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      The effect of serum magnesium levels and serum Endothelin-1 levels on bone mineral density in protein energy malnutrition Translated title: Efecto de los niveles séricos de magnesio y los niveles séricos de Endotelina-1 sobre la densidad mineral osea en la malnutrición calórico-proteica

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          Abstract

          An inadequate and imbalanced intake of protein and energy results in protein-energy malnutrition (PEM). It is known that bone mineral density and serum magnesium levels are low in malnourished children. However, the roles of serum magnesium and endothelin-1 (ET-1) levels in the pathophysiology of bone mineralization are obscure. Thus, the relationships between serum magnesium and ET-1 levels and the changes in bone mineral density were investigated in this study. There was a total of 32 subjects, 25 of them had PEM and seven were controls. While mean serum ET-1 levels of the children with kwashiorkor and marasmus showed no statistically significant difference, mean serum ET-1 levels of both groups were significantly higher than that of the control group. Serum magnesium levels were lower than normal value in 9 (36%) of 25 malnourished children. Malnourished children included in this study were divided into two subgroups according to their serum magnesium levels. While mean serum ET-1 levels in the group with low magnesium levels were significantly higher than that of the group with normal magnesium levels (p < 0.05), mean bone mineral density and bone mineral content levels were significantly lower (p < 0.05). In conclusion, many factors play a role in the pathophysiology of changes in bone mineral density in malnutrition. Our study suggested that lower magnesium levels and higher ET-1 levels might be important factors in changes of bone mineral density in malnutrition. We recommend that the malnourished patients, especially with hypomagnesaemia, should be treated with magnesium early.

          Translated abstract

          El consumo inadecuado y desbalanceado de proteínas y calorías energía conduce a la malnutrición calórico-proteica (MCP). Se sabe que la densidad mineral ósea y los niveles séricos de magnesio son bajos en los ninos malnutridos. Sin embargo, no está claro el papel que desempenan los niveles séricos de magnesio y los niveles séricos de endotelina-1 (ET-1) en la patofisiología de la mineralización del hueso. Por consiguiente, las relaciones entre los niveles séricos de magnesio y los niveles séricos de ET-1, y los cambios en la densidad mineral ósea, constituyen el objeto de investigación de este estudio. Hubo un total de 32 sujetos; 25 de ellos tenían DCP y 7 eran considerados. Si bien los niveles séricos promedios de ET-1 de los ninos con kwashiorkor y marasmo no mostraron diferencia estadística significativa, los niveles séricos promedio de ET-1 de ambos grupos fueron significativamente más altos que los del grupo de control. Los niveles séricos de magnesio estuvieron por debajo del valor normal en 9 (36%) de 25 ninos malnutridos. Los ninos malnutridos incluidos en este estudio fueron divididos en dos sub-grupos según sus niveles de magnesio en suero. Mientras que los niveles séricos promedio de ET-1 en el grupo con niveles bajos de magnesio fueron significativamente más altos que los del grupo con niveles normales de magnesio (p < 0.05), la densidad mineral ósea promedio y los niveles promedio del contenido mineral óseo fueron significativamente más bajos (p < 0.05). En conclusión, muchos factores juegan un papel en la patofisiología de los cambios en la densidad mineral ósea por la malnutrición. Nuestro estudio sugirió niveles más bajos de magnesio y niveles más altos de ET-1 podrían ser factores importantes en los cambios de densidad mineral ósea en la malnutrición. Se recomienda que los pacientes malnutridos, especialmente a causa de hipomagnesemia, sean tratados con magnesio lo más pronto posible.

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          Most cited references26

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          Nutritional influences on bone mineral density: a cross-sectional study in premenopausal women.

          The association between current and past dietary intake and bone mineral density (BMD) was investigated in 994 healthy premenopausal women aged 45-49 y. BMD was measured with dual-energy X-ray absorptiometry (DXA). Dietary intake was assessed with a food-frequency questionnaire (FFQ). Energy-adjusted nutrient intakes were grouped into quartiles and mean BMD at the lumbar spine (LS), femoral neck (FN), femoral trochanter (FT), and femoral Wards (FW) were calculated. With higher intakes of zinc, magnesium, potassium, and fiber, LS BMD was significantly higher (P < 0.05-0.006), and a significant difference in LS BMD was also found between the lowest and highest quartiles for these nutrients and vitamin C intake (P < 0.05-0.01). These results remained significant after adjustment for important confounding factors. LS BMD and FT BMD were lower in women reporting a low intake of milk and fruit in early adulthood than in women with a medium or high intake (P < 0.01). High, long-term intake of these nutrients may be important to bone health, possibly because of their beneficial effect on acid-base balance.
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            Magnesium-deficiency elevates circulating levels of inflammatory cytokines and endothelin.

            We have developed two rodent models of diet-induced magnesium-deficiency in which histologically defined cardiac lesions can be induced within two to three weeks. During the development of these lesions, the magnesium-deficient animals exhibit circulating cytokine levels which are indicative of a generalized inflammatory state. Dramatic elevations of the macrophage-derived cytokines, IL-1, IL-6, and TNF-alpha together with significantly elevated levels of the endothelial cell-derived cytokine, endothelin, were detected in the plasma of these animals. We believe that the pathophysiological effects caused by the action of these cytokines may play a role in the promotion of cardiovascular pathology associated with magnesium deficiency.
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              Anabolic effects of 1,25-dihydroxyvitamin D3 on osteoblasts are enhanced by vascular endothelial growth factor produced by osteoblasts and by growth factors produced by endothelial cells.

              Human osteoblast-like cells (HOB) produce vascular endothelial growth factor (VEGF), the steady state level of which is stimulated by 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3]. As osteoblasts and endothelial cells are proximally located in skeletal tissue, we investigated the anabolic effects of 1,25-(OH)2D3 and VEGF on HOB cocultured with endothelial cells. When HOB with high alkaline phosphatase (Al-P) activity and human umbilical vein endothelial cells (HUVEC) with little activity were cultured together, Al-P activity increased, accompanied by an increase in cell number. When HOB and HUVEC were cultured separately, 1,25-(OH)2D3 did not directly stimulate [3H]thymidine incorporation into HUVEC, but stimulated it in the presence of HOB. VEGF did not directly stimulate the Al-P activity of HOB but stimulated it in the presence of HUVEC. The conditioned medium of HOB stimulated the proliferation of HUVEC, and this was partially blocked by anti-VEGF antibody. Conversely, the conditioned medium of HUVEC increased Al-P activity and [3H]thymidine incorporation into HOB, and this was partially blocked by antiinsulin-like growth factor I antibody and BQ-123, a specific antagonist of the endothelin-1 (ET-1) receptor. 1,25-(OH)2D3 stimulated the release of VEGF and ET-1 from HOB and HUVEC, respectively. Furthermore, the 1,25-(OH)2D3-induced release of VEGF was enhanced in HOB cocultured with HUVEC. A quantitative reverse transcription-PCR study revealed that genes for VEGF receptors (Flt-1 and KDR) were expressed in HUVEC, but not in HOB, and that 1,25-(OH)2D3 increased the levels of expression of VEGF receptor genes in endothelial cells only when cocultured with HOB. In summary, we demonstrated that 1,25-(OH)2D3 exerts an anabolic effect on osteoblasts by enhancing their production of VEGF, which stimulates its receptors on endothelial cells, followed by increased production of osteotropic growth factors, such as insulin-like growth factor I and ET-1. These in vitro findings suggest that the VEGF/VEGF receptor system may be involved in both bone formation and bone remodeling in vivo.
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                Author and article information

                Contributors
                Role: ND
                Role: ND
                Role: ND
                Role: ND
                Journal
                wimj
                West Indian Medical Journal
                West Indian med. j.
                The University of the West Indies (Mona, , Jamaica )
                0043-3144
                2309-5830
                June 2012
                : 61
                : 3
                : 213-218
                Affiliations
                [02] orgnameDepartment of Paediatric Endocrinology and Metabolism
                [03] Erzurum orgnameAtatürk University orgdiv1Faculty of Medicine orgdiv2Department of Biochemistry Turkey
                [01] orgnameDepartment of Paediatrics
                Article
                S0043-31442012000300002
                e7bbe490-3348-46e7-a4d1-46d8367a6bee

                This work is licensed under a Creative Commons Attribution 4.0 International License.

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                Figures: 0, Tables: 0, Equations: 0, References: 33, Pages: 6
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                SciELO West Indians

                Categories
                Original Articles

                Bone mineral density,endothelin-1,magnesium,protein-energy malnutrition,densidad mineral ósea,endotelina-1,malnutrición calórico-proteica

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