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Magnesium and Osteoporosis: Current State of Knowledge and Future Research Directions


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A tight control of magnesium homeostasis seems to be crucial for bone health. On the basis of experimental and epidemiological studies, both low and high magnesium have harmful effects on the bones. Magnesium deficiency contributes to osteoporosis directly by acting on crystal formation and on bone cells and indirectly by impacting on the secretion and the activity of parathyroid hormone and by promoting low grade inflammation. Less is known about the mechanisms responsible for the mineralization defects observed when magnesium is elevated. Overall, controlling and maintaining magnesium homeostasis represents a helpful intervention to maintain bone integrity.
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Nutrients 2013, 5, 3022-3033; doi:10.3390/nu5083022
ISSN 2072-6643
Magnesium and Osteoporosis: Current State of Knowledge and
Future Research Directions
Sara Castiglioni
, Alessandra Cazzaniga
, Walter Albisetti
and Jeanette A. M. Maier
Department of Biomedical and Clinical Sciences L. Sacco, University of Milan, Via GB Grassi 74,
Milan I-20157, Italy; E-Mails: (S.C.); (A.C.)
Department of Biomedical, Surgical and Dental Sciences, University of Milan, Via Commenda 10,
Milan I-20157, Italy; E-Mail:
* Author to whom correspondence should be addressed; E-Mail:;
Tel.: +39-02-5031-9648; Fax: +39-02-5031-9659.
Received: 18 June 2013; in revised form: 14 July 2013 / Accepted: 22 July 2013 /
Published: 31 July 2013
Abstract: A tight control of magnesium homeostasis seems to be crucial for bone health.
On the basis of experimental and epidemiological studies, both low and high magnesium
have harmful effects on the bones. Magnesium deficiency contributes to osteoporosis
directly by acting on crystal formation and on bone cells and indirectly by impacting on the
secretion and the activity of parathyroid hormone and by promoting low grade
inflammation. Less is known about the mechanisms responsible for the mineralization
defects observed when magnesium is elevated. Overall, controlling and maintaining
magnesium homeostasis represents a helpful intervention to maintain bone integrity.
Keywords: osteoporosis; magnesium; osteoblast; osteoclast
1. Introduction
Osteoporosis is a multifactorial disease characterized by loss of bone mass due to a marked bone
microarchitecture deterioration [1]. Physiologically, bone is constantly remodeled by concerted and
coordinated interactions between osteoclasts, the cells primarily involved in bone resorption, and
osteoblasts, which ensure bone formation and mineralization. Osteoporosis results from an imbalance
between bone deposition and resorption. The consequent decline of bone mass increases the risk of
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fractures, in particular hip and spine fractures, which are associated with substantial pain and suffering,
disability, and even death [1].
Osteoporosis affects millions people worldwide, predominantly postmenopausal women. In the
United States low bone mass is a threat for more than 40 million people [2]. In Europe, the prevalence
of osteoporosis is expected to affect more than 30 million people by the year 2050 [3]. Frequently
associated with aging, osteoporosis is a major health concern since the aging population will double
over the next decade with enormous cost burden on the healthcare systems. Osteoporosis therapies are
available and fall into two classes, anabolic drugs, which induce bone formation, and anti-resorptive
drugs, which retard bone resorption. In addition, modifications of lifestyle, i.e., regular physical activity,
no alcohol, no smoke, balanced diet, are highly recommended in patients with osteoporosis [1]. In
general, because osteoporosis reflects peak bone mass determined by factors preceding skeletal
maturity [4], there is a growing interest in preventive strategies for decreasing the incidence of
osteoporosis in future decades. Dietary interventions are among them. Indeed, nutritional factors are of
particular importance to bone health and they are modifiable by providing food-based
recommendations. A correct diet is particularly important in the young, before skeletal maturity is
reached. While calcium and vitamin D have been the master focus of nutritional prevention of
osteoporosis, several additional food constituentssuch as phytoestrogens, flavonoids, vitamins A, B,
C, E, folateand minerals among which copper, zinc, selenium, iron fluoride and magnesium (Mg),
are known to be important [5]. In particular, a significant association has been found between bone
density and the intake of Mg, an essential micronutrient with a wide range of metabolic, structural and
regulatory functions [6].
2. Magnesium and the Bone: Molecular, Biochemical and Cellular Insights
About 60% of total Mg is stored in the bone. One third of skeletal Mg resides on cortical bone
either on the surface of hydroxyapatite or in the hydration shell around the crystal [7]. It serves as a
reservoir of exchangeable Mg useful to maintain physiological extracellular concentrations of the
cation [6]. Bone surface Mg levels are related to serum Mg. Accordingly, surface bone Mg increases
with Mg loading, as described in chronic renal disease [8]. The larger fraction of bone Mg is probably
deposited as an integral part of the apatite crystal and its release follows the resorption of bone. Apart
from a structural role in the crystals, Mg is essential to all living cells, including osteoblasts and
osteoclasts. Intracellularly, Mg is vital for numerous physiological functions. First of all, Mg is
fundamental for ATP, the main source of energy in the cells. Moreover, Mg is cofactor of hundreds of
enzymes involved in lipid, protein and nucleic acid synthesis. Because of its positive charge, Mg
stabilizes cell membranes. It also antagonizes calcium [9] and functions as a signal transducer [10]. It
is therefore not surprising that alterations of Mg homeostasis impact on cell and tissue functions.
3. Low Magnesium and Osteoporosis: Experimental Evidence
In several studies on different species, dietary Mg restriction promotes osteoporosis [11]. Bones of
Mg deficient animals are brittle and fragile, microfractures of the trabeculae can be detected and
mechanical properties are severely impaired [12]. Consequently, it is not surprising that a Mg deficient
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diet has a negative effect on the peri-implant cortical bone markedly decreasing tibial cortical
thickness [13].
Several direct and indirect mechanisms contribute to the effects of low Mg on bone density
(Figure 1). Mg deficiency rapidly leads to hypomagnesemia, which is in part buffered through the
mobilization of surface Mg from the bone. In addition, the newly formed crystals of apatite are larger
and better structured in Mg deficient animals than controls, and this affects bone stiffness [14]. It
should also be recalled that low Mg intake retards cartilage and bone differentiation as well as matrix
calcification [15]. In experimental Mg deficiency in rodents, decreased bone formation is partly due
to reduced osteoblastic activity [16]. Accordingly, the number of osteoblasts detected by
histomorphometry is reduced [17,18] and the levels of two markers of osteoblastic function, namely
alkaline phosphatase and osteocalcin, are decreased [14]. Moreover, an increase in the number of
osteoclasts has been described [11]. It is noteworthy that these results in vivo have been confirmed by
in vitro studies and some molecular pathways involved have been unraveled. Indeed, low extracellular
Mg inhibits osteoblast growth by increasing the release of nitric oxide through the upregulation of
inducible nitric oxide synthase [19], while it increases the number of osteoclasts generated from bone
marrow precursors [20].
Figure 1. Present knowledge about the mechanisms involved in linking Mg deficiency and
osteoporosis. Remarkably, similar events are implicated in experimental models and in
humans. Because the vasculature plays an important role in bone remodeling, we also
hypothesize that low Mg induced-endothelial dysfunction contributes to the decline of
bone mass.
Apart from direct effects on the structure and the cells of the skeleton, Mg deficiency impacts on the
bone also indirectly by affecting the homeostasis of the two master regulators of calcium homeostasis,
i.e., parathyroid hormone (PTH) and 1,25(OH)
-vitamin D thus leading to hypocalcemia. In most
species, hypomagnesemia impairs secretion of PTH and renders target organs refractory to PTH.
Because PTH signaling implies the increase of cyclic AMP through the activation of adenylate cyclase,
which requires Mg as a cofactor, resistance to PTH might be due, in part, to the decreased activity of
this enzyme [21]. Reduced secretion of PTH or impaired peripheral response to the hormone lead to
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low serum concentrations of 1,25(OH)
-vitamin D [11,18]. To this purpose it is noteworthy that
25-hydroxycholecalciferol-1-hydroxylase requires Mg [22] and consequently Mg deficiency reduces
the activity of the enzyme.
Hypomagnesemia also promotes inflammation [23] and a relation exists between inflammation and
bone loss [24]. In Mg deficient rodents, TNFα, IL-1s and IL-6 are increased both in serum and in the
bone marrow microenvironment [23]. These cytokines not only amplify osteoclast while inhibiting
osteoblast function but also perpetuate inflammation. Besides, substance P is released at high levels in
Mg deficiency [18]. In addition to enhancing pro-inflammatory cytokine secretion, substance P
released on nerve ending in bone stimulates the activity of the osteoclasts [18].
It is also relevant that Mg restriction promotes oxidative stress, partly as a consequence of
inflammation partly because of the reduced anti-oxidant defenses which occur upon Mg
restriction [25]. The increased amounts of free radicals potentiate the activity of osteoclasts and
depress that of osteoblasts [26].
A last issue that is overlooked in experimental models is about the vasculature in the bone of Mg
deficient animals. An adequate blood supply is necessary for bone health. Interestingly, decreased
intraosseous blood vessel volume and number seems to be relevant in the development of
post-nerve-injury osteoporosis [27] and in old-age associated osteoporosis [28]. Overall, all
experimental data from animal studies indicate that reduced dietary intake of Mg is a risk factor for
osteoporosis through a constellation of different mechanisms.
4. Low Magnesium and Osteoporosis: Studies in Humans
Nutritional monitoring programs have shown an inadequate dietary Mg intake in Europe and North
America [29] which leads to subclinical Mg deficiency. This is mainly due to the features of the
western diet, rich in processed foods and relatively poor in micronutrients. How can Mg intake be
optimized? Since the center of chlorophyll contains Mg, green vegetables are excellent sources of the
metal. Also, nuts, seeds, unprocessed grains and some legumes contain large amounts of Mg.
However, diet is not the only determinant. For a long time, the existence of differences in Mg handling
on a genetic basis has been suspected. Only recently some light has been shed on this issue. In the last
decade, rare cases of hypomagnesemia have been linked to hereditary single-gene mutations [30]
(Table 1). These uncommon disorders lead to the identification and characterization of some molecular
players in Mg homeostasis. These findings fostered studies on the genome and, by single nucleotide
polymorphisms, six different genomic regions were individuated that contain variants reproducibly
associated with low serum Mg levels [31]. Interestingly, only one of the loci described, namely TRPM6,
had a known role in influencing Mg concentrations in humans [32]. These results open new perspectives
in our understanding of the complex mechanisms involved in regulating Mg absorption and distribution
and should be taken into account when the outcomes of interventional studies are evaluated.
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Table 1. Inherited disorders leading to hypomagnesemia. The function of the wild type
protein is briefly described.
* Omim
recessive familial
hypomagnesemia with
hypercalciuria and
Claudin-16 and Claudin-19
Function: tight junction proteins
Localization: thick ascending limb of Henle’s loop and
convolute distal tubule in the kidney
Involved in paracellular epithelial transport
hypomagnesemia with
Function: cation channel and α-kinase
Localization: intestine and distal convolute tubule in the kidney
Involved in transcellular Mg reabsorption in epithelial cells
dominant renal
Function: γ-subunit of the Na
Localization: basolateral membrane of proximal and distal
tubules in the kidney
Involved in transcellular Mg reabsorption
recessive renal
Function: growth factor and magnesiotropic hormone
Involved in stimulating magnesium reabsorption in the renal
distal convoluted tubule via activation of TRPM6
Function: metal trasporter
Localization: ubiquitous; thick ascending limb of Henle’s loop
and basolateral membrane of distal tubule in the kidney
Involved in renal Mg reabsorption
autosomal dominant
myokymia with
Function: voltage-gated K
Localization: ubiquitous; distal convolute tubule in the kidney
Involved in renal Mg reabsorption
* Omim: Online Mendelian Inheritance in Man.
Because Mg homeostasis is regulated through a complex network of transporters in the intestine
and in the kidney, it is not surprising that Mg deficiency is associated with chronic gastrointestinal and
renal diseases [32]. It also complicates diabetes mellitus, sickle cell anemia, therapies with some
classes of diuretics, antibiotics or anti-neoplastic drugs [33,34]. In addition, it is very common in the
elderly and in alcoholists. Some of these conditions share elevated C-reactive protein, a marker of
systemic inflammation, as a common denominator and an inverse correlation exists between Mg intake
and C-reactive protein [35].
Nutrients 2013, 5 3027
Also in humans Mg deficiency contributes to osteoporosis. Low serum Mg is a co-contributing
factor to osteopenia in adults with sickle cell anemia [36]. Moreover, an association between serum
Mg and bone density has been reported in pre and post menopausal women [4,37]. Mg intake was
positively associated with bone mass density in surviving members of the Framingham study [38]. The
same result was obtained in white but not in black males and females (age 7079), thereby raising the
possibility of racial differences in Mg handling [39] which might be explained in the light of the
aforementioned genetic variants of genes implicated in Mg homeostasis [31]. In agreement with the
aforementioned results, Mg supplementation is beneficial in osteoporotic women [40,41].
Building healthy bone throughout life is a strategy to prevent osteoporosis. To this purpose it is
interesting to note that pre-adolescent dietary intake of Mg positively relates to bone mass density in
young adulthood as detected by quantitative ultrasound determination of the calcaneus [42] and that
Mg supplementation for 12 months has a positive effect on the accrual of bone mass in the hip of
peripuberal Caucasian girls [43]. Mg supplementation is therefore important in the periadolescent group,
given the suboptimal dietary Mg intake documented in food surveys in western countries. It is also
interesting that Mg intake is an independent predictor of bone density in young elite swimmers [44].
The mechanisms explaining the effects of Mg deficiency on the bone in humans are similar to what
has been described in experimental models:
(i) low Mg can directly affect the bone by altering the structure of apatite crystals and by acting on
bone cells. Indeed, osteoporotic women with demonstrated Mg deficiency have larger and better
organized crystals in trabecular bone than controls, while in women undergoing hormone replacement
therapy bone Mg is increased and associates with low cristallinity index [45]. We here recall that when
crystals are large bones do not bear a normal load.
(ii) Mg deficiency associates with the reduction of the levels of PTH, the induction of end-organ
resistance to PTH and the decrease of vitamin D [11,46]. Interestingly, many osteoporotic
post-menopausal women who are vitamin D deficient and have low PTH levels are also Mg deficient
and Mg supplementation corrects these biochemical abnormalities [47]. Moreover hypomagnesemic
diabetic children normalize their levels of 1,25(OH)
-vitamin D upon supplementation with Mg [48].
(iii) Mg deficiency associates with low grade inflammation [4,34] and, as mentioned above,
inflammatory cytokines stimulate bone remodelling and osteopenia [23].
(iv) Mg deficiency promotes endothelial dysfunction [49] and it is known that endothelial health is
important for bone health [50]. On these bases, it is tempting to speculate about the possibility that
osteoporosis might be considered a vascular disease of the bone.
(v) Another aspect to consider is the evidence that adults on a western diet develop a low-grade
acidosis which is intensified by aging. Recently, the acid load imposed by this diet has been suggested
to play a role in the pathophysiology of osteoporosis. Indeed, metabolic acidosis has been shown to
lead to calcium loss from bone, to inhibit osteoblast function and stimulate osteoclast activity, and to
impair bone mineralization [51]. Accordingly, a neutralizing diet improves bone micro-architecture
and bone mineral density [52]. It is therefore feasible that part of the effects of Mg on the skeleton is
due to its capability to act as a buffer for the acid produced by the typical western diet [53].
In spite of the evidence showing that Mg is beneficial for the skeleton, warning results were
reported in the Women’s Health Initiative Study where it is shown that postmenopausal women with
the highest quintile of Mg intake have the highest incidence of wrist fracture [5]. These results are in
Nutrients 2013, 5 3028
keeping with some data showing that elevated Mg might have harmful effects on osseous metabolism
and parathyroid gland function, leading to mineralization defects. Indeed, high bone Mg inhibits the
formation of hydroxyapatite crystals by competing with calcium and by binding to pyrophosphate
forming an insoluble salt, not degraded by the enzymes [54]. These events contribute also to
osteomalacic renal osteodystrophy and adynamic bone disease [54]. In patients with chronic renal
failure or in individuals undergoing dialysis, serum Mg concentrations are frequently elevated and
correlate with mineralization defects [54]. Additional intriguing studies were performed on premature
infants with osteopenia secondary to MgSO
maternal administration for preterm labor [55,56]. Since
Mg is a calcium antagonist [9], it is feasible to propose that high concentrations of Mg alter
calcium/Mg ratio, thus leading to dysregulated cell functions. Accordingly, an in vitro inhibitory effect
of high Mg on osteoblast differentiation and mineralizing activity has been shown [57].
Overall, an optimal range of Mg concentrations might be required to ensure bone homeostasis.
More studies are required in vitro and in vivo about the effects of high Mg concentrations on bone
metabolism and structure not only to provide correct nutritional guidelines but also because of the use
of Mg as an orthopedic implant material.
5. Critical Issues and Future Perspective
Mg has been defined the forgotten electrolyte. Indeed, while a lot of literature is available on
calcium, not as much is known about Mg in biomedicine and, specifically, in bone homeostasis. In
addition, the measurement of serum Mg is seldom requested in spite of the evidence that
hypomagnesemia is very common in industrialized countries. Because Mg (i) interferes with
calciotropic hormones and (ii) has been proposed as a natural calcium antagonist, an evaluation of
Mg/calcium balance seems to be pivotal in general, and in particular in the case of bone physiology
and pathology. To our knowledge, there is only one study showing that the ratio of serum and hair
calcium to Mg is a significant indicator of bone mass density [58]. Recent advancement in our
knowledge of bone physiology has shown the complexity of the network of molecules involved in
maintaining skeletal health. The canonical Wnt pathway is emerging as fundamental for the
maintenance of bone homeostasis [59]. Briefly, Wnts are essential in determining the fate of
mesenchymal precursors and in regulating osteoblast proliferation, apoptosis, differentiation and
function [59]. Accordingly, Wnt antagonist sclerostin is involved in osteoporosis and inflammatory
bone loss [60]. No data are available at the moment on this pathway in Mg deficiency. Another hot
area of research relates to the use of mesenchymal stem cells (MSC) for regenerative medicine in
different fields including orthopaedic surgery. To our knowledge nothing is known about the effects of
different concentrations of Mg on MSC survival, growth and differentiation both in vivo and in vitro,
apart from the studies performed with MSC on biodegradable Mg alloys [61]. Also osteocytes have not
been studied in relation to Mg. Far from being passive by-standers in the bone, the osteocytes are
emerging as mechanotransducers and orchestrators of bone remodelling [62]. Many other challenging
questions about Mg and the bone are still unanswered.
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6. Conclusions
Although the evidence is still fragmentary, most of the experimental and clinical data available in
the literature point to Mg as a contributor factor to bone health. Consequently, optimizing Mg intake
might represent an effective and low-cost preventive measure against osteoporosis in individuals with
documented Mg deficiency, while doubts remain about supplementing the general population with the
mineral since too much Mg seems to have detrimental effects on the bone [5,57].
Conflict of Interest
The authors declare no conflict of interest.
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... Magnesium (Mg), the second most abundant intracellular cation, stabilizes DNA and RNA structures and cell membranes and plays an essential role in maintaining the function of many enzymes as co-factors [76,188]. In skeletal bone, Mg deficiency contributes to impaired bone growth, disrupted mineral metabolism, decreased osteoblast, increased osteoclast cell number, and osteoporosis in young animals, with promoted inflammation [105][106][107][108][109]. Mg 2+ is found to enhance the expression of the osteogenesis-related genes, production of extracellular matrix, and deposition of apatite crystal in undifferentiated MSCs and osteoblastic MSCs in vitro, possibly through the upregulation of hypoxia-inducible factor (HIF) and peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1α), respectively [110][111][112]. ...
... In vivo studies also showed enhanced bone regeneration with overexpressed osteogenic markers, OCN, Runx2, and IGF-I, around the implant in vivo [110][111][112]. Nevertheless, Mg 2+ (up to 5 mM) competes with Ca 2+ as an antagonist and forms an insoluble salt with pyrophosphate, causing mineralization defect and cell dysfunction [108,113,114]. ...
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Bone is capable of adjusting size, shape, and quality to maintain its strength, toughness, and stiffness and to meet different needs of the body through continuous remodeling. The balance of bone homeostasis is orchestrated by interactions among different types of cells (mainly osteoblasts and osteoclasts), extracellular matrix, the surrounding biological milieus, and waste products from cell metabolisms. Inorganic ions liberated into the localized microenvironment during bone matrix degradation not only form apatite crystals as components or enter blood circulation to meet other bodily needs but also alter cellular activities as molecular modulators. The osteoinductive potential of inorganic motifs of bone has been gradually understood since the last century. Still, few have considered the naturally generated ionic microenvironment’s biological roles in bone remodeling. It is believed that a better understanding of the naturally balanced ionic microenvironment during bone remodeling can facilitate future biomaterial design for bone tissue engineering in terms of the modulatory roles of the ionic environment in the regenerative process.
... Several direct and indirect mechanisms contribute to the effects of low magnesium on bone density: Low magnesium can directly affect the bone by altering the structure of apatite crystals; magnesium deficiency is also associated with reduction of PTH and 1,25(OH2) D levels and low-grade inflammation and endothelial dysfunction, with a wellknown relation between inflammation and bone loss [16,33]. ...
In this first chapter, we describe different Osteopathies of degenerative or inflammatory nature related to the ageing of people. We are going to give a brief description of the pathogenic processes responsible for bone diseases, with a particular focus on osteoporosis and we will present various options and proposals for the prevention and treatment of changes in bone metabolism with medicines and food supplements. We are going to devote particular attention to the effects of Silicon in these pathologies, until now poorly considered, and we will propose our own formulation composed of Organic Silicon plus trace elements. We have treated a large number of patients, osteopenics or osteoporotics and we have obtained good and encouraging results with this innovative formulation. We therefore consider the proposal presented here to be a valid alternative to traditional pharmacological treatment, with respect to which it has the double advantage of equal effectiveness and absolute absence of side effects.
... Таким образом, можно сказать, что исход беременности в группе «Фактор I «-1» не благоприятен, и это связано с повышенным содержанием таких элементов, как магний и медь у матери и ребенка, что вызывает отравление этими металлами. Данное утверждение основывается на исследованиях, в которых приводится основной диапазон физиологической нормы магния в сыворотке крови -около 0,76-1,15 ммоль/л (18,5-28,0 мг/л) (Swaminathan, 2003;Castiglioni et al., 2013). Причем в норме происходит резкая стимуляция экскреции магния при концентрации магния в сыворотке выше 0,8 ммоль/л (19,4 мг/л) для предотвращения отравления. ...
Цель исследования – выделение из группы элементов (медь, хром, марганец, селен, магний, цинк, стронций) тех, концентрация которых в компонентах крови (плазме и эритроцитах) может быть использована в качестве маркеров для прогнозирования патологии новорожденных. Материалы и методы. Под наблюдением находились 98 пар доношенных новорожденных и их матерей, из них 58 пар из отделения патологии и 40 условно здоровых пар (контрольная группа сравнения). Концентрацию химических элементов проводили методом масс-спектрометрии с индуктивно связанной аргоновой плазмой. Выполнены статистическая обработка, факторный и компонентный анализ полученных количественных значений концентраций элементов в плазме и эритроцитах периферической крови. Результаты. Выявлены группы с экстремальными значениями фактора. Для каждой из групп определены средние показатели анамнестических данных рожениц и данных клинического статуса новорожденных раннего неонатального периода. Для группы «Фактор I «−1» концентрации элементов магний и медь в крови у матери и новорожденного отмечались значительно больше физиологической нормы, что приводит к уменьшению срока гестации и массы новорожденного, увеличению степени задержки внутриутробного развития. В случае группы «Фактор II «+1», концентрации марганца и хрома оказались больше физиологической нормы, в результате чего возрастает вероятность возникновения у новорожденных патологии «Синдром вегето-висцеральных нарушений». Выводы. В качестве маркера перечисленных патологий возможно использовать совместное превышение физиологической нормы концентрации пар элементов магний/медь и марганец/хром в компонентах крови беременных.
... Nevertheless, the quantity is around 2 wt% in the bone tissue and cartilage throughout the commencement of the osteogenesis but tends to diminish in the mature tissues [38]. It has been reported that osteoporosis is straightforwardly related to Mg deficiency, inhibition of skeletal metabolism stages, inhibition of osteoblastic and osteoclastic processes, bone growth, osteopenia and enhanced bone brittleness [217]. ...
... Our study showed that dietary rye inclusion has no effect on the mineral composition of the bone from hens at the end of the laying period, while enzyme supplementation positively influenced not only Ca content, crucial for eggshell formation, but also the content of numerous key microminerals. Bones are the main reservoir of Mg, which is a cofactor for numerous enzymes and in bones it also plays a role in hydroxyapatite crystal formation, preventing osteoporosis [58]. Mn stimulates the synthesis of the bone matrix and improves bone regeneration [59]. ...
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The objective of this study was to evaluate whether there are negative effects of the partial replacement of white corn with rye along with xylanase supplementation on overall bone quality, eggshell mineralization, and mechanical strength in laying hens. From the 26th week of life, ISA Brown laying hens were fed either a wheat–corn diet or a diet containing 25% rye, with or without xylanase. The experimental period lasted for 25 weeks, until birds reached their 50th week of age, after which bone and eggshell quality indices were assessed. Eggshell thickness and eggshell Ca content of eggs from rye-fed hens were improved by xylanase supplementation. No differences in the mechanical properties of the eggshells were observed between treatments, except for the diet-dependent changes in egg deformation. Rye inclusion had no effect on the mechanical properties of bone. Xylanase supplementation, irrespective of the diet, had a positive effect on bone strength and increased tibia Ca content, as well as the content of several microelements. Hence, hybrid rye combined with wheat can replace 25% of corn in layer diets without compromising shell quality or bone mineral content. Xylanase supplementation in these diets is recommended since its inclusion improves both bone strength and quality.
... BGs containing magnesium have the potential to generate a framework that is conducive to the proliferation and activity of human osteoblast-like cells (Balamurugan et al. 2007). Magnesium is a co-factor in a variety of enzymes that are connected to healthy bones and teeth, but it can also inhibit the formation of apatite crystals (Castiglioni et al. 2013). In addition, many Bioverit glass-ceramics, the bioavailability of which has been demonstrated in clinical tests, include substantial quantities of magnesium oxide (Höland et al. 1991). ...
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The introduction of bioactive glasses (BGs) precipitated a paradigm shift in the medical industry and opened the path for the development of contemporary regenerative medicine driven by biomaterials. This composition can bond to live bone and can induce osteogenesis by the release of physiologically active ions. 45S5 BG products have been transplanted effectively into millions of patients around the world, primarily to repair bone and dental defects. Over the years, many other BG compositions have been introduced as innovative biomaterials for repairing soft tissue and delivering drugs. When research first started, many of the accomplishments that have been made today were unimaginable. It appears that the true capacity of BGs has not yet been realized. Because of this, research involving BGs is extremely fascinating. However, to be successful, it requires interdisciplinary cooperation between physicians, glass chemists, and bioengineers. The present paper gives a picture of the existing clinical uses of BGs and illustrates key difficulties deserving to be faced in the future. The challenges range from the potential for BGs to be used in a wide variety of applications. We have high hopes that this paper will be of use to both novice researchers, who are just beginning their journey into the world of BGs, as well as seasoned scientists, in that it will promote conversation regarding potential additional investigation and lead to the discovery of innovative medical applications for BGs.
... Magnesium deficiency adversely affects all metabolic stages of skeleton formation, inhibits bone growth, reduces the activity of osteoblastic and osteoclastic cells, and promotes bone fragility [4]. Moreover, magnesium deficiency influences osteoporosis because it promotes the production of hydroxyapatite, as well as the secretion and activity of parathyroid hormone [5]. On the other hand, an insignificant role of magnesium on mesenchymal stem cells (MSC) differentiation to the osteogenic line was found in Mg-Ca alloy extracts with a higher concentration of ions than in pure Mg alloy, but the synergistic effect of both elements on cell activity was showed [6]. ...
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The effect of nanosilica on the microstructure setting process of tetracalcium phosphate/nanomonetite calcium phosphate cement mixture (CPC) with the addition of 5 wt% of magnesium pyrophosphate (assigned as CT5MP) and osteogenic differentiation of mesenchymal stem cells cultured in cement extracts were studied. A more compact microstructure was observed in CT5MP cement with 0.5 wt% addition of nanosilica (CT5MP1Si) due to the synergistic effect of Mg2P2O7 particles, which strengthened the cement matrix and nanosilica, which supported gradual growth and recrystallization of HAP particles to form compact agglomerates. The addition of 0.5 wt% of nanosilica to CT5MP cement caused an increase in CS from 18 to 24 MPa while the setting time increased almost twofold. It was verified that adding nanosilica to CPC cement, even in a low amount (0.5 and 1 wt% of nanosilica), positively affected the injectability of cement pastes and differentiation of cells with upregulation of osteogenic markers in cells cultured in cement extracts. Results revealed appropriate properties of these types of cement for filling bone defects.
Ukraine chose the path of European integration and became a candidate for membership of the European Union. This made it necessary to adjust the national economy and social sphere to the European standards. The financial market is an active participant in European integration processes, especially during the period of reboot of the national economy. First of all, the subjects of the financial market are the state, business, citizens, that all are economic agents who enter into financial relations as regulators or objects of regulation, investors or consumers of investment resources. The war unleashed by Russian Federation in Ukraine leads to significant destruction in all sectors of the national economy. Reconstruction will require significant financial resources, which will be attracted from various sources. At the same time, the financial market of Ukraine will certainly become one of the most important elements of the reconstruction of the national economy, business and social sector. Ukrainian citizens will also be involved in investment processes, but for this they should know the basics of investment mathematics, financial technologies, and financial literacy. In addition, financial institutions are reluctant to invest in the agricultural and industrial sectors of the economy. The cost of credit resources is too high, and the level of business profitability does not pay off the resources involved. In this context, the subjects of the financial services market, in particular banks and insurance companies, should introduce the principles of social responsibility of financial business to society in corporate governance. Very important issues of today, which are highlighted in the monograph, are the restoration of budgetary stability and debt security of Ukraine in the post-war period, improvement of monetary and budgetary policy aimed at macroeconomic stabilization in the country. The authors emphasize the tools that can ensure anti-crisis regulation of the banking system, financial business management, since banks play an important role in the activation of investment processes during the reconstruction period. In addition, it is necessary to develop business in the production sector of the economy. The monograph examines the issues of ensuring the economic security of the construction industry, directions for improving the accounting policy in the field of business as a whole, and improving the quality of audits. This should ensure quick adaptation of Ukrainian business to international accounting and certification standards. These and other aspects of the current problems and priority directions of the development of the financial market are devoted to the monograph of the team of authors who carry out up to date researches within the scientific school of the National University "Yuri Kondratyuk Poltava Polytechnic". The founder of this school is the rector of the university, doctor of economic sciences, professor, honored worker of education of Ukraine - Volodymyr Onyshchenko. The author's team is grateful to Volodymyr Onyshchenko, who is a scientific director and consultant for most of the participants of this publication. He formed an active position, perseverance and purposefulness in the scientists when choosing topical issues and qualitatively performing of scientific researches. The materials of the monograph are presented in the author's edition, which reflects the position of the authors regarding the outline of the problem and the determination of ways to solve it. The team of authors expresses their gratitude to the reviewers of the monograph manuscript for their wishes, as well as to the foreign partners of the Department of Finance, Banking and Taxation, who contributed to its publication.
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Inflammation is a common albeit overlooked cause of local and systemic bone loss which results from an imbalance between bone formation and bone resorption. The Wnt pathway, which plays an essential role in the regulation of bone turnover, has been proposed as a potential molecular link between inflammation and inflammatory bone loss. We here recapitulate present knowledge about sclerostin, a Wnt pathway inhibitor, and bone damage in inflammation. A better understanding of sclerostin action and regulation might help in designing an effective treatment strategy in inflammatory bone loss.
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Although the following text will focus on magnesium in disease, its role in healthy subjects during physical exercise when used as a supplement to enhance performance is also noteworthy. Low serum magnesium levels are associated with metabolic syndrome, Type 2 diabetes mellitus (T2DM) and hypertension; consequently, some individuals benefit from magnesium supplementation: increasing magnesium consumption appears to prevent high blood pressure, and higher serum magnesium levels are associated with a lower risk of developing a metabolic syndrome. There are, however, conflicting study results regarding magnesium administration with myocardial infarction with and without reperfusion therapy. There was a long controversy as to whether or not magnesium should be given as a first-line medication. As the most recent trials have not shown any difference in outcome, intravenous magnesium cannot be recommended in patients with myocardial infarction today. However, magnesium has its indication in patients with torsade de pointes and has been given successfully to patients with digoxin-induced arrhythmia or life-threatening ventricular arrhythmias. Magnesium sulphate as an intravenous infusion also has an important established therapeutic role in pregnant women with pre-eclampsia as it decreases the risk of eclamptic seizures by half compared with placebo.
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The kidney has a vital role in magnesium homeostasis and, although the renal handling of magnesium is highly adaptable, this ability deteriorates when renal function declines significantly. In moderate chronic kidney disease (CKD), increases in the fractional excretion of magnesium largely compensate for the loss of glomerular filtration rate to maintain normal serum magnesium levels. However, in more advanced CKD (as creatinine clearance falls <30 mL/min), this compensatory mechanism becomes inadequate such that overt hypermagnesaemia develops frequently in patients with creatinine clearances <10 mL/min. Dietary calcium and magnesium may affect the intestinal uptake of each other, though results are conflicting, and likewise the role of vitamin D on intestinal magnesium absorption is somewhat uncertain. In patients undergoing dialysis, the effect of various magnesium and calcium dialysate concentrations has been investigated in haemodialysis (HD) and peritoneal dialysis (PD). Results generally show that dialysate magnesium, at 0.75 mmol/L, is likely to cause mild hypermagnesaemia, results for a magnesium dialysate concentration of 0.5 mmol/L were less consistent, whereas serum magnesium levels were mostly normal to hypomagnesaemic when 0.2 and 0.25 mmol/L were used. While dialysate magnesium concentration is a major determinant of HD or PD patients' magnesium balance, other factors such as nutrition and medications (e.g. laxatives or antacids) also play an important role. Also examined in this review is the role of magnesium on parathyroid hormone (PTH) levels in dialysis patients. Although various studies have shown that patients with higher serum magnesium tend to have lower PTH levels, many of these suffer from methodological limitations. Finally, we examine the complex and often conflicting results concerning the interplay between magnesium and bone in uraemic patients. Although the exact role of magnesium in bone metabolism is unclear, it may have both positive and negative effects, and it is uncertain what the optimal magnesium levels are in uraemic patients.
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Magnesium, potassium, and sodium, cations commonly measured in serum, are involved in many physiological processes including energy metabolism, nerve and muscle function, signal transduction, and fluid and blood pressure regulation. To evaluate the contribution of common genetic variation to normal physiologic variation in serum concentrations of these cations, we conducted genome-wide association studies of serum magnesium, potassium, and sodium concentrations using ~2.5 million genotyped and imputed common single nucleotide polymorphisms (SNPs) in 15,366 participants of European descent from the international CHARGE Consortium. Study-specific results were combined using fixed-effects inverse-variance weighted meta-analysis. SNPs demonstrating genome-wide significant (p
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Efforts have been made recently to implement nanoscale surface features on magnesium, a biodegradable metal, to increase bone formation. Compared with normal magnesium, nanostructured magnesium has unique characteristics, including increased grain boundary properties, surface to volume ratio, surface roughness, and surface energy, which may influence the initial adsorption of proteins known to promote the function of osteoblasts (bone-forming cells). Previous studies have shown that one way to increase nanosurface roughness on magnesium is to soak the metal in NaOH. However, it has not been determined if degradation of magnesium is altered by creating nanoscale features on its surface to influence osteoblast density. The aim of the present in vitro study was to determine the influence of degradation of nanostructured magnesium, created by soaking in NaOH, on osteoblast density. Our results showed a less detrimental effect of magnesium degradation on osteoblast density when magnesium was treated with NaOH to create nanoscale surface features. The detrimental degradation products of magnesium are of significant concern when considering use of magnesium as an orthopedic implant material, and this study identified a surface treatment, ie, soaking in NaOH to create nanoscale features for magnesium that can improve its use in numerous orthopedic applications.
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Magnesium (Mg) deficiency has been associated with bone disorders. Physical activity is also crucial for bone mineralization. Bone mass loss has been observed to be accelerated in subjects with low Mg intake. We aim to understand if Mg intake mediates the association between bone mineral density (BMD) and lean soft tissue (LST) in elite swimmers. Seventeen elite swimmers (eight males; nine females) were evaluated. Bone mineral content, BMD, LST, and fat mass were assessed using dual energy X-ray absorptiometry. Energy and nutrient intake were assessed during a seven-day period and analyzed with Food Processor SQL. Males presented lower values than the normative data for BMD. Mg, phosphorus (P) and vitamin D intake were significantly lower than the recommended daily allowance. A linear regression model demonstrated a significant association between LST and BMD. When Mg intake was included, we observed that this was a significant, independent predictor of BMD, with a significant increase of 24% in the R(2) of the initial predictive model. When adjusted for energy, vitamin D, calcium, and P intake, Mg remained a significant predictor of BMD. In conclusion, young athletes engaged in low impact sports, should pay special attention to Mg intake, given its potential role in bone mineral mass acquisition during growth.
Magnesium (Mg(2+)) deficiency is a frequently occurring disorder that leads to loss of bone mass, abnormal bone growth and skeletal weakness. It is not clear whether Mg(2+) deficiency affects the formation and/or activity of osteoclasts. We evaluated the effect of Mg(2+) restriction on these parameters. Bone marrow cells from long bone and jaw of mice were seeded on plastic and on bone in medium containing different concentrations of Mg(2+) (0.8 mM which is 100% of the normal value, 0.4, 0.08 and 0 mM). The effect of Mg(2+) deficiency was evaluated on osteoclast precursors for their viability after 3 days and proliferation rate after 3 and 6 days, as was mRNA expression of osteoclastogenesis-related genes and Mg(2+)-related genes. After 6 days of incubation, the number of tartrate resistant acid phosphatase-positive (TRACP(+)) multinucleated cells was determined, and the TRACP activity of the medium was measured. Osteoclastic activity was assessed at 8 days by resorption pit analysis. Mg(2+) deficiency resulted in increased numbers of osteoclast-like cells, a phenomenon found for both types of marrow. Mg(2+) deficiency had no effect on cell viability and proliferation. Increased osteoclastogenesis due to Mg(2+) deficiency was reflected in higher expression of osteoclast-related genes. However, resorption per osteoclast and TRACP activity were lower in the absence of Mg(2+). In conclusion, Mg(2+) deficiency augmented osteoclastogenesis but appeared to inhibit the activity of these cells. Together, our in vitro data suggest that altered osteoclast numbers and activity may contribute to the skeletal phenotype as seen in Mg(2+) deficient patients.
Context: The acid load imposed by a modern diet may play an important role in the pathophysiology of osteoporosis. Objective: Our objective was to evaluate the skeletal efficacy and safety and the effect on fracture prediction of K-citrate to neutralize diet-induced acid loads. Design and setting: We conducted a randomized, double-blind, placebo-controlled trial at a teaching hospital. Subjects: Subjects included 201 elderly (>65 yr old) healthy men and women (t-score of -0.6 at lumbar spine). Intervention: Intervention was 60 mEq of K-citrate daily or placebo by mouth. All subjects received calcium and vitamin D. Outcome measures: The primary outcome was change in areal bone mineral density (aBMD) at the lumbar spine by dual-energy x-ray absorptiometry after 24 months. Secondary endpoints included changes in volumetric density and microarchitectural parameters by high-resolution peripheral quantitative computed tomography in both radii and both tibiae and fracture risk assessment by FRAX (Switzerland). Results: K-citrate increased aBMD at lumbar spine from baseline by 1.7 ± 1.5% [95% confidence interval (CI) = 1.0-2.3, P < 0.001] net of placebo after 24 months. High-resolution peripheral quantitative computed tomography-measured trabecular densities increased at nondominant tibia (1.3 ± 1.3%, CI = 0.7-1.9, P < 0.001) and nondominant radius (2.0 ± 2.0%, CI = 1.4-2.7, P < 0.001). At nondominant radius, trabecular bone volume/tissue volume increased by 0.9 ± 0.8%, (CI = 0.1-1.7), trabecular thickness by 1.5 ± 1.6% (CI = 0.7-2.3), and trabecular number by 1.9 ± 1.8% (CI = 0.7-3.1, for all, P < 0.05). K-citrate diminished fracture prediction score by FRAX significantly in both sexes. Conclusions: Among a group of healthy elderly persons without osteoporosis, treatment with K-citrate for 24 months resulted in a significant increase in aBMD and volumetric BMD at several sites tested, while also improving bone microarchitecture. Based on the effect on fracture prediction, an effect on future fractures by K-citrate is possible.
There is a need to understand the role of nutrition, beyond calcium and vitamin D, in the treatment and prevention of osteoporosis in adults. Results regarding soy compounds on bone density and bone turnover are inconclusive perhaps due to differences in dose and composition or in study population characteristics. The skeletal benefit of black cohosh and red clover are unknown. Dehydroepiandrosterone (DHEA) use may benefit elderly individuals with low serum dehydroepiandrosterone-sulfate levels, but even in this group, there are inconsistent benefits to bone density (BMD). Higher fruit and vegetable intakes may relate to higher BMD. The skeletal benefit of flavonoids, carotenoids, omega-3-fatty acids, and vitamins A, C, E and K are limited to observational data or a few clinical trials, in some cases investigating pharmacologic doses. Given limited data, it would be better to get these nutrients from fruits and vegetables. Potassium bicarbonate may improve calcium homeostasis but with little impact on bone loss. High homocysteine may relate to fracture risk, but the skeletal benefit of each B vitamin is unclear. Magnesium supplementation is likely only required in persons with low magnesium levels. Data are very limited for the role of nutritional levels of boron, strontium, silicon and phosphorus in bone health. A nutrient rich diet with adequate fruits and vegetables will generally meet skeletal needs in healthy individuals. For most healthy adults, supplementation with nutrients other than calcium and vitamin D may not be required, except in those with chronic disease and the frail elderly.