-Sr groups (strontium intake approx. 0, 87.5, 175 and 875 mumol/day, respectively). All of the rats were pair-fed their respective diets containing various doses of strontium in single metabolic cages from when they were 36 to 63 days old. When the rats were 60 days old, bone formation, bone resorption, calcium balance and intestinal calcium absorption were calculated as calcium metabolic parameters over a 3-day period using calcium balance and kinetic studies. At the age of 64 days, the rats were sacrificed under anesthesia, and the femur and blood were collected. Calcium and strontium levels in the bone and serum were then measured. In the strontium groups that received less than 175 mumol/day, none of the calcium metabolic parameters were significantly affected. However, the calcium contents in the bone were significantly increased in the group that received 87.5 mumol/day group. On the other hand, in the group that received the highest dose of strontium (875 mumol/day), all of the calcium metabolic parameters measured were markedly suppressed. A decrease in calcium level in both the bone and serum was also observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗