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1.
Dalton Trans ; 49(18): 5939-5948, 2020 May 14.
Article in English | MEDLINE | ID: mdl-32314772

ABSTRACT

Metal-based anion receptors have several important applications in sensing, separation and transport of negatively charged species. Amongst these receptors, di-zinc(ii) complexes are of particular interest for the recognition of oxoanions, in particular phosphate derivatives. Herein we report the synthesis of a di-zinc(ii) receptor and show that it has high affinity and selectivity for bisphosphonates such as alendronate and etidronate - which are used to treat a number of skeletal disorders as well as showing interesting anticancer properties. The binding mode of the di-zinc(ii) receptor with alendronate and etidronate has been unambiguously established by single crystal X-ray crystallography. In addition, by modifying the backbone of the receptor, we show that the drug-loaded receptor can be attached onto gold nanoparticles as potential drug-delivery vehicles.


Subject(s)
Bone Density Conservation Agents/analysis , Coordination Complexes/chemistry , Diphosphonates/analysis , Gold/chemistry , Metal Nanoparticles/chemistry , Zinc/chemistry , Coordination Complexes/chemical synthesis , Crystallography, X-Ray , Models, Molecular , Molecular Structure , Particle Size , Solutions , Surface Properties , Water/chemistry
2.
J Appl Oral Sci ; 27: e20180713, 2019.
Article in English | MEDLINE | ID: mdl-31691738

ABSTRACT

Vitamin D has been known to have important regulatory functions in inflammation and immune response and shows inhibitory effects on experimental periodontitis in animal models. However, the potential mechanism has yet to be clarified. Recent studies have highlighted Aryl hydrocarbon receptor (AhR) and its downstream signaling as a crucial regulator of immune homeostasis and inflammatory regulation. OBJECTIVE: This study aimed to clarify the effect of 1,25-dihydroxyvitamin D3 (VD3) on experimental periodontitis and AhR/nuclear factor-κB (NF-κB)/NLR pyrin domain-containing 3 (NLRP3) inflammasome pathway in the gingival epithelium in a murine model. METHODOLOGY: We induced periodontitis in male C57BL/6 wild-type mice by oral inoculation of Porphyromonas gingivalis (P. gingivalis), and subsequently gave intraperitoneal VD3 injection to the mice every other day for 8 weeks. Afterwards, we examined the alveolar bone using scanning electron microscopy (SEM) and detected the gingival epithelial protein using western blot analysis and immunohistochemical staining. RESULTS: SEM images demonstrated that alveolar bone loss was reduced in the periodontitis mouse model after VD3 supplementation. Western blot analyses and immunohistochemical staining of the gingival epithelium showed that the expression of vitamin D receptor, AhR and its downstream cytochrome P450 1A1 were enhanced upon VD3 application. Additionally, VD3 decreased NF-κB p65 phosphorylation, and NLRP3, apoptosis-associated speck-like protein, caspase-1, interleukin-1ß (IL-1ß) and IL-6 protein expression. CONCLUSIONS: These results implicate the alleviation of periodontitis and the alteration of AhR/NF-κB/NLRP3 inflammasome pathway by VD3 in the mouse model. The attenuation of this periodontal disease may correlate with the regulation of AhR/NF-κB/NLRP3 inflammasome pathway by VD3.


Subject(s)
Bone Density Conservation Agents/pharmacology , Calcitriol/pharmacology , NF-kappa B/drug effects , NLR Family, Pyrin Domain-Containing 3 Protein/drug effects , Periodontitis/drug therapy , Periodontitis/metabolism , Receptors, Aryl Hydrocarbon/drug effects , Alveolar Bone Loss , Animals , Blotting, Western , Bone Density Conservation Agents/analysis , Calcitriol/analysis , Caspase 1/analysis , Gingiva/drug effects , Gingiva/metabolism , Gingiva/pathology , Immunohistochemistry , Interleukin-1beta/analysis , Interleukin-6/analysis , Male , Mice, Inbred C57BL , NF-kappa B/analysis , NLR Family, Pyrin Domain-Containing 3 Protein/analysis , Periodontitis/pathology , Porphyromonas gingivalis , Receptors, Aryl Hydrocarbon/analysis , Reference Values , Reproducibility of Results , Treatment Outcome
3.
Nutrients ; 11(11)2019 Nov 08.
Article in English | MEDLINE | ID: mdl-31717258

ABSTRACT

The preventive effect of high-dose (9%) regular-fish oil (FO) against bone loss during aging has been demonstrated, but the effects of a low-dose (1%-4%) of a highly purified concentrated FO (CFO) has not been elucidated. The aim of this study was to determine the dose-dependent effect of a CFO against bone loss in C57BL/6 female mice during aging. Twelve-month old mice were fed with 1% and 4% CFO and 4% safflower oil (SFO) diets, including a group with a 4% regular-FO diet and a group with a lab chow diet for 12 months. Bone mineral density (BMD) was analyzed by dual-energy x-ray absorptiometry (DXA) before and after the dietary intervention. At the end of dietary intervention, bone resorption markers in serum and inflammatory markers in bone marrow and splenocytes and inflammatory signaling pathways in the bone marrow were analyzed. As compared to the 4% SFO control, 4% CFO maintained higher BMD during aging, while 1% CFO offered only a mild benefit. However, the 1% CFO fed group exhibited slightly better BMD than the 4% regular-FO fed group. BMD loss protection by CFO was accompanied by reduced levels of the bone resorption marker, TRAP, and the osteoclast-stimulating-factor, RANKL, without affecting the decoy-receptor of RANKL, osteoprotegerin (OPG). Further, CFO supplementation was associated with an increase in the production of IL-10, IL-12, and IFN-γ and a decrease in the production of TNF-α and IL-6, and the activation of NF-κB, p38 MAPK, and JNK signaling pathways. In conclusion, the supplementation of 4% CFO is very efficient in maintaining BMD during aging, whereas 1% CFO is only mildly beneficial. CFO supplementation starting at middle age may maintain better bone health during aging.


Subject(s)
Bone Density Conservation Agents/pharmacology , Bone Density/drug effects , Bone Remodeling/drug effects , Bone and Bones/drug effects , Dietary Supplements/analysis , Docosahexaenoic Acids/pharmacology , Eicosapentaenoic Acid/pharmacology , Osteoporosis/prevention & control , Age Factors , Animals , Bone Density Conservation Agents/analysis , Bone Marrow Cells/drug effects , Bone Marrow Cells/metabolism , Bone and Bones/diagnostic imaging , Bone and Bones/metabolism , Bone and Bones/physiopathology , Cells, Cultured , Cytokines/metabolism , Disease Models, Animal , Docosahexaenoic Acids/analysis , Eicosapentaenoic Acid/analysis , Female , JNK Mitogen-Activated Protein Kinases/metabolism , Mice, Inbred C57BL , Osteoporosis/diagnostic imaging , Osteoporosis/metabolism , Osteoporosis/physiopathology , Signal Transduction , p38 Mitogen-Activated Protein Kinases/metabolism
4.
Luminescence ; 34(3): 375-381, 2019 May.
Article in English | MEDLINE | ID: mdl-30884083

ABSTRACT

Sodium alendronate is the first in a pharmacological class known as bisphosphonates, used for treatment of various bone diseases. Assay of bisphosphonates by a spectroscopic technique is very challenging due to the fact that they lack chromophores and none of them are fluorescent. In this work, a simple method is presented for determination of alendronate in bulk and in pharmaceutical tablets using spectrofluorometry by exploiting the ability of alendronate to displace salicylate from the iron(III)-salicylate chelate, forming a non-fluorescent colorless iron(III)-alendronate complex. The liberated salicylate is fluorescent and is equivalent to the mount of alendronate added. The response was linear over the concentration range 20-90 µM and the proposed method was validated according to the guidelines of the International Conference on Harmonization. The correlation coefficient was found to be 0.995 and the limit of detection was 7.5 µM. The method was successfully applied for determination of alendronate in the commercially available Osteonate® tablets. The average percent recovery ± percent relative standard deviation was found to be 102.118 ± 2.033 which is congruent with the label claim of the dosage form. The results were also compared to a reported method using t-test and F-test at 95% confidence level; no significant differences were observed. The presented method is simple, fast, easy, cost-effective and suitable for routine pharmaceutical analysis.


Subject(s)
Alendronate/analysis , Bone Density Conservation Agents/analysis , Spectrometry, Fluorescence/methods , Fluorescence , Tablets/analysis
5.
J. appl. oral sci ; 27: e20180713, 2019. tab, graf
Article in English | LILACS, BBO - Dentistry | ID: biblio-1040234

ABSTRACT

Abstract Vitamin D has been known to have important regulatory functions in inflammation and immune response and shows inhibitory effects on experimental periodontitis in animal models. However, the potential mechanism has yet to be clarified. Recent studies have highlighted Aryl hydrocarbon receptor (AhR) and its downstream signaling as a crucial regulator of immune homeostasis and inflammatory regulation. Objective: This study aimed to clarify the effect of 1,25-dihydroxyvitamin D3 (VD3) on experimental periodontitis and AhR/nuclear factor-κB (NF-κB)/NLR pyrin domain-containing 3 (NLRP3) inflammasome pathway in the gingival epithelium in a murine model. Methodology: We induced periodontitis in male C57BL/6 wild-type mice by oral inoculation of Porphyromonas gingivalis (P. gingivalis), and subsequently gave intraperitoneal VD3 injection to the mice every other day for 8 weeks. Afterwards, we examined the alveolar bone using scanning electron microscopy (SEM) and detected the gingival epithelial protein using western blot analysis and immunohistochemical staining. Results: SEM images demonstrated that alveolar bone loss was reduced in the periodontitis mouse model after VD3 supplementation. Western blot analyses and immunohistochemical staining of the gingival epithelium showed that the expression of vitamin D receptor, AhR and its downstream cytochrome P450 1A1 were enhanced upon VD3 application. Additionally, VD3 decreased NF-κB p65 phosphorylation, and NLRP3, apoptosis-associated speck-like protein, caspase-1, interleukin-1β (IL-1β) and IL-6 protein expression. Conclusions: These results implicate the alleviation of periodontitis and the alteration of AhR/NF-κB/NLRP3 inflammasome pathway by VD3 in the mouse model. The attenuation of this periodontal disease may correlate with the regulation of AhR/NF-κB/NLRP3 inflammasome pathway by VD3.


Subject(s)
Animals , Male , Periodontitis/metabolism , Periodontitis/drug therapy , Calcitriol/pharmacology , NF-kappa B/drug effects , Bone Density Conservation Agents/pharmacology , NLR Family, Pyrin Domain-Containing 3 Protein/drug effects , Periodontitis/pathology , Reference Values , Calcitriol/analysis , Immunohistochemistry , Blotting, Western , Reproducibility of Results , Alveolar Bone Loss , NF-kappa B/analysis , Interleukin-6/analysis , Treatment Outcome , Receptors, Aryl Hydrocarbon/analysis , Receptors, Aryl Hydrocarbon/drug effects , Porphyromonas gingivalis , Caspase 1/analysis , Bone Density Conservation Agents/analysis , Interleukin-1beta/analysis , NLR Family, Pyrin Domain-Containing 3 Protein/analysis , Gingiva/drug effects , Gingiva/metabolism , Gingiva/pathology , Mice, Inbred C57BL
6.
Acta Pharm ; 68(2): 171-183, 2018 Jun 01.
Article in English | MEDLINE | ID: mdl-29702478

ABSTRACT

A reverse-phase HPLC (RP-HPLC) method was developed for strontium ranelate using a full factorial, screening experimental design. The analytical procedure was validated according to international guidelines for linearity, selectivity, sensitivity, accuracy and precision. A separate experimental design was used to demonstrate the robustness of the method. Strontium ranelate was eluted at 4.4 minutes and showed no interference with the excipients used in the formulation, at 321 nm. The method is linear in the range of 20-320 µg mL-1 (R2 = 0.99998). Recovery, tested in the range of 40-120 µg mL-1, was found to be 96.1-102.1 %. Intra-day and intermediate precision RSDs ranged from 1.0-1.4 and 1.2-1.4 %, resp. The limit of detection and limit of quantitation were 0.06 and 0.20 µg mL-1, resp. The proposed technique is fast, cost-effective, reliable and reproducible, and is proposed for the routine analysis of strontium ranelate.


Subject(s)
Bone Density Conservation Agents/analysis , Chromatography, High Pressure Liquid/methods , Chromatography, Reverse-Phase/methods , Thiophenes/analysis , Excipients/chemistry , Reproducibility of Results , Research Design
7.
Zhongguo Zhong Yao Za Zhi ; 42(21): 4246-4250, 2017 Nov.
Article in Chinese | MEDLINE | ID: mdl-29271167

ABSTRACT

The increasingly apparent liver injury problems of bone strengthening Chinese medicines have brought challenges for clinical application, and it is necessary to consider both effectiveness and safety in screening anti-osteoporosis Chinese medicines. Metabolic transformation is closely related to drug efficacy and toxicity, so it is significant to comprehensively consider metabolism-action/toxicity(M-Act/Tox) for screening anti-osteoporosis Chinese medicines. The current evaluation models and the number of compounds(including metabolites) severely restrict efficient screening in vivo. By referring to previous relevant research and domestic and abroad literature, zebrafish M-Act/Tox integrative method was put forward for efficiently screening anti-osteoporosis herb medicines, which has organically integrated zebrafish metabolism model, osteoporosis model and toxicity evaluation method. This method can break through the bottleneck and blind spots that trace compositions can't achieve efficient and integrated in vivo evaluation, and realize both efficient and comprehensive screening on anti-osteoporosis traditional medicines based on in vivo process taking both safety and effectiveness into account, which is significant to accelerate discovery of effective and safe innovative traditional Chinese medicines for osteoporosis.


Subject(s)
Bone Density Conservation Agents/analysis , Drugs, Chinese Herbal/analysis , Osteoporosis/drug therapy , Plants, Medicinal/chemistry , Animals , Bone Density Conservation Agents/metabolism , Drugs, Chinese Herbal/metabolism , Medicine, Chinese Traditional , Toxicity Tests , Zebrafish
8.
J Histochem Cytochem ; 64(10): 601-22, 2016 10.
Article in English | MEDLINE | ID: mdl-27666429

ABSTRACT

Minodronate is highlighted for its marked and sustained effects on osteoporotic bones. To determine the duration of minodronate's effects, we have assessed the localization of the drug in mouse bones through isotope microscopy, after labeling it with a stable nitrogen isotope ([(15)N]-minodronate). In addition, minodronate-treated bones were assessed by histochemistry and transmission electron microscopy (TEM). Eight-week-old male ICR mice received [(15)N]-minodronate (1 mg/kg) intravenously and were sacrificed after 3 hr, 24 hr, 1 week, and 1 month. Isotope microscopy showed that [(15)N]-minodronate was present mainly beneath osteoblasts rather than nearby osteoclasts. At 3 hr after minodronate administration, histochemistry and TEM showed osteoclasts with well-developed ruffled borders. However, osteoclasts were roughly attached to the bone surfaces and did not feature ruffled borders at 24 hr after minodronate administration. The numbers of tartrate-resistant acid phosphatase-positive osteoclasts and alkaline phosphatase-reactive osteoblastic area were not reduced suddenly, and apoptotic osteoclasts appeared in 1 week and 1 month after the injections. Von Kossa staining demonstrated that osteoclasts treated with minodronate did not incorporate mineralized bone matrix. Taken together, minodronate accumulates in bone underneath osteoblasts rather than under bone-resorbing osteoclasts; therefore, it is likely that the minodronate-coated bone matrix is resistant to osteoclastic resorption, which results in a long-lasting and bone-preserving effect.


Subject(s)
Bone Density Conservation Agents/analysis , Diphosphonates/analysis , Femur/chemistry , Imidazoles/analysis , Animals , Carbon Isotopes , Cell Count , Femur/cytology , Male , Mice, Inbred ICR , Microscopy/methods , Nitrogen Isotopes , Osteoblasts/cytology , Osteoclasts/cytology
10.
J Nutr Biochem ; 26(7): 696-703, 2015 Jul.
Article in English | MEDLINE | ID: mdl-25792284

ABSTRACT

Mushrooms are the best nonanimal food source of vitamin D2. Pulsed irradiation can enhance vitamin D2 in mushrooms quickly. We investigated the effect of supplementing high vitamin D2Pleurotus ferulae mushrooms in a mouse model of osteoporosis. Thirty-two female C57BL/6JNarl mice were divided into four groups including sham, ovariectomized (OVX), OVX+nonpulsed mushroom (NPM) and OVX+pulsed mushroom (PM). After 23 weeks of treatment, serum samples were analyzed for osteoblast and osteoclast indicators, as well as metabolites using NMR spectroscopy. To examine bone density, femurs were analyzed using micro-computed tomography. The NPM and PM treatment mice showed increased bone density in comparison with OVX mice. In addition, the PM mice showed higher osteoblast and lower osteoclast indicators in comparison with OVX mice. Serum metabolomics analysis indicated several metabolites that were different in PM mice, some of which could be correlated with bone health. Taken together, these results suggest that pulsed irradiated mushrooms are able to increase bone density in osteoporotic mice possibly through enhanced bone metabolism. Further studies in humans are needed to show their efficacy in preventing osteoporosis.


Subject(s)
Bone Density Conservation Agents/therapeutic use , Dietary Supplements , Disease Models, Animal , Ergocalciferols/therapeutic use , Food Irradiation , Osteoporosis, Postmenopausal/prevention & control , Pleurotus/radiation effects , Animals , Biomarkers/blood , Bone Density , Bone Density Conservation Agents/analysis , Bone Density Conservation Agents/radiation effects , Bone and Bones/diagnostic imaging , Crosses, Genetic , Dietary Supplements/analysis , Dietary Supplements/radiation effects , Ergocalciferols/analysis , Female , Food, Preserved/analysis , Food, Preserved/radiation effects , Freeze Drying , Humans , Mice, Inbred C57BL , Mice, Knockout , Nutritive Value/radiation effects , Osteoporosis, Postmenopausal/blood , Osteoporosis, Postmenopausal/diagnostic imaging , Pleurotus/chemistry , Radiography , Random Allocation , Taiwan , Ultraviolet Rays
11.
Bioanalysis ; 6(21): 2931-50, 2014.
Article in English | MEDLINE | ID: mdl-25486238

ABSTRACT

Bisphosphonate drugs pose significant challenges for bioanalysis due to various complicating factors. In 2006, a novel approach, utilizing 'on-column' derivatization with diazomethane, was reported that revolutionized the application of liquid-chromatography-tandem mass spectrometry to bisphosphonates bioanalysis. The methodology enables superior biological sample clean-up while transforming bisphosphonates into species amenable to liquid-chromatography-tandem mass spectrometry detection. Since then, the approach has been successfully applied to numerous bisphosphonates. The use of an alternative methylation reagent - trimethylsilyl diazomethane - for on-column derivatization has been reported recently. This review focuses on published methods utilizing on-column derivatization for bioanalysis of major bisphosphonate drugs in biological matrices. Critical points required for successful application of on-column derivatization to the bioanalysis of bisphosphonates will be discussed.


Subject(s)
Bone Density Conservation Agents/analysis , Chromatography, High Pressure Liquid , Diphosphonates/analysis , Tandem Mass Spectrometry , Bone Density Conservation Agents/blood , Bone Density Conservation Agents/urine , Diphosphonates/blood , Diphosphonates/urine , Humans , Limit of Detection , Solid Phase Extraction
13.
J Chromatogr A ; 1365: 131-9, 2014 Oct 24.
Article in English | MEDLINE | ID: mdl-25242223

ABSTRACT

A simple, sensitive and fast hydrophilic interaction liquid chromatography (HILIC) method using ultraviolet diode-array detector (UV-DAD)/electrospray ionization tandem mass spectrometry was developed for the automated high performance liquid chromatography (HPLC) determination of sodium risedronate (SR) and its degradation products in new pharmaceuticals. The chromatographic separations were performed on Ascentis Express HILIC 2.7µm (150mm×2.1mm, i.d.) stainless steel column (fused core). The mobile phase consisted of formate buffer solution (pH 3.4; 0.03M)/acetonitrile 42:58 and 45:55 (v/v) for granules for oral solution and effervescent tablet analysis, respectively, at a flow-rate of 0.2mL/min, setting the wavelength at 262nm. Stability characteristics of SR were evaluated by performing stress test studies. The main degradation product formed under oxidation conditions corresponding to sodium hydrogen (1-hydroxy-2-(1-oxidopyridin-3-yl)-1-phosphonoethyl)phosphonate was characterized by high performance liquid chromatography-electrospray ionization-mass tandem mass spectrometry (HPLC-ESI-MS/MS). The validation parameters such as linearity, sensitivity, accuracy, precision and selectivity were found to be highly satisfactory. Linear responses were observed in standard and in fortified placebo solutions. Intra-day precision (relative standard deviation, RSD) was ≤1.1% for peak area and ≤0.2% for retention times (tR) without significant differences between intra- and inter-day data. Recovery studies showed good results for all the examined compounds (from 98.7 to 101.0%) with RSD ranging from 0.6 to 0.7%. The limits of detection (LOD) and quantitation (LOQ) were 1 and 3ng/mL, respectively. The high stability of standard and sample solutions at room temperature means an undoubted advantage of the method allowing the simultaneous preparation of many samples and consecutive chromatographic analyses by using an autosampler. The developed stability indicating method is suitable for the quality control of SR in new and commercial pharmaceutical formulations.


Subject(s)
Bone Density Conservation Agents/analysis , Etidronic Acid/analogs & derivatives , Chromatography, High Pressure Liquid/methods , Etidronic Acid/analysis , Hydrophobic and Hydrophilic Interactions , Limit of Detection , Quality Control , Reproducibility of Results , Risedronic Acid , Spectrometry, Mass, Electrospray Ionization/methods , Tablets , Tandem Mass Spectrometry/methods
14.
Article in English | MEDLINE | ID: mdl-23954589

ABSTRACT

An in vitro method for extraction and quantification of zoledronic acid (ZA) from murine bone was developed. Whole mouse bones were incubated in ZA solutions with predetermined concentrations and bound ZA was subsequently extracted from bone with phosphoric acid and derivatized using trimethylsilyl diazomethane (TMS-DAM). ZA tetra-methyl phosphonate was quantified by liquid chromatography coupled with tandem mass spectrometry (LC/MS/MS). This resulted in a sensitive, accurate, and precise method that was linear over three orders of magnitude (0.0250-50.0µg/mL ZA). For quality control (QC) samples, intra-and inter-day coefficients of variance were calculated and were less than 10%. This method was then applied to an in vivo model to quantitate ZA from the femur and mandible of three mice treated with ZA for two weeks. The mean ZA extracted from the mandible was four fold higher than that extracted from the femur (3.06±0.52 vs. 0.76±0.09ng/mg, respectively) indicating that ZA did not distribute equally in the skeleton and had a preference to the mandible. In conclusion, a highly sensitive method to measure ZA from mouse skeleton was developed, which can be easily adapted to multiple mammalian models including humans receiving ZA treatment.


Subject(s)
Chromatography, Liquid/methods , Diphosphonates/analysis , Femur/chemistry , Imidazoles/analysis , Mandible/chemistry , Tandem Mass Spectrometry/methods , Animals , Bone Density Conservation Agents/analysis , Linear Models , Male , Mice , Reproducibility of Results , Sensitivity and Specificity , Zoledronic Acid
15.
Nutr. hosp ; 27(6): 1886-1893, nov.-dic. 2012. ilus, tab
Article in English | IBECS | ID: ibc-112170

ABSTRACT

Background: Several lines of evidence suggest a tight association between oxidative stress and the pathogenesis of osteoporosis in humans. The intake of antioxidants may influence Bone Mineral Density by acting as free radical scavengers, preventing oxidation-induced damage to bone cells. Objective: The aim of this study was to assess the association between the Dietary Antioxidant Quality Score and bone mineral density in a sample of healthy women. Methods: A total of 280 women were grouped into three major groups: women aged ≤ 35 years; women aged 36-45, and finally women aged >45 years. Calcaneous Bone Mineral Density (g/cm2) was measured by dual energy X-ray absorptiometry. Data on the eating habits of each participant were collected with a structured 24-hour diet recall questionnaire. A Dietary Antioxidant Quality Score was used to calculate antioxidant-nutrient intake. Results: A significant and positive association was observed among Bone Mineral Density and dietary intake of vitamin C and selenium. Zinc intake was significantly related to Bone Mineral Density in the youngest group. Low antioxidant consumers were considered individuals whose Dietary Antioxidant Quality Score was lower or equal than the median (3.5), and high antioxidant consumers were those whose Dietary Antioxidant Quality Score were higher than 3.5. Bone Mineral Density was higher in the participants defined as high antioxidant consumers in all aged groups. Conclusion: The study showed that there is an association between Bone Mineral Density and the Dietary Antioxidant Quality Score in all the women studied. Therefore, new therapies for osteoporosis based on higher dietary antioxidant intakes might be developed basing on the results obtained in this study (AU)


Antecedentes: Varias líneas de evidencia sugieren que existe una estrecha relación entre el estrés oxidativo y la patogénesis de la osteoporosis en humanos. La ingesta de nutrientes antioxidantes puede influenciar la densidad mineral ósea al neutralizar los radicales libres, previniendo el daño oxidativo a las células de hueso. Objetivo: El objetivo del presente estudio es establecer la asociación entre un Índice de Calidad Antioxidante de la Dieta y la densidad mineral ósea en una muestra de mujeres sanas. Métodos: Un total de 280 mujeres participaron en el estudio. Las participantes fueron agrupadas por edad en tres categorías: edad ≤ 35 años; edad entre 36 y 45 años y con edad superior a 45 años. Las medidas de la densidad mineral ósea (g/cm2) del calcáneo fueron realizadas por absorciometría dual de rayos X. Los datos sobre los hábitos alimentarios de cada participante fueron recogidos mediante recordatorios de 24 horas. El Índice de Calidad Antioxidante de la Dieta se utilizó para calcular la ingesta total de nutrientes antioxidantes. Resultados: La ingesta de vitamina C y selenio está asociada significativamente a la densidad mineral ósea. En el grupo de mujeres de edad inferior, la ingesta de zinc está relacionada con la masa ósea. Los individuos cuyo Índice de Calidad Antioxidante de la Dieta es inferior o igual a la mediana (3,5) son considerados de bajo consumo antioxidante, y aquellos individuos cuyo Índice de Calidad Antioxidante de la Dieta es superior a 3,5 se consideran de alto consumo antioxidante. En todos los grupos estudiados, la densidad mineral ósea fue significativamente superior en los sujetos cuya dieta tiene un alto consumo de nutrientes antioxidantes. Conclusión: El trabajo muestra que existe una asociación entre la densidad mineral ósea y el Índice de Calidad Antioxidante de la Dieta en todos los grupos de mujeres estudiadas. Por lo tanto, basándose en los resultados de este estudio, se pueden desarrollar nuevas terapias para la osteoporosis basadas en una ingesta elevada de nutrientes antioxidantes (AU)


Subject(s)
Humans , Female , Bone Density , Antioxidants/administration & dosage , Osteoporosis/diet therapy , Bone Density Conservation Agents/analysis , Diet , Feeding Behavior/physiology , Nutrients/analysis
16.
J Sep Sci ; 35(5-6): 681-7, 2012 Mar.
Article in English | MEDLINE | ID: mdl-22271633

ABSTRACT

A simple, rapid and sensitive CE-fluorescence (FL) detection method for the analysis of alendronate (ALEN), a bisphosphonate drug, has been developed. Using a buffer solution of 20 mM sodium phosphate (pH 10.0) and a voltage of 24 kV, separation of ALEN in a 55-cm length (35-cm effective length) capillary was achieved in 5 min. FL detection of ALEN was performed via pre-column derivatization with 2,3-naphthalene dicarbox-yaldehyde (NDA). Linear correlation (r=0.9981, n=6) between FL intensity and analyte concentration was obtained in the range of 7-200 ng/mL ALEN. The developed CE-FL method was applied to the analysis of ALEN in human urine and plasma samples. In order to eliminate the interfering matrix components, SPE using magnetic Fe(3) O(4) @Al(2) O(3) nanoparticles as solid sorbents was employed to clean the biological fluids before CE-FL analysis. The linear ranges of ALEN in urine and plasma were 5-100 ng/mL (r = 0.9982, n = 7) and 5-70 ng/mL (r = 0.9954, n = 7), respectively. The LOD and LOQ in both urine and plasma samples were 1.5 and 5 ng/mL ALEN, respectively. Total analysis time including sample pre-treatment and CE separation was less than 1.5 h.


Subject(s)
Alendronate/analysis , Alendronate/isolation & purification , Bone Density Conservation Agents/analysis , Bone Density Conservation Agents/isolation & purification , Electrophoresis, Capillary/methods , Solid Phase Extraction/methods , Alendronate/blood , Alendronate/urine , Bone Density Conservation Agents/blood , Bone Density Conservation Agents/urine , Electrophoresis, Capillary/instrumentation , Female , Humans , Magnetics , Solid Phase Extraction/instrumentation , Spectrometry, Fluorescence
17.
J Periodontol ; 83(1): 11-8, 2012 Jan.
Article in English | MEDLINE | ID: mdl-21542734

ABSTRACT

BACKGROUND: Alendronate (ALN), an aminobisphosphonate, is known to inhibit osteoclastic bone resorption and was proposed to have osteostimulative properties in vivo and in vitro as shown by an increase in matrix formation. The present study aims to explore the efficacy of a 1% ALN gel compared to a placebo gel as a local drug delivery system in adjunct to scaling and root planing (SRP) for the treatment of intrabony defects in patients with chronic periodontitis. METHODS: A total of 66 intrabony defects were treated with a 1% ALN or placebo gel. The ALN gel was prepared by adding ALN to a polyacrylic acid-distilled water mixture. Clinical parameters (modified sulcus bleeding index, plaque index, probing depth [PD], and clinical attachment level [CAL]) were recorded at baseline and 2 and 6 months, and radiographic parameters at baseline and 6 months. The defect fill at baseline and 6 months was calculated on standardized radiographs by using image-analysis software. RESULTS: The mean PD reduction and CAL gain were greater in the ALN group than in the placebo group at 2 and 6 months. Furthermore, a significantly greater mean percentage of bone fill was found in the ALN group (40.4% ± 11.71%) than in the placebo group (2.5% ± 1.02%). CONCLUSIONS: Results of the present study shows that the local delivery of 1% ALN into the periodontal pocket stimulated a significant increase in PD reduction, CAL gain, and improved bone fill compared to a placebo gel as an adjunct to SRP. These results can provide a new direction in the field of periodontal healing.


Subject(s)
Alendronate/administration & dosage , Alendronate/therapeutic use , Alveolar Bone Loss/drug therapy , Bone Density Conservation Agents/administration & dosage , Bone Density Conservation Agents/therapeutic use , Chronic Periodontitis/drug therapy , Drug Delivery Systems , Adult , Alendronate/analysis , Alveolar Bone Loss/diagnostic imaging , Alveolar Bone Loss/therapy , Bone Density Conservation Agents/analysis , Bone Regeneration/drug effects , Chronic Periodontitis/diagnostic imaging , Chronic Periodontitis/therapy , Dental Scaling , Female , Gels , Gingival Crevicular Fluid/chemistry , Humans , Male , Middle Aged , Periodontal Index , Periodontal Pocket/drug therapy , Periodontal Pocket/therapy , Radiography
18.
Can J Vet Res ; 75(2): 128-33, 2011 Apr.
Article in English | MEDLINE | ID: mdl-21731184

ABSTRACT

This study assessed the feasibility of measuring tiludronate in horses using a minimally invasive bone biopsy technique. Eight horses were treated with intravenous (IV) tiludronate [1 mg/kg bodyweight (BW)], either once (n = 4) or twice, 28 d apart (n = 4). The horses that were treated once were euthanized on days 1, 43, 57, or 92 and those that were treated twice, were euthanized on days 112, 154, 194, or 364. Bone samples were taken bilaterally from each horse at 4 sites: the third metacarpal bone (MCIII), the 13th rib (R13), the tuber coxae (TC), and the cuboid bone (CB). Test samples were taken with a 5-mm diameter dental drill, while larger reference samples were taken with an osteotome. The concentrations of tiludronate were measured by high performance liquid chromatography (HPLC) with ultraviolet (UV) detection. The TC was the easiest site to sample, and no technical difficulties were encountered for extraction and measurement. Drill sampling at the MCIII was difficult. Moreover, both the extraction and measurement caused technical problems and results were unreliable in most cases (93%). Drill samples obtained from the R13 were very small and access to the CB required considerable dissection, which would not be feasible in vivo. Forty-six percent and 36% of the tiludronate measurements performed on the R13 and CB samples, respectively, were unreliable. The ratio of tiludronate concentrations ranged from 73% to 185% (median: 118%) in the TC, 65% to 208% (median: 81%) in the R13, and 26% to 110% (median: 57%) in the CB. In all but 1 horse, the highest concentrations of tiludronate were found in the TC. It was concluded that bone biopsies performed at the TC were adequate for measuring tiludronate in horses and should be considered in future for repeated measurements over time in living animals.


Subject(s)
Biopsy/veterinary , Bone Density Conservation Agents/analysis , Bone and Bones/chemistry , Diphosphonates/analysis , Horses , Animals , Biopsy/methods , Bone Density Conservation Agents/administration & dosage , Bone and Bones/pathology , Diphosphonates/administration & dosage , Drug Administration Schedule/veterinary , Feasibility Studies , Infusions, Intravenous/veterinary , Male , Metacarpal Bones/chemistry , Metacarpal Bones/pathology , Tarsal Bones/chemistry , Tarsal Bones/pathology , Time Factors
19.
J Am Diet Assoc ; 111(5): 687-95, 2011 May.
Article in English | MEDLINE | ID: mdl-21515114

ABSTRACT

BACKGROUND: Adequate lifelong calcium intake is essential in optimizing bone health. Recent National Health and Nutrition Examination Survey data were used to quantify variation in calcium intake across adult age groups and to relate age-associated changes in calcium intake with energy intake. Additional goals were to assess differences in dietary calcium intake between supplemental calcium users and nonusers and to evaluate associations between age and calcium density in the diet. DESIGN: This cross-sectional analysis determined calcium and energy intake for National Health and Nutrition Examination Survey respondents during 2003-2006. Diet was assessed with 24-hour recall and supplement use via questionnaire. Trends in median intakes for dietary calcium, total calcium, and energy across age categories were assessed using survey analysis methods. Nutrient density was represented using calcium to energy intake ratios. RESULTS: The analyses included data from 9,475 adults. When compared to the 19- to 30-year age group, median dietary calcium intake was lower in the ≥81-year age group by 23% in men (P<0.001) and by 14% in women (P=0.003). These reductions coincided with 35% and 28% decreases, respectively, in median energy intake (P<0.001 for each sex). In contrast, the frequency of calcium supplement use increased (P<0.001) with age in both men and women. Yet, among female supplement users, the decline in median dietary calcium intake was greater than in nonusers (P=0.02). Calcium density in the diet significantly increased relative to age in men and women (P<0.001 for each sex); however, dietary and total calcium to energy ratios were insufficient to meet target ratios inferred by adequate intake standards after age 50 years. CONCLUSIONS: Although supplemental calcium use and calcium density were highest in older age groups, they were not sufficient in meeting recommended levels. New approaches to increasing the frequency and level of calcium supplement use to enhance calcium density in diets may be necessary to reduce osteoporosis risk among older Americans.


Subject(s)
Bone Density Conservation Agents/administration & dosage , Calcium, Dietary/administration & dosage , Diet/standards , Energy Intake/physiology , Adult , Age Distribution , Aged , Aged, 80 and over , Bone Density Conservation Agents/analysis , Calcium, Dietary/analysis , Cross-Sectional Studies , Dietary Supplements , Female , Humans , Male , Mental Recall , Middle Aged , Nutrition Surveys , Nutritive Value , Osteoporosis , Surveys and Questionnaires , United States
20.
J Periodontol ; 82(2): 281-6, 2011 Feb.
Article in English | MEDLINE | ID: mdl-20731588

ABSTRACT

BACKGROUND: Bisphosphonate-associated osteonecrosis (BON) of the jaw is a growing concern in the dental community, but the possible presence of residual bisphosphonates in demineralized allograft bone from bisphosphonate-using tissue donors and the clinical implications of using such bone are unclear. The objectives of this study are to determine whether alendronate remained in demineralized bone matrix (DBM) procured from donors with a documented history of oral bisphosphonate use and to examine whether the demineralization process removes alendronate from allograft bone. METHODS: A gas chromatography?mass spectrometry method was developed and validated to quantify residual alendronate in allograft bone. Alendronate levels in DBM procured from tissue donors with a history of oral bisphosphonate use were compared to alendronate levels in DBM procured from donors without a history of bisphosphonate use. In addition, mineralized and demineralized bone was soaked in alendronate at concentrations of 0.002, 2.0, and 2,000 ng/mg bone and analyzed to examine the effect of the demineralization process. RESULTS: Residual alendronate was not detected in the DBM from either group, nor was it detected in any of the DBM samples soaked in alendronate solutions. Soaked mineralized bone contained measureable alendronate, but the substance was removed by demineralization. CONCLUSIONS: The demineralization process effectively removed residual alendronate from allograft bone. These results may relieve anxieties regarding the use of DBM in dental patients because it is unlikely to trigger BON of the jaw.


Subject(s)
Alendronate/analysis , Bone Demineralization Technique , Bone Density Conservation Agents/analysis , Bone Matrix/chemistry , Bone Transplantation/adverse effects , Osteonecrosis/prevention & control , Aged , Alendronate/adverse effects , Bone Demineralization Technique/methods , Bone Density Conservation Agents/adverse effects , Bone Matrix/transplantation , Bone Transplantation/methods , Female , Humans , Male , Middle Aged , Osteonecrosis/chemically induced , Tissue Donors
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