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PubMed1978

The effect of fluoride and strontium application on dentin: in vivo and in vitro studies.

The effectiveness of topical 2% sodium fluoride applied with and without 10% strontium chloride pretreatment was compared in patients complaining of tooth hypersensitivity. In addition the radiopacity of 2% sodium fluoride and 25% strontium chloride treated dentin was studied in vitro. Reduction of sensitivity to cold and mechanical stimuli was evaluated during a period of 3 months by pain scoring in the exposed cervical dentin of homologous teeth on the two sides of the jaws. There was a significant decrease in the sensitivity of the exposed cervical dentin after treatment with sodium fluoride solution with or without pretreatment with strontium chloride solution. At the end of the experimental period the combined strontium and fluoride treatment was found to be more effective than that of fluoride alone in reducing sensitivity to cold. The increase in radiodensity of dentin samples immersed in strontium chloride was statistically significant, while there was no significant increase in density for the samples immersed in sodium fluoride solutions. A mineralization process is possibly the effective means by which fluoride or strontium diminishes sensitivity of dentin.

Adult↗
PubMed2000

Strontium as a marker for intestinal calcium absorption: the stimulatory effect of calcitriol.

BACKGROUND: Intestinal strontium absorption is becoming accepted as a clinical and diagnostic tool for assessing intestinal calcium absorption in humans. However, little is known about whether intestinal strontium absorption, like that of calcium, is stimulated by calcitriol in healthy humans. METHODS: The effect of calcitriol on intestinal strontium absorption was measured in eight healthy men, ages 20-60 years. Before administration of calcitriol, two tests were performed with an interval of 10 days for calculating the within-subject variation (SE(R)). Before the third test, 0.5 microg of calcitriol was given twice daily for 3 days. In each test, the fractional strontium absorption (Fc(240)) and the area under the concentration-time curve (AUC(0-240)) 4 h after an oral strontium load of 2.5 mmol were calculated. RESULTS: The within-subject SE(R) of Fc(240) and AUC(0-240) was 1.7 +/- 0.7 and 0.83 +/- 0.1, respectively. The stimulatory effect of calcitriol on Fc(240) and AUC(0-240) was 35% (21.8 +/- 2.0 to 28.8 +/- 2.4; P = 0.003) and 61% (8.97 +/- 0.97 to 14.4 +/- 1.3 mmol. L(-1). min; P = 0.001), respectively. CONCLUSIONS: Although the reproducibility of AUC(0-240) and its sensitivity to calcitriol were better than those of Fc(240), the Fc(240) of strontium is preferred for a clinical test because of its simplicity, requiring only two instead of five blood samples.

Adult↗
PubMed1978

Nickel and strontium distribution in some mouse tissues. Passage through placenta and mammary glands.

Radioactive isotopes of strontium or nickel (89Sr and 63Ni) were injected ip as chlorides on adult female mice and the distribution and retention studied in several soft and hard tissues, including tissues of fetuses and sucklings. The strontium concentration was comparable in liver, kidney and heart and higher than that of brain tissue. The acid soluble part of the mineralized tissues showed a strontium concentration 100-1000 times that of the soft tissues. Progeny receiving strontium through placenta or through mammary glands showed a distribution pattern similar to that of their mother, with retention of strontium in mineralized tissue. The nickel concentration was larger in the kidney than in other organs investigated. No nickel affinity was found for mineralized tissues. Nickel was readily passed through placenta and mammary glands. Contrary to findings for strontium, the nickel concentration in tissues of fetuses was higher than that of their mother.

Animals↗
PubMed1995

Intestinal calcium absorption as shown by stable strontium test in celiac disease before and after gluten-free diet.

OBJECTIVES: To investigate the effect of gluten-free diet on mineral and bone metabolism in women with celiac disease and, using the strontium test, to assess intestinal calcium absorption. METHODS: We studied body mass index, biochemical and bone mineral indices, strontium absorption test, and bone mineral density in 18 women (mean age 36.8 yr, range 18-68 yr) with celiac disease at diagnosis and after 12 months of gluten-free diet. RESULTS: Mean strontium absorption at diagnosis was markedly decreased with respect to control values (13.84 +/- 9.03% vs 22.47 +/- 4.21%, p < 0.0001), and 11 of the 18 patients (61%, subgroup A) had low values. In all patients, mean hemoglobin, serum potassium, magnesium, plasma calcium, urinary calcium, and phosphorus were significantly abnormal at diagnosis, whereas only the subgroup A had significantly reduced body mass index, 25 OH vitamin D, and elevated alkaline phosphatase. This subgroup differed in body mass index (p < 0.003) and calciuria (p < 0.035) with respect to the other patients. Strontium absorption correlated with body mass index, calcemia, and 25 OH vitamin D. After the gluten-free diet, all biochemical variables and strontium absorption normalized (23.23 +/- 5.54%), whereas bone mineral density did not change. CONCLUSIONS: At diagnosis, the patients frequently had intestinal calcium malabsorption, as demonstrated by strontium test, with an early renal compensatory mechanism. After the gluten-free diet, the normalization of calcium absorption and the decrease of mid-molecule parathyroid hormone suggested a normalization of mineral metabolism, although a positive effect on bone mineral density was not evident at that time.

Adult↗
PubMed1993

Strontium-89 as an adjuvant to external beam radiation improves pain relief and delays disease progression in advanced prostate cancer: results of a randomized controlled trial.

In a multicenter, randomized controlled trial involving 126 patients with endocrine-resistant advanced prostate cancer, all of whom received external beam radiotherapy, additional treatment with a single injected dose of 400 MBq strontium-89 (Metastron) significantly improved overall pain control. Adjuvant therapy with strontium-89 also significantly reduced analgesia requirements compared with placebo and delayed disease progression, as indicated by the requirement for further external beam radiotherapy. On certain measures, patients receiving strontium-89 also showed enhanced quality of life. Accompanying these changes, levels of prostate tumor markers were significantly reduced by strontium-89 treatment. The benefits resulting from adjuvant strontium therapy were associated with tolerable hematologic toxicity. The addition of strontium-89 to external beam radiation had no effect on survival. However, it has clear implications for improved palliation in advanced prostate cancer and may also impact positively on treatment costs.

Aged↗
PubMed1979

The action of strontium on basophil leukocytes and its use to probe the relationship between immunologic stimulus and secretory response.

Strontium will substitute for calcium in the activation of histamine secretion from human basophil leukocytes stimulated by an immunologic reaction or by the ionophore A23187. Strontium is required in 10-fold higher concentration (1 to 10 mM) to activate histamine release compared with calcium (0.1 to 1.0 mM). In terms of maximum release obtainable for a particular immunologic stimulus, strontium is more effective than calcium. Results are presented to show that calcium and strontium act at the same site but strontium is a more sensitive probe for that site. Strontium can be used to demonstrate that immunologic stimuli activate calcium-binding sites in basophils even when no secretion is observed in the presence of calcium. It is suggested that the degree of secretion observed from basophils depends on the number of occupied Fc receptors for IgE and the coupling of these Fc receptors to calcium transport sites.

Basophils↗
PubMed1996

Effects of the application of aluminium, strontium and magnesium solutions to the leaf surface of maize, and determinations of these elements by ICP-AES.

The uptakes of aluminium, magnesium and strontium through maize leaves were investigated. The plants were grown in the light and in the dark (etiolation). Samples of leaves were digested with a mixture of nitric acid and hydrogen peroxide, and measurements were made by ICP-AES. The aluminium, magnesium and strontium contents of control samples grown in the light or in the dark were found to be similar. There were significant increases in the contents of these elements after maize leaves were sprayed with aluminium, magnesium or strontium solutions: increases of 100 per cent for aluminium, 20 per cent for magnesium and 10 per cent for strontium. The uptakes of these elements were generally higher in the light than in the dark. Aluminium, magnesium and strontium ions act as antagonists of each other. The effects of spraying with the different solutions were also observed in the colour of the maize leaves. However, the ultrastructure of the leaves did not change. The formation of chlorophyll was accelerated by magnesium, and inhibited by aluminium or strontium.

Aluminum↗
PubMed2006

Strontium ranelate reduces the urinary level of cartilage degradation biomarker CTX-II in postmenopausal women.

OBJECTIVE: Strontium ranelate significantly decreases the risk of osteoporotic fractures. The objective of the present study was to investigate whether strontium ranelate (2 g/day) also affects cartilage brakedown as measured by urinary marker of cartilage degradation, designated CTX-II. METHODS: A subgroup of 2617 postmenopausal osteoporotic women (aged 75.7+/-4.4 years) were selected from the TROPOS phase III study on the basis of a urinary sampling reported at each visit during the first three years of the study. When included in TROPOS, they were randomized to strontium ranelate or placebo in a double-blind fashion for 3 years. A calcium and vitamin D supplement was also provided to the subjects during the study. A marker of collagen type II degradation (CTX-II) corrected for urinary creatinine (CTX-II/cr.) was assessed at regular intervals throughout the study in 1310 patients in strontium ranelate group and 1307 patients in placebo group. RESULTS: The response in CTX-II depended on time (p<0.0001), and this time dependency differed statistically significantly between groups (time x treatment) (p<0.0003). In addition, there was a statistically significant difference between treatments (p<0.0001). The difference in the response of CTX-II/cr. appeared already after three months, with the strontium ranelate-treated subjects having approximately 15-20% lower values than the placebo-treated subjects for the remaining study period (p<0.0001). CONCLUSION: Treatment with strontium ranelate significantly decreases urinary excretion of CTX-II, a marker of cartilage destruction. Further studies are warranted to investigate an effect on cartilage formation and symptoms of osteoarthritis.

Biomarkers↗
PubMed2005

Strontium as therapy for osteoporosis.

Osteoporosis is characterized by low bone mass and increased susceptibility to fracture. Recent in vitro studies showed that strontium ranelate, a novel agent containing two strontium atoms, acts as an effective anti-osteoporotic drug by inhibiting bone resorption by osteoclasts and promoting osteoblast replication and bone formation. Studies in animals demonstrated that strontium ranelate increases bone mass, microarchitecture and strength in intact rodents and prevents bone loss in osteopenic animals. Clinical studies show that strontium ranelate reduces the risk of vertebral and non-vertebral fractures in postmenopausal osteoporosis. Together, these recent advances point to unique effects of strontium ranelate on bone cells and show that strontium ranelate has significant clinical benefits in the treatment of postmenopausal osteoporosis.

Animals↗
PubMed1999

The effect of strontium oxide in glass-ionomer cements.

The reaction of strontium oxide powder with poly(acrylic acid) has been studied both alone and within glass-ionomer cements. Reaction was found to be slow and the strontium-carboxylate structure was found to be partially covalent in character, as determined by Fourier transform infrared spectroscopy (FTIR). These are similar to the structures formed by calcium in glass-ionomer cements, but are different from typical monomeric strontium carboxylates, which tend to be purely ionic. Strontium oxide powder introduced in two types of glass-ionomer cements, slowed down the setting reaction at both 21 degrees C and 37 degrees C, but at low levels (5 wt %), increased the compressive strength in both cement formulations studied. However, at higher levels, it was found to decrease the compressive strength. This study confirms the view that strontium is a cement-forming ion; but concludes that, except at very low levels, strontium oxide powder does not improve the properties of glass-ionomer cements.

Journal Article↗
PubMed2006

Strontium ranelate: a dual mode of action rebalancing bone turnover in favour of bone formation.

The increased bone remodeling in women after menopause induces an imbalance between bone resorption and formation, leading to decreased bone mass, altered bone microarchitecture, and increased fracture risk. Current antiosteoporotic drugs decrease bone remodeling or increase bone formation. Strontium ranelate (Protelos) is a newly developed antiosteoporotic drug that acts by reducing bone resorption and promoting bone formation, thereby inducing a positive bone balance. In rat and mouse culture models, strontium ranelate enhances preosteoblastic cell replication and bone formation markers. In contrast, it decreases rodent osteoclastic cell resorbing activity and human osteoclast differentiation, and increases rabbit osteoclast apoptosis. In vivo, strontium ranelate increases bone formation and reduces bone resorption in mice, resulting in increased vertebral bone mass. In rats, strontium ranelate increases bone mass and improves microarchitecture and bone geometry, resulting in increased bone resistance. In ovariectomized rats, strontium ranelate decreases bone resorption but maintains high bone formation, resulting in improved bone microarchitecture and increased bone mass and strength. In clinical trials, serum alkaline phosphatase levels increased whereas serum CTX levels simultaneously decreased in patients treated with Protelos versus placebo at all time-points. In these trials, histomorphometric analysis of bone biopsies showed that the osteoblast surface and mineral apposition rate increased whereas bone resorption parameters tended to decrease in treated patients compared to the placebo group. These preclinical and clinical data indicate that strontium ranelate acts by increasing bone formation and decreasing bone resorption, thus rebalancing bone turnover in favour of bone formation, an effect that results in increased bone mass and strength.

Animals↗
PubMed2006

Vertebral fracture risk reduction with strontium ranelate in women with postmenopausal osteoporosis is independent of baseline risk factors.

UNLABELLED: Strontium ranelate (2 g/day) was studied in 5082 postmenopausal women. A reduction in incident vertebral fracture risk by 40% was shown after 3 years. This effect was independent of age, initial BMD, and prevalent vertebral fractures. INTRODUCTION: Strontium ranelate is an orally active treatment able to decrease the risk of vertebral and hip fractures in osteoporotic postmenopausal women. The aim of this study was to assess the efficacy of strontium ranelate according to the main determinants of vertebral fracture risk: age, baseline BMD, prevalent fractures, family history of osteoporosis, baseline BMI, and addiction to smoking. MATERIALS AND METHODS: We pooled data of two large multinational randomized double-blind studies with a population of 5082 (2536 receiving strontium ranelate 2 g/day and 2546 receiving a placebo), 74 years of age on average, and a 3-year follow-up. An intention-to-treat principle was used, as well as a Cox model for comparison and relative risks. RESULTS: The treatment decreased the risk of both vertebral (relative risk [RR] = 0.60 [0.53-0.69] p < 0.001) and nonvertebral (RR = 0.85 [0.74-0.99] p = 0.03) fractures. The decrease in risk of vertebral fractures was 37% (p = 0.003) in women <70 years, 42% (p < 0.001) for those 70-80 years of age, and 32% (p = 0.013) for those > or = 80 years. The RR of vertebral fracture was 0.28 (0.07-0.99) in osteopenic and 0.61 (0.53-0.70) in osteoporotic women, and baseline BMD was not a determinant of efficacy. The incidence of vertebral fractures in the placebo group increased with the number of prevalent vertebral fractures, but this was not a determinant of the effect of strontium ranelate. In 2605 patients, the risk of experiencing a first vertebral fracture was reduced by 48% (p < 0.001). The risk of experiencing a second vertebral fracture was reduced by 45% (p < 0.001; 1100 patients). Moreover, the risk of experiencing more than two vertebral fractures was reduced by 33% (p < 0.001; 1365 patients). Family history of osteoporosis, baseline BMI, and addiction to smoking were not determinants of efficacy. CONCLUSIONS: This study shows that a 3-year treatment with strontium ranelate leads to antivertebral fracture efficacy in postmenopausal women independently of baseline osteoporotic risk factors.

Bone Density↗
PubMed2005

High-field QCPMG NMR of strontium nuclei in natural minerals.

The only stable NMR-active isotope of strontium, (87)Sr, is a spin-9/2 quadrupolar nucleus that has a low gyromagnetic ratio, a low natural abundance, and a large nuclear electric quadrupole moment. In this work, we utilize the quadrupolar Carr-Purcell-Meiboom-Gill (QCPMG) pulse sequence and a 21.14 T NMR spectrometer at the Pacific Northwest National Laboratory to characterize the strontium sites in the natural minerals strontianite (SrCO(3)) and celestine (SrSO(4)). QCPMG at 21.14 T was found to provide sensitivity enhancements of roughly two orders of magnitude over Hahn-echo experiments at an 11.74 T magnetic field. We extracted the quadrupolar parameters for the strontium nuclei through iterative simulations of the experimental spectra with the SIMPSON program by Bak, Rasmussen, and Nielsen. The data show that the quadrupolar parameters of (87)Sr appear to be highly sensitive to the symmetry of the strontium coordination environment and can thus provide information about the strontium binding environment in complex systems.

Carbonates↗
PubMed1989

Bone strontium in pregnant and lactating females from archaeological samples.

Because plants and animals consume or absorb different amounts of strontium and calcium, anthropologists are able to use strontium/calcium (Sr/Ca) ratios from archaeologically recovered human bone to estimate the relative contributions of meat and plants to paleodiets. Often females exhibit higher Sr/Ca ratios than males, a fact usually attributed to lower meat intake among women. However, in vivo and in vitro experiments with laboratory animals show that pregnancy and lactation elevate maternal bone strontium and depress maternal bone calcium because 1) strontium is discriminated against in favor of calcium in the transport of ions to the placenta and mammary glands and 2) pregnancy and lactation facilitate absorption of alkaline earth metals from the gut. In this study, bone Sr/Ca ratios and strontium concentrations were compared between reproductive-age females, postmenopausal females, and adult males from two late prehistoric Native American sites in Georgia: the King site (N = 43) and the Etowah site (N = 51). At the King site, the mean Sr/Ca ratio of females was over 14% greater than that of males. At Etowah, the mean strontium level of reproductive-age females exceeded that of postmenopausal females by almost 25%. Most of the difference, it is argued, is due to pregnancy and lactation. A dietary preference among pregnant and lactating women for foods high in alkaline earths, particularly nuts and corn, may also be partially responsible. Until we assess the influence variables other than nutrition exert on trace element concentrations, our reconstructions of paleodiets will be suspect.

Adolescent↗
PubMed1986

Sr-89 therapy: strontium kinetics in disseminated carcinoma of the prostate.

Strontium kinetics were investigated in a group of 14 patients receiving 89Sr palliation for metastatic bone disease secondary to prostatic carcinoma. Using 85Sr as a tracer, total body strontium retention R(t) was monitored for a 3 month period following 89Sr administration, and at 90 days was found to vary from 11% to 88% and to correlate closely with the fraction of the skeleton showing scintigraphic evidence of osteoblastic metastatic involvement. Strontium renal plasma clearance varied from 1.6 l/day to 11.6 l/day, and in nine patients was significantly reduced compared with values found in healthy adult men, probably due to increased renal tubular reabsorption associated with the disturbance of calcium homoeostasis. Renal clearance rate was the principal factor determining R(t) for t less than 6 days, and was an important secondary factor at later times. Over the interval 30 days less than t less than 90 days, R(t) was closely fitted by the power law function R(t) = R30 (t/30)-b, with R30 and b showing the close correlation expected from the effect of R(t) on strontium recycling. The correction of the data for this effect to determine the true skeletal release rate is described. Measurement of localized strontium turnover in individual metastatic deposits from whole body profiles and scintigraphic images gave retention curves that typically rose to a plateau by 10 days after therapy, and then decreased very slowly. In contrast, retention curves for adjacent normal trabecular bone showed more rapid turnover, peaking at 1 day and subsequently decreasing following a t-0.2 power law function.(ABSTRACT TRUNCATED AT 250 WORDS)

Bone Neoplasms↗
PubMed2001

Mechanisms of action and therapeutic potential of strontium in bone.

The processes of bone resorption and formation are tightly governed by a variety of systemic and local regulatory agents. In addition, minerals and trace elements affect bone formation and resorption through direct or indirect effects on bone cells or bone mineral. Some trace elements closely chemically related to calcium, such as strontium (Sr), have pharmacological effects on bone when present at levels higher than those required for normal cell physiology. Indeed, strontium was found to exert several effects on bone cells. In addition to its antiresorptive activity, strontium was found to have anabolic activity in bone, and this may have significant beneficial effects on bone balance in normal and osteopenic animals. Accordingly, strontium has been thought to have potential interest in the treatment of osteoporosis. This review summarizes the mechanisms of action of strontium on bone cells, the evidence for its beneficial effects on bone mass in vivo, and its potential therapeutic effects in osteopenic disorders.

Animals↗
PubMed1991

A prospective, randomised double-blind crossover study to examine the efficacy of strontium-89 in pain palliation in patients with advanced prostate cancer metastatic to bone.

The palliative efficacy of strontium-89 chloride has been evaluated in a prospective double-blind crossover study comparing it with stable strontium as placebo in 32 patients with prostate cancer metastatic to bone. Response was assessed 5 weeks after each treatment. 26 patients were evaluable. Complete pain relief was only reported following strontium-89 injection. Statistical comparison between placebo and strontium-89 showed clear evidence of a therapeutic response to strontium-89 compared with only a limited placebo effect (P less than 0.01).

Aged↗
PubMed1988

Adjunctive radiotherapy with strontium-90 in the treatment of conjunctival squamous cell carcinoma.

Squamous cell carcinoma of the ocular conjunctiva is a relatively rare malignancy which is attended by a high rate of local recurrence following simple surgical excision. To date, the management of conjunctival squamous cell cancer has been controversial. From 1950 to 1985, 146 consecutive patients with superficial conjunctival squamous cell cancer were treated at the Queensland Radium Institute. All patients were treated by simple surgical excision of the visible conjunctival lesion followed by adjunctive radiotherapy. Of 140 patients with histologically confirmed squamous cell cancer, 123 were treated with a strontium-90 source, 10 with a radon "ring," and 7 with superficial X ray therapy. Standard policy since 1960 has been to deliver an incident dose of 30 Gy in a single fraction within the first 48 post-operative hours to the surgical bed using a strontium-90 source on a stand-off eye applicator. This report will largely focus on the 123 patients who were treated with a strontium-90 source, of whom 107 received 30 Gy, 14 received 40 Gy (pre 1960) and one patient each received 20 and 25 Gy incident dose. Of 131 evaluable patients, there were only 3 who developed local recurrence. All 3 local recurrences developed in elderly men who had presented with extensive superficial primary tumors. Two of the three recurrences occurred in the two patients who were treated with doses less than 30 Gy. Both early and late radiation-induced complications following ablative surgery and treatment with strontium-90 were very uncommon. Three patients developed unsightly conjunctival telangiectasia, 2 patients developed a persistent scleral ulcer and 2 patients developed clinically significant cataracts. This negligible degree of treatment-related side effects contrasts with the experience of 10 patients who had previously been treated with a radon ring, 8 of whom developed serious complications, although none developed local recurrence. On the basis of our excellent local control rates with minimal morbidity we would continue to advocate the use of simple surgical excision followed by 30 Gy beta radiation from a strontium-90 source as the definitive treatment for superficial conjunctival squamous cell cancer.

Adult↗