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PubMed1993

[Treatment of symptomatic bone metastases of prostatic carcinoma using strontium chloride (Sr-89)].

Until now, patients with a progressive prostatic cancer, in whom all therapies failed and the disease spread locally and distally, was considered "a lost patient"; because it did not exist an effective therapy easily to be used. The skeletal pain control is a serious problem and it is a great responsibility also for the Urologists especially if the patient has not a short survival time and the quality of life is very poor. Physicians feel the need for a systemic, well tolerated and effective therapy also for a long time, uniform and repeatable, able to be efficient for these patients. Strontium 89 chloride seems to offer all these possibilities and to be the best procedure for Urologist, Radiotherapists and Nuclear Specialists in order to satisfy the patients requirements. International research has shown Sr-849 Chloride is a powerful new therapy. Sr-89 Chloride is a radiopharmaceutical product for the treatment of painful metastases from prostatic cancer. It is a new treatment but its effectiveness is well documented and results are reported in the most important international literature. In our Department a clinical research has started and our purpose is to produce more data for a clinical and biological evaluation of the results, hoping that a similar research will extend as a multicenter study.

Bone Neoplasms↗

PubMed2006

Early African Diaspora in colonial Campeche, Mexico: strontium isotopic evidence.

Construction activities around Campeche's central park led to the discovery of an early colonial church and an associated burial ground, in use from the mid-16th century AD to the late 17th century. Remains of some individuals revealed dental mutilations characteristic of West Africa. Analyses of strontium isotopes of dental enamel from these individuals yielded unusually high (87)Sr/(86)Sr ratios, inconsistent with an origin in Mesoamerica, but consistent with an origin in West Africa in terrain underlain by the West Africa Craton, perhaps near the port of Elmina, a principal source of slaves for the New World during the 16th century. These individuals likely represent some of the earliest representatives of the African Diaspora in the Americas.

Africa, Western↗

PubMed1975

The effect of strontium, cobalt and fluoride on rat incisor enamel formation.

This investigation examined ultrastructurally the entire period of development of alterations in formative ameloblasts and the enamel which they produce following injection with fluoride, strontium, and cobalt ions. Rats injected with these ions were sacrificed at intervals of 1, 2, 4, 8, 16, 24 and 48 hours to elucidate the sequence and detail of cytologic and cell product alterations which occur. Undecalcified sections of rat incisor teeth were studied using electron microscopy and microradiography. All three ions initially produced disturbances in cell morphology and enamel formation consisting of dark globules, vacuoles, and pooling of stippled material on the enamel surface. While a period of decreased crystal formation occurred after injection with all three ions, only cobalt responses included a period of apparently complete absence of crystal formation. The hypermineralized layers occurring in the altered enamel are attributed to changes in the rate of enamel matrix formation and duration of its exposure to tissue fluids. Morphologic changes in Tomes' process were observed at the time of formation of abnormel following injection of all three ions. These observations are compared with previous studies of altered enamel formation and analyzed with the goal of learning more about the mechanisms of amelogenesis.

Ameloblasts↗

PubMed2004

In vivo cancellous bone remodeling on a strontium-containing hydroxyapatite (sr-HA) bioactive cement.

The purpose of this study was to investigate the in vivo bone response to the strontium-containing hydroxyapatite (Sr-HA) bioactive bone cement injected into the cancellous bone. Sr-HA cement was injected into the iliac crest of rabbits for 1, 3, and 6 months. Active bone formation and remodeling were observed after 1 month. Newly formed bone was observed to grow onto the bone cement after 3 months. Thick osteoid layer with osteoblasts formed along the bone and guided over the bone cement surface reflected the stimulating effect of Sr-HA. From scanning electron microscopy (SEM) and energy-dispersive X-ray (EDX) analysis, high calcium and phosphorus levels were detected at the interface with a thick layer of 70 microm in width, and fusion of Sr-HA with the bone was observed. Blood vessels were found developing in remodeling sites. The affinity of bone on Sr-HA cement was increased from 73.55 +/- 3.50% after 3 months up to 85.15 +/- 2.74% after 6 months (p < 0.01). In contrast to Sr-HA cement, poly(methyl methacrylate) (PMMA) bone cement was neither osteoconductive nor bioresorbable. Results show that the Sr-HA cement is biocompatible and osteoconductive, which is suitable for use in treating osteoporotic vertebral fractures.

Animals↗

PubMed2004

Ultrastructural study of mineralization of a strontium-containing hydroxyapatite (Sr-HA) cement in vivo.

The purpose of this study was to investigate the mineralization leading to osseointegration of strontium-containing hydroxyapatite (Sr-HA) bioactive bone cement injected into cancellous bone in vivo. Sr-HA cement was injected into the ilium of rabbits for 1, 3, and 6 months. The bone mineralization area was found to be largest at 3 months, then at 1 month, and smallest at 6 months (p < 0.01) measured with tetracycline labeling. Osseointegration of Sr-HA cement was achieved at 3 months as observed by scanning electron microscopy. A high calcium and phosphorus area was observed at the interface of bone-Sr-HA cement determined by energy-dispersive X-ray analysis. Transmission electron microscopy gave evidence of the mechanism of bone formation. Dissolution of Sr-HA into debris by the bone remodeling process was thought to increase the concentration of calcium and phosphorus at the interface of bone-Sr-HA cement and stimulate bone formation. Crystalline Sr-HA formed an amorphous layer and dissolved into the surrounding solution, then apatite crystallites were precipitated and formed new bone at 3 months. This young bone then becomes mature bone, which bonds tightly to the Sr-HA cement with collagen fibers inserted perpendicularly after 6 months.

Animals↗

PubMed2006

Osteoprecursor cell response to strontium-containing hydroxyapatite ceramics.

The objective of this study was to investigate the in vitro bioactivity of strontium-containing hydroxyapatite (Sr-HA), and its effect on cellular attachment, proliferation, and differentiation. The effect of Sr-HA has been compared with that of hydroxyapatite (HA), which is widely used in orthopedics and dentistry. Sr-HA ceramic containing 10 mol % was prepared. The bioactivity of Sr-HA was evaluated in vitro by immersion in simulated body fluid (SBF). After immersion in SBF, Sr-HA exhibited greater ability to induce apatite precipitation on its surface than did HA. The possible effects on cell behavior of Sr-HA were examined by culturing osteoprecursor cells (OPC1) on materials surfaces. Cell shape and cell-material interactions were analyzed by scanning electron microscope (SEM) and the MTT assay was used to determine cell proliferation on samples. When compared with HA, Sr-HA promoted better OPC1 cell attachment and proliferation, and showed no deleterious effects on extracellular matrix formation and mineralization. Confocal scanning microscopy was used to assess the expression of specific osteoblast proteins: alkaline phosphatase (ALP) and osteopontin (OPN). The results obtained indicate that the presence of Sr stimulates OPC1 cell differentiation, and enhances ALP and OPN expression.

Alkaline Phosphatase↗

PubMed2004

Surface treatment of injectable strontium-containing bioactive bone cement for vertebroplasty.

A novel injectable bioactive bone-bonding cement (SrHAC) composed of strontium-containing hydroxyapatite (Sr-HA) as the inorganic filler and bisphenol A diglycidylether dimethacrylate (Bis-GMA) as the organic matrix for vertebroplasty was developed previously. In this study, the Sr-HA powders were surface treated with methyl methacrylate (MMA) to improve the interface integration of the two phases. After surface treatment, the compression strength and Young's modulus, which were tested after immersion in distilled water at 37 degrees C for 24 h according to ISO 5833, were increased by 68.65 % (p <.001) and 31.02% (p <.001), respectively. The bending strength and bending stiffness of the bioactive bone cement were significantly improved by 54.44% (p <.001) and 83.90% (p <.001). In addition, the handling property of the cement was also enhanced. In vitro biomechanical testing showed that the stiffness of the fractured spine recovered to 82.5% (p <.01) of the intact condition after cementation with surface-treated SrHAC. The failure load of the spine cemented with original and MMA-treated SrHAC improved by 14.25% (p <.05) and 46.91% (p <.05) in comparison with the fractured spines. Results from this study revealed that the MMA-treated SrHAC has a better mechanical effect for orthopedic applications.

Animals↗

PubMed2006

Strontium-containing hydroxyapatite (Sr-HA) bioactive cement for primary hip replacement: an in vivo study.

The purpose of this study was to evaluate the strontium-containing hydroxyapatite (Sr-HA) cement in primary hip replacement, using a rabbit model, and to investigate the histological findings at the cement-implant and bone-cement interfaces under weight-bearing conditions. Unilateral hip replacement was performed with Sr-HA cement or polymethylmethacrylate (PMMA) cement in rabbits and observations were made after 6 months. Good fixation between the Sr-HA cement and implant was observed. Osseointegration of the Sr-HA cement with cancellous bone was widespread. Many multinucleus cells covered the surface of the cement, and resorbed the superficial layer of the cement. By scanning electron microscopy (SEM) and energy-dispersive X-ray (EDX) analysis, high calcium and phosphorus levels were detected at the interface with a thickness of about 10 microm. Intimate contact was also observed between the Sr-HA cement and cortical bone without fibrous layer intervening. The overall affinity index of bone on Sr-HA cement was (85.06 +/- 5.40)%, which is significantly higher than that on PMMA cement (2.77%+/- 0.49%). On the contrary, a fibrous layer was consistently observed between PMMA cement and bone, and PMMA cement evoked an inflammatory response and foreign body reaction in the surrounding bony tissues. Results suggested good bioactivity and bone-bonding ability of the Sr-HA cement under weight-bearing conditions.

Animals↗

PubMed1987

Use of strontium to separate calcium-dependent pathways for proliferation and differentiation in human keratinocytes.

The role of extracellular calcium (Caex) in modulating keratinocyte differentiation has been well documented, but its role in proliferation has been harder to define due to the confounding effect of terminal differentiation. Because strontium (Sr) does not induce terminal differentiation in murine keratinocytes but does mimic the stimulatory effect of Caex on DNA synthesis in chick fibroblasts, experiments were undertaken to determine if Sr could be used to separate the presumably opposing effects of Caex on the proliferation and differentiation of cultured human keratinocytes. In response to additions of SrCl2, keratinocytes in a serum-free hormone-supplemented basal medium containing 0.03 mM Ca showed a dose-dependent increase in day 7 cell yields. Cell yield in the optimal concentration of SrCl2 (1.8 mM) was approximately twice that obtained in any concentration of CaCl2. Maximally stimulatory additions of CaCl2 varied from 0.05 to 1.8 mM, but 0.03 and 0.05 mM additional CaCl2 always increased cell yield relative to unsupplemented controls. Keratinocytes grown in low levels of CaCl2 or any level of SrCl2 have minimal contact with each other regardless of cell density in contrast to the colonies of tightly apposed and stratified cells grown in 1.8 mM CaCl2. Transmission electron micrographs of vertically sectioned confluent cultures in low or high levels of SrCl2 or in low levels of CaCl2 revealed abundant ribosomes and keratin filaments but no stratification or desmosomes, while cultures in 1.8 mM CaCl2 were stratified with numerous desmosomes. These results suggest that Caex may separately stimulate keratinocyte proliferation and terminal differentiation and that Srex can substitute for Caex in the former but not the latter process.

Calcium↗

PubMed1985

Selectively eliminated blood monocytes and splenic suppressor macrophages in mice depleted of bone marrow by strontium 89.

The contribution of specific activity to the effects of the bone-seeking isotope, strontium 89 on radiosensitive components of mononuclear phagocyte populations was investigated in mice. CBA/J mice received a fixed dose of 2 microCi/g body weight of 89Sr with three different specific activities, 6 Ci, 100 microCi and 20 microCi per mg Sr. The estimated radioactivity located in the bone surface was 4,200, 3,000 and 2,400 cpm/mg bone when measured 2 days after the administration of 89Sr, and was lost with an estimated biological half-life of 27, 25, and 23 days, respectively. Bone marrow suppression was assessed by quantitation of the depletion of macrophage-colony forming cells (M-CFC) grown in vitro in the presence of macrophage growth factor. The decline in M-CFC closely paralleled the level of radioactivity in the bone. These effects were clearly reflected by the depletion of monocytes in the blood, which were reduced to 14%, 14%, and 21% of control levels corresponding to SA's of 6 Ci/mg, 100 microCi/mg and 20 microCi/mg when counted on day 10. By day 30 the respective monocyte levels were 15%, 31%, and 77%. Furthermore, the induction of prostaglandin E producing suppressor macrophages (M phi) by Corynebacterium parvum administration was found to vary inversely with the effects of radioactivity in the bone, with initial impairment followed by quantitative recovery. Resident-type M phi in peritoneal cavity, however, appear to be unaffected by 89Sr-treatment. These data suggest, as before, that the monocytes and suppressor M phi are dependent on radiosensitive marrow cells. The observations also lead to the conclusion that the specific activity of 89Sr preparations is an important determinant of the degree of suppression and of the rate of recovery of bone marrow from the effects of irradiation that follow the administration of this isotope.

Animals↗

PubMed1991

Developmental potential and chromosome constitution of strontium-induced mouse parthenogenones.

The brief exposure of recently ovulated mouse oocytes to M16 embryo culture medium supplemented with strontium chloride (M16 Sr2+) for 2-10 min was observed to induce a high incidence of parthenogenesis. A lower incidence of activation and a significant rate of oocyte degeneration was observed when oocytes were incubated in M16 Sr2+ medium for 20-60 min. The majority of the oocytes exposed to this agent for 2-10 min developed as single-pronuclear haploid parthenogenones. The incidence of this parthenogenetic class was reduced as the duration of exposure to M16 Sr2+ was increased from 2 to 30 min. Under these conditions a greater proportion of the activated oocytes developed as two-pronuclear diploid parthenogenones, due to failure of second polar body extrusion. The activation frequency and the proportionate incidence of the pathways of parthenogenetic development observed following the exposure of ovulated oocytes to calcium-free M16 medium differed significantly from that induced by exposure to M16 Sr2+. Cytogenetic analysis of the single-pronuclear haploid class of Sr(2+)-induced parthenogenones at metaphase of the first-cleavage mitosis has shown that this agent did not induce a significant increase in the incidence of chromosome segregation errors during the completion of the second meiotic division. Analysis of the developmental potential of the two-pronuclear class of diploid Sr(2+)-induced parthenogenones during the preimplantation stages of embryogenesis revealed that their cell number and rate of cell division were less than those of fertilised embryos retained either in vivo or in vitro. The novel methods of activating oocytes indicated in this study present new opportunities to improve the efficiency of embryo cloning techniques with the ruminant species.

Animals↗

PubMed1994

An overview of current clinical experience with strontium-89 (Metastron).

Prostate cancer is one of the most common tumors in men. At presentation, 50% of patients have advanced disease and 25% have bone metastases. Hormonal palliation is the treatment of choice for metastatic bone pain, with a pain-free response rate of 75% for a period of 16-18 months. Second-line treatment with chemotherapy has a moderate and short-term effect. Once endocrine therapy and chemotherapy cease to be effective, radiotherapy is a good option for recurrent painful bone metastases. Diffuse painful metastases can be treated with half-body irradiation with a response rate of up to 70%, but there is considerable toxicity. Strontium-89 (Metastron) is a calcium analog radionuclide that is selectively absorbed at bone locations with increased osteoblastic activity. It is a pure beta-emitter with bone penetration of 0.8 cm, and it has been used in multiple trials with response rates of up to 80%. Results are reported with Metastron in 28 patients with diffuse painful bone metastases, in whom a response rate of 82% was seen.

Aged↗

PubMed2000

Loading of calcium and strontium into the sarcoplasmic reticulum in rat ventricular muscle.

Previous work suggests that strontium ions (Sr(2+)) are less effective than calcium ions (Ca(2+)) at supporting excitation-contraction (EC) coupling in cardiac muscle. We therefore tested whether this was due to differences in the uptake and release of Ca(2+)and Sr(2+)by the sarcoplasmic reticulum (SR) of rat ventricular trabeculae and myocytes at 22-24 degrees C. In permeabilized trabeculae, isometric contractions activated by exposure to Ca(2+)- and Sr(2+)-containing solutions produced similar maximal force, but were four times more sensitive to Ca(2+)than to Sr(2+). The rate of loading and maximal SR capacity for caffeine-releasable Ca(2+)and Sr(2+)were similar. In isolated, voltage-clamped ventricular myocytes, the SR content was measured as Na(+)-Ca(2+)exchange current during caffeine-induced SR cation releases. The SR Ca(2+)load reached a steady maximum during a train of voltage clamp depolarizations. A similar maximal Sr(2+)load was not observed, suggesting that the SR capacity for Sr(2+)exceeds that for Ca(2+). Therefore, the relative inability of Sr(2+)to support cardiac EC coupling appears not to be due to failure of the SR to sequester Sr(2+). Instead, increases in cytosolic [Sr(2+)] seem to poorly activate Sr(2+)release from the SR.

Animals↗

PubMed1987

Strontium transport in the rat colon.

Concentration dependence of strontium (Sr) fluxes across the colon ascendens and descendens of the rat were measured in a modified Ussing-chamber. Mucosa (m) to serosa (s) and s to m Sr fluxes across both colonic segments were linearly related to the Sr concentration from 0.125 mmol/l to 10 mmol/l. In the colon ascendens m to s Sr fluxes were slightly higher than the fluxes in the opposite direction, resulting in net Sr absorption. In the colon descendens s to m fluxes were higher than the ms fluxes, resulting in net Sr secretion. Neither Sr nor calcium (Ca) showed a concentration dependent interaction with respect to their unidirectional fluxes in both parts of the colon. Only in the colon ascendens Sr at the highest concentration (10 mmol/l) inhibited m to s calcium transport. Experiments, in which the voltage dependence of the unidirectional Sr fluxes was measured confirmed the results obtained from the concentration dependence: The unidirectional fluxes of Sr across the colon ascendens and descendens were totally voltage dependent, i.e. diffusive. In the colon descendens the voltage dependence of the s to m flux was steeper than the flux from m to s. It is hypothesized that this prevalence is caused by an anomalous solvent drag effect. 1.25-Dihydroxyvitamin D3 [1.25 (OH)2D3] stimulated m to s calcium flux in the colon descendens but had no effect on Sr flux. The results demonstrate that Sr and Ca in the rat colon are transported by different mechanisms. In contrast to the Ca transport the Sr flux is only diffusive and insensitive to 1.25 (OH)2D3.

Action Potentials↗

PubMed1992

Changes in the linear attenuation coefficient of canine appendicular bone following intravenous infusion of strontium lactate, measured using gamma-ray computed tomography.

Changes in the average linear attenuation coefficient (LAC) within a fixed measurement volume in the proximal end of the dog tibia, which contains trabecular bone and associated soft tissues (the trabecular bone "space"), were monitored continuously using gamma-ray computed tomography (gamma-CT) prior to, during, and following intravenous infusion of strontium (Sr) lactate. An infusion of 1.3-4.7 g of Sr over a period of 110-160 minutes into 20-kg dogs resulted, within 6-8 hours, in an increase of 0.019-0.045 cm-1 (P less than 0.002) in the LAC. Calibration of the gamma-CT system showed that 0.44 mg/cm3 of Sr produced a change of 0.01 cm-1 in the LAC. Using this conversion factor, the Sr concentration in the trabecular bone space resulting from infusion, as measured by flame atomic absorption spectroscopy, agreed with that predicted by the change observed in the LAC. Sr present in the serum and urine was consistent with the changes observed in the LAC over the study period. Control dogs infused with mineral-free solutions showed no change in LAC. Calcium equivalents required to give the changes observed in the LAC using Sr indicate that variations in skeletal turnover in man can be monitored in the peripheral skeleton using gamma-CT.

Animals↗

PubMed1981

Radiation-induced meningeal and pituitary tumors in the rat after prenatal application of strontium-90.

Strontium-90 was inject i.v. into pregnant rats on day 18 post conception (p.c.). This caused a remarkable transplacental radioactivity uptake and accumulation in the ossification centers of the skull basis. The total radiation dose within the surface of these regions was consequently calculated to be 0.6-1.2 Gy within the entire lifespan. About 50% of it was delivered during the 7 days following the injection of the isotope. The pathologic examination of the offspring throughout their lifetime revealed a pituitary tumor frequency in the exposed groups which was about tenfold in the males and threefold in the females in comparison to the controls. A very outstanding result in the animals treated was the occurrence of metastasizing meningeal sarcomas in about 6% of all cases. In four cases (= 2%) the simultaneous occurrence of a pituitary adenoma and of a meningeal sarcoma could be observed.

Adenoma, Chromophobe↗

PubMed1988

Strontium as a tracer to study the transport of calcium in the epiphyseal growth plate (electronprobe microanalysis).

At the mineralization front of the epiphyseal growth plate large quantities of calcium (Ca) are necessary to form the mineral (a Ca-phosphate). It is an unsolved problem, whether Ca is transported through the cells of the growth plate cartilage or extracellularly. Electronprobe microanalysis (EPMA) allows the quantitative, morphologically correlated analysis of elements. EPMA can discriminate only different elements. To investigate the transport of Ca, Strontium (Sr) is a very good tracer, as it resembles Ca in many biological reactions. Our results demonstrate that the transport of Sr from the blood into the growth plate and through the growth plate needs only one or a few minutes. The measured intracellular Sr and Ca concentrations are much lower than the extracellular ones, while the intracellular Sr/Ca ratio is not or only a little bit lower than the extracellular one. It must be concluded, that significant amounts of Ca are neither transported through nor accumulated in the cells of the growth plate cartilage. The main transport is an extracellular diffusion. Using Sr as a tracer for Ca new results on the behaviour of Ca could be received.

Animals↗

PubMed1995

Bone pain palliation with strontium-89 in breast cancer patients with bone metastases and refractory bone pain.

Fifteen patients with breast cancer and skeletal metastases who had bone pain refractory to opioid analgesics and who were not eligible for or had not responded to local field radiotherapy, were treated with strontium-89. All patients had received previous treatment with chemotherapy and radiotherapy for bone metastases. Severity of bone pain, sleeping pattern, mobility and dependency on analgesics were evaluated before and 4, 8 and 12 weeks after 89Sr administration. Patients received 2 MBq/kg (118-148 MBq) of 89Sr by i.v. injection. Pain relief and a reduction in analgesic requirements were observed in 7 of the 15 (47%) patients, with a reduction in the severity score from 34% to 71%. Duration of the response varied from 3 to 7 months. A decrease in peripheral blood cell count was observed in 11 patients: a 15%-66% reduction in white cell count and a 14%-75% reduction in platelet count were detected at 12 weeks after treatment in these patients. We conclude that 89Sr is effective (47% response rate) for bone pain palliation in patients with bone metastases from breast cancer. Dependency on opioid analgesics may be reduced in patients with refractory bone pain.

Aged↗