Vitamin D supplementation and strontium ranelate absorption in postmenopausal women with low bone mass.

BACKGROUND: Strontium ranelate is used to treat osteoporosis. Calcium (Ca) and strontium (Sr) have common chemical features and are absorbed by the same pathways. Vitamin D has a main role in calcium intestinal absorption. The aim of this study was to investigate whether vitamin D status is a determinant of strontium ranelate absorption. METHODS: Twenty-five patients with vitamin D deficiency (25(OH)D<50 nmol/l) and 25 with vitamin D sufficiency (25(OH)D>75 nmol/l) underwent a 4-h oral Sr overload test. Sr absorption was evaluated as the fraction of absorbed dose and the area under the curve. After the baseline overload test, the deficient patients were treated until reaching sufficient vitamin D levels (25(OH)D>75 nmol/l) and the test was repeated. RESULTS: Changing vitamin D status from deficient to sufficient resulted in a significant increase in 1,25(OH)2D (24.97±4.64×34.62±9.14 pg/ml, P<0.001) and a reduction in parathyroid hormone (73.87±37.50×58.24±20.13 pg/ml, P=0.006). Nevertheless, no differences were found in the parameters used to evaluate Sr absorption between the vitamin D deficient and sufficient groups. In addition, vitamin D3 replacement in the deficient group did not result in enhanced Sr absorption. CONCLUSION: Vitamin D status did not interfere with strontium ranelate absorption. Taking into account the benefits of adequate vitamin D status in osteoporotic patients, we strongly recommend the treatment of vitamin D deficiency. However, the data demonstrate that such treatment does not enhance strontium ranelate absorption in patients with mild deficiency.

Strontium is incorporated in different levels into bones and teeth of rats treated with strontium ranelate.

The aim of this study was to evaluate the strontium incorporation into specific bones and teeth of rats treated with strontium ranelate. The relative strontium levels [Sr/(Ca + Sr) ratio] were obtained by synchrotron radiation micro X-ray fluorescence. The incisor teeth were further examined by energy dispersive X-ray spectroscopy (EDS) in a scanning electron microscope. The isolated mineral phase was investigated by EDS in a transmission electron microscope and X-ray diffraction. The strontium content was markedly increased in animals treated with strontium ranelate, with different incorporation levels found among specific bones, regions within the same bone and teeth. The highest strontium levels were observed in the iliac crest, mandible and calvaria, while the lowest were observed in the femoral diaphysis, lumbar vertebrae, rib and alveolar bone. The strontium content was higher in the femoral neck than in the diaphysis. The strontium levels also varied within the alveolar bone. High levels of strontium were found in the incisor tooth, with values similar to those in the iliac crest. Strontium was observed in both enamel and dentin. The strontium content of the molar tooth was negligible. Strontium was incorporated into the mineral substance, with up to one strontium replacing one out of 10 calcium ions within the apatite crystal lattice. The mineral from treated animals presented increased lattice parameters, which might be associated to their bone strontium contents. In conclusion, the incorporation of strontium occurred in different levels into distinct bones, regions within the same bone and teeth of rats treated with strontium ranelate.

Role of connexin 43 in the mechanism of action of alendronate: dissociation of anti-apoptotic and proliferative signaling pathways.

Bisphosphonates (BPs) inhibit osteocyte and osteoblast apoptosis via opening of connexin (Cx) 43 hemichannels and activating the extracellular signal regulated kinases ERKs. Previously, we hypothesized that intracellular survival signaling is initiated by interaction of BPs with Cx43. However, using whole cell binding assays with [(3)H]-alendronate, herein we demonstrated the presence of saturable, specific and high affinity binding sites in the Cx43-expressing ROS 17/2.8 osteoblastic cells, authentic osteoblasts and MLO-Y4 cells expressing Cx43 or not, as well as in HeLa cells lacking Cx43 expression and ROS 17/2.8 cells pretreated with agents that disassemble Cx channels. In addition, both BPs and the PTP inhibitor Na(3)VO(4) increased proliferation of cells expressing Cx43 or not. Furthermore, although BPs are internalized and inhibit intracellular enzymes in osteoclasts, whether the drugs penetrate non-resorptive bone cells is not known. To clarify this, we evaluated the osteoblastic uptake of AF-ALN, a fluorescently labeled analog of alendronate. AF-ALN was rapidly internalized in cells expressing Cx43 or not indicating that this process is not mediated via Cx43 hemichannels. Altogether, these findings suggest that although required for triggering intracellular survival signaling by BPs, Cx43 is dispensable for cellular BP binding, its uptake, as well as the proliferative effects of these agents.

Gastroresistant microparticles containing sodium alendronate prevent the bone loss in ovariectomized rats.

Sodium alendronate, an antiresorptive drug, primarily used in the treatment of osteoporosis was encapsulated in blended microparticles composed of Eudragit S100 and Methocel K15M. The micropowder obtained by spray-drying technique was characterized in terms of its morphology, particle size, encapsulation efficiency and in vitro drug release. In vivo studies were carried out in order to evaluate the pharmacodynamic effect and the ulcerogenic activity of sodium alendronate-loaded microparticles after oral administration in rats. Drug encapsulation efficiency was close to 80% and particle mean diameter of 13.8 microm. SEM analysis showed spherical collapsed shape particles with smooth surface. At pH 1.2, in vitro experiments showed that <10% of the drug was released from the microparticles. At pH 6.8, the microparticles were able to prolong the sodium alendronate release for 12h. In vivo experiments carried out in ovariectomized rats showed bone mineral density significantly higher for the sodium alendronate-loaded microparticles than for the negative control groups. Furthermore, the microencapsulation of the drug showed a significant reduction in the ulcerative lesion index. In conclusion, the blended microparticles are excellent oral carriers for sodium alendronate since they were able to maintain the drug antiresorptive effect and to reduce the gastrointestinal drug toxicity.

Calcitonin, sodium alendronate and high intensity laser in the treatment of traumatized teeth: a preliminary study.

The aim of this study was to evaluate the influence of erbium:yttrium-aluminum-garnet (Er:YAG) laser compared with traditional treatment on dentin permeability to calcitonin and sodium alendronate. Forty bovine roots were sectioned and divided into eight groups. Groups 1 and 2 (G1/G2) were immersed in saline solution; G1T/G2T were immersed in ethylene diamine tetra-acetic acid plus sodium lauryl ether sulfate (EDTA-T) and sodium hypochlorite (NaOCl); G1I/G2I were irradiated with Er:YAG laser (2.94 microm, 6 Hz, 40.4 J/cm(2)); G1TI/G2TI were immersed in EDTA-T, NaOCl and subjected to Er:YAG irradiation. After 4 h the radioactivity of the saline solution was measured. Statistical analysis revealed a significant difference (P < 0.05) when the groups treated with EDTA-T and NaOCl followed by Er:YAG laser irradiation were compared with the groups treated with EDTA-T only and with the groups that received no treatment. Er:YAG laser associated with traditional procedures significantly increased the diffusion of calcitonin and sodium alendronate through dentin. All groups showed calcitonin and sodium alendronate diffusion.

[Bioavailability of dietary calcium]. / Biodisponibilidade do cálcio dietético.

Dietary calcium (Ca) is fundamental to the bone's health. Both the purport and the element bioavailability in the food need to be considered. The purpose of this work was to summarize the factors involved in Ca absorption and point out the sources with higher bioavailability. Ca is mostly absorbed in the jejunum and low pH seems to favor its absorption, which is higher during growth, gestation/lactation and Ca and phosphorus (P) deficiency, and lower with aging. The richest and best-absorbed Ca source is cow's milk and its derivatives. Other foods show high Ca concentrations but variable bioavailability: foods rich in phytates and oxalates show a smaller absorption and carbohydrate-rich foods show higher absorption. Since Ca bioavailability in other animal's milk, soymilk and some vegetables is closer to that in cow's milk, adequate amounts of these foods could be used as an alternative.

Biodisponibilidade do cálcio dietético / Bioavailability of dietary calcium / Bioavailability of dietary calcium

O cálcio (Ca) dietético é fundamental para a saúde óssea. Tanto o teor como a biodisponibilidade do elemento nos alimentos devem ser considerados. Este artigo objetiva sumarizar os fatores envolvidos na absorção e destacar os alimentos com melhor disponibilidade do Ca. Este é absorvido principalmente no jejuno e o pH baixo parece favorecer sua absorção, que é maior no crescimento, na gestação/lactação e na carência de Ca ou fósforo (P), e menor no envelhecimento. As maiores fontes, e com melhor absorção, são os laticínios bovinos. Outros alimentos apresentam concentrações elevadas de Ca, mas com biodisponibilidade variável: os ricos em ácidos oxálico e fítico apresentariam uma menor absorção, enquanto que os ricos em carboidratos teriam uma absorção maior. Por apresentarem uma biodisponibilidade do Ca mais próxima da do leite bovino, o leite de outros animais, o de soja enriquecido e alguns vegetais, em quantidades adequadas, poderiam ser usados como alternativas a este.

Dietary calcium (Ca) is fundamental to the bone's health. Both the purport and the element bioavailability in the food need to be considered. The purpose of this work was to summarize the factors involved in Ca absorption and point out the sources with higher bioavailability. Ca is mostly absorbed in the jejunum and low pH seems to favor its absorption, which is higher during growth, gestation/lactation and Ca and phosphorus (P) deficiency, and lower with aging. The richest and best-absorbed Ca source is cow's milk and its derivatives. Other foods show high Ca concentrations but variable bioavailability: foods rich in phytates and oxalates show a smaller absorption and carbohydrate-rich foods show higher absorption. Since Ca bioavailability in other animal's milk, soymilk and some vegetables is closer to that in cow's milk, adequate amounts of these foods could be used as an alternative.