Rachel , John , and Michael Y: Cardiovascular Calcification and Bone: A Comparison of The Effects of Dietary and Serum Calcium, Phosphorous, Magnesium and Vitamin D.


Osteoporosis and atherosclerosis are leading causes of morbidity and mortality in the Western world. Although these conditions commonly co-occur in older adults, growing evidence suggests an association between vascular calcification and skeletal fragility that is independent of age and other shared risk factors. Older adults with the greatest bone loss have the greatest progression of vascular calcification1,2 and the incidence of cardiovascular (CV) events is greater in women with lower bone mass3 and in men with higher levels of bone resorption4,5. The association between both pathologies also depends on the mechanisms involved in the regulation of bone and CV metabolism5. We have previously shown that the nutrients and micronutrients that benefit the CV system generally also benefit bone6-8. In this article we discuss the effect and interactions of the principal dietary bone minerals (calcium, phosphorus, magnesium) and vitamin D on CV calcification and bone health in principally older adults. Where these studies also investigated other aspects of CV health, we report these as well. Although other minerals, such as potassium, sodium, selenium and zinc are known to be involved in bone health, there are no human or animal studies investigating their association with CV calcification, so we have not included them. We have taken an effect on bone to mean an effect on at least one skeletal site but not necessarily all sites.


Calcium fulfils vital roles in the body, particularly with respect to cell signalling functions; for this reason it is critical that serum calcium be maintained in a very narrow range. There are two modes of intestinal calcium absorption: active transcellular absorption, mediated by 1,25(OH)2D binding to the intestinal vitamin D receptor (VDR), and passive paracellular absorption, dependent on the calcium gradient, with high intake stimulating increased absorption independent of 1,25(OH)2D9,10. Active calcium absorption decreases when serum 25(OH) D concentration is <20nmol/L and consequently low calcium intake aggravates the consequences of vitamin D deficiency9. 1,25(OH)2D also increases renal reabsorption of calcium and upregulates bone resorption by facilitating osteoclast maturation, thereby increasing serum calcium11. Animal studies demonstrate that maintaining normocalcaemia takes priority over skeletal integrity because of calcium’s multiple intracellular and extracellular roles12. Dietary sources of calcium are mainly dairy products, fish, legumes, grains and vegetables13,14.

CV calcification

Observational studies generally show little association of calcium intake, dietary or supplemental, with coronary artery calcification (CAC) or abdominal aortic calcification (AAC) incidence or extent in older adults4,15-18, although a large study showed that calcium intake was significantly higher in postmenopausal men and women without AAC at baseline and in women only after five years19. Koreans with the highest calcium intake (>840mg/d) also had improved serum lipid profiles20. Many studies of serum calcium show no association with calcification21-25, although some show a positive correlation with presence, extent and progression of AAC in older adults19,26-27, with mixed results for presence of CAC, although there may be an association with extent or progression18-19,28-29. Serum calcium was an independent predictor of calcified and mixed plaque but not non-calcified plaque29 and higher concentrations were associated with lower in-hospital mortality among MI patients30. Nevertheless, serum calcium levels often bear little relationship to intake, as is evidenced by the study by Wang et al, where higher serum calcium was associated with increased AAC but a higher calcium intake was found in those with no AAC19. Nunes has suggested that it is the deranged metabolism of calcium and phosphorus, rather than the intake, which may be promoting CV calcification, particularly in CKD31. Animal studies have shown that low calcium intake induces higher nephrocalcinosis and aortic calcium content, while high calcium intake is not generally associated with calcification in health32-34 but in rats with chronic kidney disease (CKD) and secondary hyperparathyroidism calcium supplementation increased arterial calcification35.

Figure 1

Mechanism by which low serum calcium (Ca), magnesium (Mg) or 1,25(OH)2D impacts the parathyroid gland, bone, kidney and the gut to raise serum Ca


In view of the recent concern by Bolland et al that elevated serum calcium or calcium supplementation, but not dietary calcium, might increase CV events36-38, a review and subsequent studies found no evidence of any significant effect of calcium supplementation on the risk of coronary artery disease (CAD), stroke, CVD events15,17,39. In fact, a systematic review showed a strong association between calcium malnutrition and risk of hypertension and CV events40, while 1g/d calcium supplementation was associated with lower CVD and CHD risk after four years41 and reduced mortality in women after 10 years42, with calcium supplementation protecting against vascular disease by lowering serum cholesterol level and blood pressure43-44.


Although osteoporosis appears to have little association with serum calcium45, a review of observational studies found an association of low calcium intake and osteoporosis risk40, with an intake threshold of <400mg/d46. This may only be a short-term association, possibly suggesting adaptation to a low calcium intake47. As with CV calcification, several recent meta-analyses and systematic reviews of studies of healthy adults have concluded that the evidence for an association between calcium intake and BMD or fracture risk was insufficiently clear48-51, although a Cochrane Review and recent studies have shown an effect of calcium supplementation on BMD but not fracture incidence in postmenopausal women, with an effective mean intake being >800mg/d17,52-53, although much higher intakes have reduced fracture risk in other studies17,54-55. Postmenopausal women possibly require a total intake of >1100mg/d56-58, although calcium may only be effective in the first five postmenopausal years59. Some of the inconsistent results may be due to the fact that few studies measure baseline calcium intake or status; supplementation in replete subjects is unlikely to have a benefit9. Furthermore, race may account for some of the mixed results; among postmenopausal women, there was a positive association between BMD and calcium intake in white but not Hispanic, black or Mexican-American women60, whereas among older men there was a correlation between BMD and calcium intake in blacks but not whites61. Where calcium intake has been found predictive of BMD, the necessary intake for bone health appears to be >800 mg/day.


Phosphate is critical for bone mineralisation but also for cell signalling and energy storage in the form of ATP, requiring strict control over blood concentrations, as with calcium62. The main dietary sources of organic phosphorus are animal and plant proteins63, while inorganic phosphorus is mostly seen in food preservatives or as phosphoric acid in colas; phosphoric acid may also bind with calcium in the intestine, so preventing calcium absorption64. Although up to 100% of inorganic phosphorus may be absorbed, only 40-60% of organic phosphorus is absorbed. Furthermore, much of plant phosphorus is in the form of phytate (myo-inositol hexakisphosphate), found principally in unrefined cereals and legumes, which can inhibit absorption of several minerals by forming non-digestible mineral complexes65-66. As with calcium, there are two mechanisms of phosphorus absorption: an active 1,25(OH)2D-dependent process, utilising sodium phosphate co-transporters, and a passive diffusional process dependent on the phosphorus gradient62,66-69. Phosphorus restriction can also increase synthesis of 1,25(OH)2D70. There are growing concerns that excess phosphorus intake from food additives and colas, with concomitant decrease in calcium intake from vegetables, in the general population may be a risk factor for CV disease, osteoporosis and mortality, possibly through induction of secondary hyperparathyroidism, even when serum phosphate remains within the normal range71.

CV calcification

In the few studies of the effect of dietary phosphorus on human CV calcification there is no association in older Koreans18, although animal studies show a positive association between phosphorus intake and aortic and renal calcification and atheroma incidence71-72. Two large studies by Linefsky et al found a significant association between baseline mean serum phosphate levels (>1.292mmol/l vs ≤0.969mmol/l) and baseline aortic valve calcification (AVC), mitral annulus calcification (MAC) and AAC presence but not with extent, progression or new development after a mean of 2.4 years; the association with AAC lost significance after adjustment25,73. These studies demonstrate that even a serum phosphate value within the reference range (0.8-1.4mmol/l) is associated with CV calcification, as well as increased CV risk [66]. Studies of older adults and CKD patients also found a significant association between higher serum phosphate and presence and extent of calcification18,21,22,26,28,29, with each 0.0323mmol/l rise in serum phosphorus being associated with 6.1% higher odds of having CAC21. Wang et al found a gender difference; in postmenopausal women, serum phosphate was significantly higher (1.15 vs 1.17 mmol/l) in subjects with AAC, while in older men there was no association19. Elevated serum phosphate was also associated with coronary obstructive lesions and CV events, although results for mortality were mixed21,74-75. A similar association with arterial and valvular calcification and increased carotid intima/media thickness (cIMT) is generally seen in CKD, although the serum phosphate levels tend to be considerably higher23,76-79 and are due to failure to excrete excess phosphate, which may be the driver for ectopic calcification80. In CKD, arterial calcification can be suppressed by reducing serum phosphate levels, even in the presence of high serum calcium and 1,25-dihydroxyvitamin D levels81. CKD rats showed phosphorus intake-dependent increases in markers of inflammation and oxidative stress as well as CV calcification and mortality82, while VSMCs cultured in normal levels of phosphorus do not calcify79 but high inorganic phosphorus can induce calcification, endothelial dysfunction and increased markers of inflammation21,79,82,83.

Figure 2

Mechanism by which high serum phosphate (P) impacts the parathyroid gland and kidney to lower serum P



Results of adult human studies show mixed results for associations between total phosphorus intake and osteoporosis or fractures84-86, although inorganic phosphorus intake from colas induced a higher incidence of osteopenia and lower BMD among women only; since this was not seen with other soft drinks it is likely to be attributable to phosphoric acid64. Among healthy women, dietary and serum phosphorus were generally not associated with BMD or markers of bone formation or resorption45,85,87. Phosphorus supplementation in young women resulted in decreased markers of bone formation and increased markers of resorption88 but had no adverse effect on young men89. A further intervention study found that the adverse effects of high phosphorus supplementation could be negated by high calcium supplementation90. Animal studies show that diets creating either a phosphorus excess or deficiency lower BMD and bone mineralisation71,91.


Magnesium is an essential mineral, acting as cofactor in more than 300 enzymatic reactions. It is a natural calcium channel blocker and plays an important role in CV, neurological and metabolic functions, although approximately 60% of body magnesium is found in bone92. Dietary sources include legumes, vegetables, nuts, seeds, fruits, grains, fish and dairy foods93. As with calcium and phosphorus, there is a vitamin D-dependent intestinal absorption and gradient-driven absorption94.

Ectopic calcification

The principal intake study found that CV calcification was lowest in the quartile with intake ranging from 384-669mg/d95, while higher intake was inversely associated with stroke risk39, diabetes incidence and hypertension96. The only studies of blood concentrations involve dialysis patients and show a clear association between lower serum magnesium (1.1056mmol/l vs 1.241mmol/l) and peripheral artery calcification97-98 and MAC99, the protective amount being above the reference range (upper limit 1.2mmol/l), although this should not be extrapolated to non-renal patients. Serum magnesium was also inversely correlated with cIMT and aortic pulse wave velocity in renal and non-renal patients100. In animals, a low magnesium diet increased cardiac magnesium and calcium deposition72,100-102 but the CV and renal calcification was worse when low magnesium intake was combined with high phosphorus102-103. Experimental magnesium deficiency also induced arterial damage, hypertriglyceridaemia and a decrease in HDL cholesterol transport104. A high magnesium intake, however, was associated with a reduction in plasma cholesterol and triglycerides in rats105. There are no trials of magnesium supplementation on CV calcification in humans but in renal patients supplementation resulted in significantly lower cIMT106, while in animals supplementation dose-dependently lowered myocardial, carotid and aortic calcium content107,108. Similarly, in vitro studies showed that increasing magnesium concentration reduced calcification in VSMC83,100.


Dietary and serum, but not red cell, magnesium were generally lower among the elderly with osteoporosis45,86,109 and among healthy older adults, magnesium intake was positively associated with BMD, BMC and bone mass86,110-111, with an intake of >422.5mg/d vs <206.5 mg/d improving BMD110. A large multiethnic study found that this association may apply to older whites but not blacks112. Some studies also found an association with BMD in younger women113-114. Study results are mixed with respect to intake and fracture risk84,110,115 and among Japanese subjects low serum magnesium was associated with increased fracture incidence116. Short term intervention studies show that 1830mg/d magnesium citrate significantly decreased levels of urinary deoxypyridinoline (a marker of bone resorption) in postmenopausal osteoporotic women with normal baseline serum magnesium and calcium, while concentrations of serum osteocalcin (a marker of bone turnover) were increased117 but there was no effect in young women118. Longer studies of postmenopausal women with low BMD showed that magnesium supplementation increased BMD119-120.

Figure 3

Mechanism by which high serum phosphate (P) triggers release of FGF23 to lower serum P


Vitamin D

Vitamin D is a steroid hormone which has multiple roles in the body, in particular an autocrine function, which acts to promote skeletal health, and an endocrine function, which includes maintenance of serum calcium within a narrow range121. Since serum calcium homeostasis is of vital importance, the endocrine function can often operate to the detriment of the autocrine function122, which may account for the lack of clear results in vitamin D studies. Low serum calcium or phosphate triggers the synthesis of the vitamin D metabolite 1,25(OH)2D in kidney and bone, which in turn binds to the intestinal vitamin D receptor (VDR) and increases intestinal calcium10,123 , phosphorus62,67-69 and magnesium94 absorption and renal reabsorption but also inhibits bone mineralisation62 and upregulates bone resorption by facilitating osteoclast maturation to release calcium and phosphate, thereby increasing serum concentrations11. Active calcium absorption decreases when serum 25(OH) D concentration is <20nmol/L and consequently low calcium intake aggravates the consequences of vitamin D deficiency123. There is a decreasing ability with age to synthesise either 25(OH)D or 1,25(OH)2D as well as intestinal resistance to its action124-125; it appears that the optimal level of serum 25(OH) D for calcium absorption is >80nmol/l in postmenopausal women126. Vitamin D also has key roles in CV health, as indicated by the presence of the VDR in cardiomyocytes, vascular endothelial cells and VSMCs127. The principal source of vitamin D is sunlight on skin but foods such as egg yolk, offal, oily fish and shellfish also provide some intake, as well as fortified foods124,125.

Ectopic calcification

There are no human intake studies with respect to CV calcification, probably because dietary vitamin D provides only a relatively small contribution to serum 25(OH)D. Animal studies, however, show that high vitamin D intake can induce CV calcification and impair endothelial function128,129 but they also show that a vitamin D deficient diet can induce an increase in calcified lesions130-132, indicating that both excess and deficiency are detrimental. Several epidemiological studies measuring serum 25(OH)D demonstrate an absence of association with presence or extent of CAC, MAC, cIMT, degree of carotid stenosis or mean arterial pressure22,133-135, although patients with calcific aortic stenosis136 and poor coronary collateral circulation137 had significantly lower serum 25(OH)D. After three years serum 25(OH)D was associated with new CAC development, but not CAC progression, with those with serum 25(OH)D of <37.55nmol/l having increased risk133. The association is usually clearer in those with previously diagnosed disease. In CKD patients, arterial calcification was significantly inversely associated with serum 25(OH)D24 and a high peripheral arterial calcification score was significantly associated with lower 25(OH)D concentrations138. Similarly in type 1 diabetics, serum 25(OH)D <49.9nmol/l was associated with the presence and development of CAC after 3 years139, with valvular calcification in dilated cardiomyopathy patients (serum 25(OH)D <75nmol/l)140 and with the calcification score in peripheral arterial disease27. Likewise with respect to serum 1,25(OH)2D, some studies show no association with CAC extent or progression133,141, although in subjects at risk for CHD, serum 1,25(OH)2D was inversely correlated with the extent of calcification142.

There have been few intervention studies of vitamin D alone but in CKD patients the incidence of aortic calcification was significantly lower in treated patients143, while in heart failure, 4000IU/d for six months significantly improved the left ventricular ejection fraction144. Trials of vitamin D supplementation combined with calcium showed that up to 1000g/d calcium plus 400 IU/d vitamin D3 did not affect CAC scores or incidence of myocardial infarction (MI), CHD mortality or stroke in postmenopausal women145-146, although there was an improvement in dyslipidaemia147; this lack of result may be because the vitamin D dose was low. Nevertheless, although a 2011 systematic review found that serum 25(OH)D was not significantly associated with mortality, MI or stroke148, a meta-analysis of RCTs found that vitamin D supplementation for at least three years significantly decreased all-cause mortality149.


A 2006 systematic review and more recent studies of older adults showed that a vitamin D intake of ≥400 IU/d was associated with reduced bone loss 150-152 but with respect to fracture incidence, there appears to be little association with vitamin D intake115. Two large reviews found that in older adults, serum 25(OH)D was positively associated with BMD but there was inconsistent evidence for an association with fractures153. In elderly postmenopausal women, those with serum 25(OH) D levels <50 nmol/L had increased fracture risk, bone loss and mortality, leading to recommendations that 50nmol/L should be the minimum level to ensure optimum bone health, below which supplementation is recommended at 800-1000IU/d but above this threshold there was no clear evidence for additional benefit except in fragile elderly subjects, for whom serum 25(OH) D should be ≥75nmol/l154. Recent Korean studies confirm the positive association, which may not be linear155 and indicate that BMD increases until 25(OH)D ≥70mmol/l in men and 50 nmol/l in women156. Ethnicity may have a bearing on the effect of vitamin D. A prospective study showed that higher 25(OH)D levels were associated with a lower risk of fracture in white women but a higher risk in black and Asian women and no association in Hispanic or Native American women157; the NHANES study showed that mean 25(OH)D levels were highest in whites and lowest in blacks yet blacks had the highest BMD and whites had the lowest158.

When additionally considering calcium intake, the combination of higher vitamin D and calcium were associated with higher BMD in young adults159 and reduced osteoporosis risk in postmenopausal women47, with the optimum dose for fracture reduction being 700-800IU/d vitamin D3 with 500-1200mg/d calcium153. Animal studies confirm that a diet deficient in calcium and vitamin D lowers BMD and increases urinary excretion of markers of bone resorption, not seen in calcium or vitamin D deficiency alone160. In humans, BMD and BMC loss and fracture risk were more consistently inversely associated with calcium intake and serum 25(OH)D taken together among all agegroups than either nutrient taken alone150,155. Three recent reviews and meta-analyses of intervention studies found that vitamin D supplementation alone did not prevent fractures or increase BMD; the two reviews found a protective effect of vitamin D with calcium but results of the meta-analysis depend on the authors’ ‘futility boundary’161-163. A further meta-analysis found that in older adults, supplementation of 800IU/d could significantly reduce hip fractures and associated deaths over one year164.

Other multinutrient interactions

Lappe and Heaney point out that nutrient trials may fail because of inadequate attention to co-nutrient optimisation, including protein165. One of the most important mineral partnerships is that of calcium and phosphorus, with the calcium/phosphorus ratio in bone being 2.2:1166. An intake ratio of <1.0 was associated with nephrocalcinosis in rats but increasing the ratio to 1.3 inhibited calcification development167, while a low intake ratio increased osteoporosis risk in Koreans168 and increased bone resorption markers169 but a ratio of at least ≥0.74 benefited bone among younger females87,170. Although phosphorus restriction increases serum ionised calcium70, phosphorus supplementation was also associated with decreased urinary calcium excretion126,171, suggesting that calcium is retained to bind the phosphorus. There is also a strong interaction between calcium and magnesium, with low magnesium intake in animals increasing serum calcium, the calcium/phosphate ratio and calcium deposition in bone172-173 but with high calcium intake, serum and tissue magnesium was lower, suggesting decreased absorption174. High magnesium intake in calcium sufficiency, however, significantly improved all bone parameters compared to calcium insufficiency and when supplemented together, there was a significant improvement to all bone parameters175. There is competitive inhibition of gradient-dependent intestinal absorption, not only between magnesium and calcium67,94 but also between magnesium and phosphorus provided calcium is adequate but magnesium absorption may increase at the expense of phosphorus when serum calcium is low94. Magnesium depletion is associated with increased serum ionised magnesium and calcium and decreased ionised phosphate101,102. Magnesium also interacts with vitamin D, such that magnesium deficiency impairs the synthesis of 1,25(OH)2D even during dietary calcium deprivation176 and can lead on to resistance to 1,25(OH)2D177.


As well as vitamin D, additional regulators of CV calcification and bone mineralisation include parathyroid hormone (PTH)178 and fibroblast growth factor 23 (FGF23), a phosphotonin secreted from bone, which appears to be a counter-regulatory hormone for vitamin D179. Figures 1-3 demonstrate how all three are involved in the regulation of serum calcium, phosphate and magnesium. Optimal PTH concentrations have been found when 25(OH)D ≥80nmol/l180,181, while elevated FGF23 was associated with the CAC score in haemodialysis patients182 and even among healthy subjects, the highest FGF23 quartile was associated with higher CAC scores and greater risk of heart failure and CHD183. Elevated serum phosphate can impair endothelial function, as evidenced by decreased vasodilatation, and may promote transdifferentation of VSMCs to osteoblast-like cells71.


Although most studies show little association between calcium intake and CV calcification or BMD and fracture risk, the large study showing a positive correlation between higher intake and absence of AAC and the review showing an association between low intake and osteoporosis indicate that a higher intake is preferable. BMD studies indicate that this should be >800mg/d, with 1100mg/d for postmenopausal women, although larger doses were required for fracture prevention. Possibly the studies show a lack of association because even in the higher quartiles, intake is still too low. Serum calcium studies also generally show no association with CV calcification or bone, although a few show a positive association with AAC, but an association between serum calcium and bone would not be expected, since bone is a calcium reservoir to maintain serum levels. Bone studies also highlight the fact that ethnicity may distort results, which may be equally applicable to CV studies. There is no evidence that calcium supplementation increases CV risk; in fact calcium appears beneficial for prevention of CV events and mortality and can lower cholesterol and blood pressure.

Higher dietary and serum phosphorus may promote CV calcification even when serum phosphate is within normal range. Results of phosphorus intake and bone studies are mixed, possibly because phosphorus is necessary for healthy bone but the phosphoric acid in colas may pose a particular risk for bone loss in women. It appears that healthy individuals can adjust to a wide range of phosphorus consumption but have little adaptive ability for low calcium intake, indicating that the calcium/phosphorus intake ratio is more critical than the absolute phosphorus intake184; any detrimental effect of high phosphorus intake can be negated by increasing calcium intake. Dietary and serum magnesium intake shows a strong inverse correlation with CV calcification, osteoporosis and bone loss, as well as with stroke incidence, cIMT and conventional rsk factors; CV calcification is minimised with intake in the quartile ranging from 384-669mg/d but this association may only apply to Caucasians. Calcification resulting from a low magnesium intake is particularly severe in animals when combined with high phosphorus intake. Although human trials are lacking, magnesium supplementation in animals significantly lowered CV calcification. In bone, magnesium supplementation increased BMD and improved markers of bone turnover.

Although human observational studies for vitamin D intake and CV calcification are lacking, animal studies show a U-shaped dose/response curve for intake, while bone studies found that intake of >/=400IU/d is required to reduce bone loss. Serum 25(OH)D is generally not correlated with CV calcification, except in CKD and other already-diagnosed conditions, where it is inversely associated, but in bone, serum 25(OH)D is positively associated with BMD. Intervention studies show reduced CV calcification in CKD, improved ventricular function in heart failure and lower mortality in longer term studies but no effect on CV calcification in healthy postmenopausal women, either alone or when accompanied by calcium, although the vitamin D dose was low (400IU/d). The vitamin D/calcium combination is beneficial to bone, however, provided the vitamin D dose is adequate. Bone studies indicate that supplementation of >/=800IU/d is required to bring serum 25(OH)D up to 50nmol/l in healthy adults or >/=75nmol/l in the fragile elderly. Ethnicity may again affect results, with higher 25(OH)D giving a higher fracture risk in black and Asian women. It is difficult to assess the CV or bone effects of vitamin D alone, since its predominant function is to maintain serum calcium homeostasis and it will do this to the detriment of bone or arteries if necessary; baseline serum calcium is seldom measured in these studies.

These studies highlight the interactions between the different micronutrients and point up the need for a calcium phosphorus intake in the ratio of >1 for bone health, which may also translate to arteries. Because of the competitive inhibition of absorption if intake of one mineral is imbalanced, it is important that adequate, but not excessive, intake of all bone minerals is maintained for both artery and bone health.


This review has firstly demonstrated that a mineral and vitamin D intake that is beneficial for bone is also generally protective against CV calcification. In principal this involves ensuring an adequate intake through diet or supplementation of each mineral and, in particular, supplementing sufficient calcium to balance any increased phosphorus intake to avoid upregulating PTH and to prevent a catabolic effect of vitamin D supplementation on bone to maintain serum calcium. These relationships may, however, not hold among African Americans and Asians. It has secondly shown the striking inter-relationship between the three bone minerals and vitamin D. This is particularly true with calcium, magnesium and vitamin D, where one can, to a certain extent, substitute for the other in the short term in maintaining bone health. Bone studies show limited effect when considering calcium and vitamin D separately but when supplemented together there is a significant protective effect. The competitive inhibition of absorption between all three minerals further emphasises that the diet should contain adequate levels of all three. The concern over the effect of supplemental calcium and CV events appears unnecessary since there is no evidence of any significant detrimental effects, whereas calcium supplementation may in fact be protective.



Kiel DP, Kauppila LI, Cupples LA, Hannan MT, O'Donnell CJ, Wilson PW Bone loss and the progression of abdominal aortic calcification over a 25 year period: the Framingham Heart Study. Calcif Tissue Int 2001; 68: 271–6


Zhou R, Zhou H, Cui M, Chen L, Xu J The Association between Aortic Calcification and Fracture Risk in Postmenopausal Women in China: The Prospective Chongqing Osteoporosis Study. PLoS One 2014 May 9; 95–e93882


Samelson EJ, Kiel DP, Broe KE, Zhang Y, Cupples LA, Hannan MT, Wilson PW, Levy D, Williams SA, Vaccarino V Metacarpal cortical area and risk of coronary heart disease: the Framingham Study. Am J Epidemiol 2004; 159: 589–95


Samelson EJ, Booth SL, Fox CS, Tucker KL, Wang TJ, Hoffmann U, Cupples LA, O'Donnell CJ, Kiel DP Calcium intake is not associated with increased coronary artery calcification: the Framingham Study. Am J Clin Nutr 2012; Dec9661274–80


Szulc P Association between cardiovascular diseases and osteoporosis-reappraisal. Bonekey Rep 2012; Aug8: 1–144


Nicoll R, McLaren Howard J, Henein M Cardiovascular and renal calcification and bone: A comparison of the effects of dietary fatty acids. International Cardiovascular Forum 2014; 3: 127–131


Nicoll R, McLaren Howard J, Henein M Ectopic calcification and bone: A comparison of the effects of dietary carbohydrates, sugars and protein. International Cardiovascular Forum 2014; 4: In press


Nicoll R, McLaren Howard J, Henein M Cardiovascular calcification and bone: A comparison of the effects of dietary antioxidants. International Cardiovascular Forum 2014; 5: In press


Lips P Interaction between vitamin D and calcium’. Scand J Clin Lab Invest Suppl 2012; 243: 60–4


Dawson-Hughes B, Bischoff-Ferrari HA ‘Therapy of osteoporosis with calcium and vitamin D’. J Bone Miner Res 2007; 22: Suppl 2V59–V63


Weaver CM ‘2003 W.O. Atwater Memorial Lecture: Defining Nutrient Requirements from a Perspective of Bone-Related Nutrients’. Am Soc Nutr Sci 2003; 133: 4063–6


Brown EM Role of the calcium-sensing receptor in extracellular calcium homeostasis. Best Pract Res Clin Endocrinol Metab 2013 Jun; 273333–43


Cook AJ, Friday JE Food mixture or ingredient sources for dietary calcium: shifts in food group contributions using four grouping protocols. J Am Diet Assoc 2003;


Ishida H Nutrition and bone health Calcium-rich foods and bone. Clin Calcium 2009; Nov19111670–7


Spence LA, Weaver CM Calcium intake, vascular calcification, and vascular disease. Nutr Rev 2013; Jan71115–22


Kim JH, Yoon JW, Kim KW, Lee EJ, Lee W, Cho SH, Shin CS Increased dietary calcium intake is not associated with coronary artery calcification. Int J Cardiol 2012; Jun141573429–31


Radford LT, Bolland MJ, Mason B, Horne A, Gamble GD, Grey A, Reid IR The Auckland calcium study: 5-year post-trial follow-up. Osteoporos Int 2014; Jan251297–304


Kwak S, Kim JS, Choi Y, Chang Y, Kwon MJ, Jung JG, Jeong C, Ahn J, Kim HS, Shin H, Ryu S Dietary Intake of Calcium and Phosphorus and Serum Concentration in Relation to the Risk of Coronary Artery Calcification in Asymptomatic Adults. Arterioscler Thromb Vasc Biol 2014; Jun12[Epub ahead of print]


Wang TK, Bolland MJ, van Pelt NC, Horne AM, Mason BH, Ames RW, Grey AB, Ruygrok PN, Gamble GD, Reid IR Relationships between vascular calcification, calcium metabolism, bone density, and fractures. J Bone Miner Res 2010; Dec25122777–85


Kim JH, Yoon JW, Kim KW, Lee EJ, Lee W, Cho SH, Shin CS Increased dietary calcium intake is not associated with coronary artery calcification. Int J Cardiol 2012; Jun141573429–31


Cancela AL, Santos RD, Titan SM, Goldenstein PT, Rochitte CE, Lemos PA, dos Reis LM, Graciolli FG, Jorgetti V, Moysés RM Phosphorus is associated with coronary artery disease in patients with preserved renal function. PLoS One 2012; 75e36883


Park KS, Chang JW, Kim TY, Kim HW, Lee EK, Kim HS, Yang WS, Kim SB, Park SK, Lee SK, Park JS Lower concentrations of serum phosphorus within the normal range could be associated with less calcification of the coronary artery in Koreans with normal renal function. Am J Clin Nutr 2011; Dec9461465–70


Srivaths PR, Goldstein SL, Silverstein DM, Krishnamurthy R, Brewer ED Elevated FGF 23 and phosphorus are associated with coronary calcification in hemodialysis patients. Pediatr Nephrol 2011 Jun; 266945–51


García-Canton C, Bosch E, Ramírez A, Gonzalez Y, Auyanet I, Guerra R, Perez MA, Fernández E, Toledo A, Lago M, Checa MD Vascular calcification and 25-hydroxyvitamin D levels in non-dialysis patients with chronic kidney disease stages 4 and 5. Nephrol Dial Transplant 2011; Jul2672250–6


Linefsky JP, O'Brien KD, Katz R, de Boer IH, Barasch E, Jenny NS, Siscovick DS, Kestenbaum B Association of serum phosphate levels with aortic valve sclerosis and annular calcification: the cardiovascular health study. J Am Coll Cardiol 2011; Jul12583291–7


Figueiredo CP, Rajamannan NM, Lopes JB, Caparbo VF, Takayama L, Kuroishi ME, Oliveira IS, Menezes PR, Scazufca M, Bonfá E, Pereira RM Serum phosphate and hip bone mineral density as additional factors for high vascular calcification scores in a community-dwelling: the São Paulo Ageing & Health Study (SPAH). Bone 2013; Jan521354–9


Zagura M, Serg M, Kampus P, Zilmer M, Eha J, Unt E, Lieberg J, Cockcroft JR, Kals J Aortic stiffness and vitamin D are independent markers of aortic calcification in patients with peripheral arterial disease and in healthy subjects. Eur J Vasc Endovasc Surg 2011; Nov425689–95


Tuttle KR, Short RA Longitudinal relationships among coronary artery calcification, serum phosphorus, and kidney function. Clin J Am Soc Nephrol 2009; Dec4121968–73


Shin S, Kim KJ, Chang HJ, Cho I, Kim YJ, Choi BW, Rhee Y, Lim SK, Yang WI, Shim CY, Ha JW, Jang Y, Chung N Impact of serum calcium and phosphate on coronary atherosclerosis detected by cardiac computed tomography. Eur Heart J 2012; Nov33222873–81


Lu X, Wang Y, Meng H, Chen P, Huang Y, Wang Z, Zhou N, Li C, Wang L, Jia E, Yang Z Association of Admission Serum Calcium Levels and In-Hospital Mortality in Patients with Acute ST-Elevated Myocardial Infarction: An Eight-Year, Single-Center Study in China. PLoS One 2014; Jun1396e99895


Nunes JP The case for dietary calcium restriction in patients with atherosclerosis. Med Hypotheses 2005; 653521–4


Agata U, Park JH, Hattori S, Iimura Y, Ezawa I, Akimoto T, Omi N ‘The effect of different amounts of calcium intake on bone metabolism and arterial calcification in ovariectomised rats’. J Nutr Sci Vitaminol (Tokyo). 2013; 59129–36


Phillips JC, Bex C, Mendis D, Gangolli SD Studies on the mechanism of diet-induced nephrocalcinosis: calcium and phosphorus metabolism in the female rat. Food Chem Toxicol 1986; Apr244283–8


Hsu HH, Culley NC Effects of dietary calcium on atherosclerosis, aortic calcification, and icterus in rabbits fed a supplemental cholesterol diet. Lipids Health Dis 2006; Jun235: 16


Moe SM, Chen NX, Newman CL, Gattone VH 2nd,, Organ JM,, Chen X, Allen MR A Comparison of Calcium to Zoledronic Acid for Improvement of Cortical Bone in an Animal Model of CKD. J Bone Miner Res 2014; Apr294902–10


Bolland MJ, Barber PA, Doughty RN et al Vascular events in healthy older women receiving calcium supplementation: randomised controlled trial. BMJ 2008; 3367638262–6


Bolland MJ, Avenell A, Baron JA et al Effect of calcium supplements on risk of myocardial infarction and cardiovascular events: meta-analysis. BMJ 2010; 341: c3691


Bolland MJ, Grey A, Avenell A, Gamble GD, Reid IR Calcium supplements with or without vitamin d and risk of cardiovascular events: reanalysis of the women’s health initiative limited access dataset and meta-analysis. BMJ 2011; 342: d2040


Sluijs I, Czernichow S, Beulens JW, Boer JM, van der Schouw YT, Verschuren WM, Grobbee DE Intakes of Potassium, Magnesium, and Calcium and Risk of Stroke. Stroke 2014; Feb11[Epub ahead of print]


Peterlik M, Kállay E, Cross HS Calcium nutrition and extracellular calcium sensing: relevance for the pathogenesis of osteoporosis, cancer and cardiovascular diseases. Nutrients 2013; Jan2251302–27


Paik JM, Curhan GC, Sun Q, Rexrode KM, Manson JE, Rimm EB, Taylor EN Calcium supplement intake and risk of cardiovascular disease in women. Osteoporos Int 2014; May7[Epub ahead of print]


Langsetmo L, Berger C, Kreiger N, Kovacs CS, Hanley DA, Jamal SA, Whiting SJ, Genest J, Morin SN, Hodsman A, Prior JC, Lentle B, Patel MS, Brown JP, Anastasiades T, Towheed T, Josse RG, Papaioannou A, Adachi JD, Leslie WD, Davison KS, Goltzman D CaMos Group. Calcium and vitamin D intake and mortality: results from the Canadian Multicentre Osteoporosis Study (CaMos). J Clin Endocrinol Metab 2013; Jul9873010–8


Reid IR, Mason B, Horne A et al Effects of calcium supplementation on serum lipid concentrations in normal older women: a randomized controlled trial. Am J Med 112: 52002; pp. 343–347


Griffith LE, Guyatt GH, Cook RJ, Bucher HC, Cook DJ The influence of dietary and nondietary calcium supplementation on blood pressure: an updated metaanalysis of randomized controlled trials. Am J Hypertens 1999; 121 Pt 184–92


Okyay E, Ertugrul C, Acar B, Sisman AR, Onvural B, Ozaksoy D Comparative evaluation of serum levels of main minerals and postmenopausal osteoporosis. Maturitas 2013; Dec764320–5


Kung AW, Lee KK, Ho AY, Tang G, Luk KD Ten-year risk of osteoporotic fractures in postmenopausal Chinese women according to clinical risk factors and BMD T-scores: a prospective study. J Bone Miner Res 2007; Jul2271080–7


Nieves JW, Barrett-Connor E, Siris ES, Zion M, Barlas S, Chen YT Calcium and vitamin D intake influence bone mass, but not short-term fracture risk, in Caucasian postmenopausal women from the National Osteoporosis Risk Assessment (NORA) study. Osteoporos Int 2008; May195673–9


Papaioannou A, Kennedy CC, Cranney A, Hawker G, Brown JP, Kaiser SM, Leslie WD, O'Brien CJ, Sawka AM, Khan A, Siminoski K, Tarulli G, Webster D, McGowan J, Adachi JD Risk factors for low BMD in healthy men age 50 years or older: a systematic review. Osteoporos Int 2009; Apr204507–18


Moyer VA on behalf of the US Preventive Services Task Force. ‘Vitamin D and calcium supplementation to prevent fractures in adults: US Preventive Services Task Force Recommendation Statement’. Ann Intern Med 2013; Epub ahead of print


Waugh EJ, Lam MA, Hawker GA, McGowan J, Papaioannou A, Cheung AM, Hodsman AB, Leslie WD, Siminoski K, Jamal SA Perimenopause BMD Guidelines Subcommittee of Osteoporosis Canada. Risk factors for low bone mass in healthy 40-60 year old women: a systematic review of the literature. Osteoporos Int 2009; Jan2011–21


Bischoff-Ferrari HA, Dawson-Hughes B, Baron JA, Buckhardt P, Li R, Spiegelman D et al ‘Calcium intake and hip fracture risk in men and women: a meta-analysis of prospective cohort studies and randomised controlled trials’. Am J Clin Nutr 2007; 8661780–90


Shea B, Wells G, Cranney A, Zytaruk N, Robinson V, Griffith L, Hamel C, Ortiz Z, Peterson J, Adachi J, Tugwell P, Guyatt G Osteoporosis Methodology Group; Osteoporosis Research Advisory Group. Calcium supplementation on bone loss in postmenopausal women. Cochrane Database Syst Rev 2004; 1CD004526


Nakamura K, Saito T, Kobayashi R, Oshiki R, Kitamura K, Oyama M et al ‘Effect of low-dose calcium supplements on bone loss in perimenopausal and postmenopausal Asian women: a randomised controlled trial’. J Bone Mineral Res 2012; 27112264–70


Dionyssiotis Y, Paspati I, Trovas G, Galanos A, Lyritis GP Association of physical exercise and calcium intake with bone mass measured by quantitative ultrasound. BMC Womens Health. 2010; Apr7: 10–12


Babaroutsi E, Magkos F, Manios Y, Sidossis LS Body mass index, calcium intake, and physical activity affect calcaneal ultrasound in healthy Greek males in an age-dependent and parameter-specific manner. J Bone Miner Metab 2005; 232157–66


Ho SC, Chen YM, Woo JL, Lam SS High habitual calcium intake attenuates bone loss in early postmenopausal Chinese women: an 18-month follow-up study. J Clin Endocrinol Metab 2004; May89(5)2166–70


Uusi-Rasi K, Kärkkäinen MU, Lamberg-Allardt CJ Calcium intake in health maintenance - a systematic review. Food Nutr Res. 2013; May16–57


Nordin BE The effect of calcium supplementation on bone loss in 32 controlled trials in postmenopausal women. Osteoporos Int 2009; Dec20122135–43


Anderson JJ, Roggenkamp KJ, Suchindran CM Calcium intakes and femoral and lumbar bone density of elderly U.S. men and women: National Health and Nutrition Examination Survey 2005-2006 analysis. J Clin Endocrinol Metab 2012; Dec97124531–9


Wang MC, Dixon LB Socioeconomic influences on bone health in postmenopausal women: findings from NHANES III, 1988-1994. Osteoporos Int 2006; Jan17191–8


Jaime PC, Latorre Mdo R, Florindo AA, Tanaka T, Zerbini CA Dietary intake of Brazilian black and white men and its relationship to the bone mineral density of the femoral neck. Sao Paulo Med J 2006; Sep71245267–70


Civitelli R, Ziambaras K ‘Calcium and phosphate homeostasis: concerted interplay of new regulators’. J Endocrinol Invest 2011; 34: (7 Suppl)3–7


Kremsdorf RA, Hoofnagle AN, Kratz M, Weigle DS, Callahan HS, Purnell JQ et al ‘Effects of a high protein diet on regulation of phosphorus homeostasis’. J Clin Endocrinol Metab. 2013 Epub ahead of print


Tucker KL Osteoporosis prevention and nutrition. Curr Osteopor Rep 2009; 7: 111–117


Gibson RS, Bailey KB, Gibbs M, Ferguson EL ‘A review of phytate, iron, zinc and calcium concentrations in plant-based complementary foods used in low-income countries and implications for bioavailability’. Food Nutr Bull 2010; 31: (2 Suppl)S134–46


McCarty MF, DiNicolantonio JJ Bioavailable dietary phosphate, a mediator of cardiovascular disease, may be decreased with plant-based diets, phosphate binders, niacin, and avoidance of phosphate additives. Nutrition 2014; July-August3078739–747


Levine BS, Walling MW, Coburn JW ‘Effect of vitamin D sterols and dietary magnesium on calcium and phosphorus homeostasis’. Am J Physiol 1981; 241(1)E35–41


Kurabayashi M Role of calcium and phosphate in atherosclerosis and vascular calcification. Clin Calcium 2013; Apr234489–96


Christakos S ‘Recent advances in our understanding of 1,25-dihydroxyvitamin D3 regulation of intestinal calcium absorption’. Arch Biochem Biophys 2012; 523: 73–76


Bushinsky DA, Nalbantian-Brandt C, Favus MJ ‘Elevated Ca2+ does not inhibit the 1,25(OH)2D3 response to phosphorus restriction’. Am J Physiol 1989; 256(2 Pt2)F285–9


Calvo MS, Uribarri J Public Health impact of dietary phosphorus excess on bone and cardiovascular health in the general population. Am J Clin Nutr 2013 Epub ahead of print.


Ritskes-Hoitinga J, Lemmens AG, Beynen AC Nutrition and kidney calcification in rats. Lab Anim 1989; Oct234313–8


Linefsky JP, O'Brien KD, Sachs M, Katz R, Eng J, Michos ED, Budoff MJ, de Boer I, Kestenbaum B Serum phosphate is associated with aortic valve calcification in the Multi-ethnic Study of Atherosclerosis (MESA). Atherosclerosis 2014; Jan212332331–337


Håglin L, Törnkvist B, Bäckman L Prediction of all-cause mortality in a patient population with hypertension and type 2 DM by using traditional risk factors and serum-phosphate,-calcium and-magnesium. Acta Diabetol 2007; Sep443138–43


Cubbon RM, Thomas CH, Drozd M, Gierula J, Jamil HA, Byrom R, Barth JH, Kearney MT, Witte KK, Calcium phosphate and calcium phosphate product are markers of outcome in patients with chronic heart failure. J Nephrol 2014 Mar 11. [Epub ahead of print] Done


Sharma VK, Dwivedi P, Dubey AK Correlation of serum phosphate with carotid intimal-medial thickness in chronic kidney disease patients. Indian J Nephrol 2014; Jan24115–9


Adeney KL, Siscovick DS, Ix JH, Seliger SL, Shlipak MG, Jenny NS, Kestenbaum BR Association of serum phosphate with vascular and valvular calcification in moderate CKD. J Am Soc Nephrol 2009; Feb202381–7


Rroji M, Seferi S, Cafka M, Petrela E, Likaj E, Barbullushi M, Thereska N, Spasovski G Is residual renal function and better phosphate control in peritoneal dialysis an answer for the lower prevalence of valve calcification compared to hemodialysis patients? Int Urol Nephrol. 2014; Jan46(1)175–82


Nishizawa Y, Jono S, Ishimura E, Shioi A Hyperphosphatemia and vascular calcification in end-stage renal disease. J Ren Nutr 2005; Jan151178–82


Craver L, Dusso A, Martinez-Alonso M, Sarro F, Valdivielso JM, Fernández E A low fractional excretion of Phosphate/Fgf23 ratio is associated with severe abdominal Aortic calcification in stage 3 and 4 kidney disease patients. BMC Nephrol 2013; Oct12: 14–221


Razzaque MS Phosphate toxicity and vascular mineralization. Contrib Nephrol 2013; 180: 74–85


Yamada S, Tokumoto M, Tatsumoto N, Taniguchi M, Noguchi H, Nakano T, Masutani K, Ooboshi H, Tsuruya K, Kitazono T Phosphate overload directly induces systemic inflammation and malnutrition as well as vascular calcification in uremia. Am J Physiol Renal Physiol 2014; Jun15306(12)F1418–28


Louvet L, Buchel J, Steppan S, Passlick-Deetjen J, Massy ZA ‘Magnesium prevents phosphate-induced calcification in human aortic vascular smooth muscle cells’. Nephrol Dial Transplant. Epub ahead of print


Pinheiro MM, Schuch NJ, Genaro PS, Ciconelli RM, Ferraz MB, Martini LA Nutrient intakes related to osteoporotic fractures in men and women--the Brazilian Osteoporosis Study (BRAZOS). Nutr J 2009; Jan298–6


Farrin N, Ostadrahimi AR, Mahboob SA, Kolahi S, Ghavami M Dietary intake and serum bone related chemistry and their correlations in postmenopausal Iranian women. Saudi Med J 2008; Nov29111643–8


Tranquilli AL, Lucino E, Garzetti GG, Romanini C ‘Calcium, phosphorus and magnesium intakes correlate with bone mineral content in postmenopausal women’. Gynecol Endocrinol 1994; 8155–8


Ito S, Ishida H, Uenishi K, Murakami K, Sasaki S The relationship between habitual dietary phosphorus and calcium intake, and bone mineral density in young Japanese women: a cross-sectional study. Asia Pac J Clin Nutr 2011; 203411–7


Kemi VE, Karkkainen MU, Lamberg-Allardt CJ ‘High phosphorus intakes acutely and negatively affect Ca and bone metabolism in a dose-dependent manner in healthy young females’. Br J Nutr 2006; 963545–52


Whybro A, Jagger H, Barker M, Eastell R ‘Phosphate supplementation in young men: lack of effect on calcium homeostasis and bone turnover’. Eur J Clin Nutr 1998; 52129–33


Kemi VE, Kärkkäinen MU, Karp HJ, Laitinen KA, Lamberg-Allardt CJ Increased calcium intake does not completely counteract the effects of increased phosphorus intake on bone: an acute dose-response study in healthy females. Br J Nutr 2008; Apr994832–9


Koshihara M, Katsumata S, Uehara M, Suzuki K Effects of dietary phosphorus intake on bone mineralization and calcium absorption in adult female rats. Biosci Biotechnol Biochem 2005; May6951025–8


Bonjour JP, Gueguen L, Palacios C, Shearer MJ, Weaver CM ‘Minerals and vitamins in bone health: the potential value of dietary enhancement’. British Journal of Nutrition 2009; 101: 1581–1596


Nieves JW ‘Osteoporosis: the role of micronutrients’. Am J Clin Nutr 2005; 8151232S–1239S


Hardwick LL, Jones MR, Brautbar N, Lee DB ‘Magnesium absorption: mechanisms and the influence of vitamin D, calcium and phosphate’. J Nutr 1991; 121113–23


Hruby A, O'Donnell CJ, Jacques PF, Meigs JB, Hoffmann U, McKeown NM Magnesium intake is inversely associated with coronary artery calcification: the framingham heart study. JACC Cardiovasc Imaging 2014; Jan7159–69


Hoorn EJ, Zietse R Disorders of calcium and magnesium balance: a physiology-based approach. Pediatr Nephrol 2013; 28: 1195–1206


Ishimura E, Okuno S, Kitatani K, Tsuchida T, Yamakawa T, Shioi A, Inaba M, Nishizawa Y Significant association between the presence of peripheral vascular calcification and lower serum magnesium in hemodialysis patients. Clin Nephrol 2007; Oct684222–7


Meema HE, Oreopoulos DG, Rapoport A Serum magnesium level and arterial calcification in end-stage renal disease. Kidney Int 1987; Sep323388–94


Tzanakis I, Virvidakis K, Tsomi A, Mantakas E, Girousis N, Karefyllakis N et al Intra and extracellular magnesium levels and atheromatosis in haemodialysis patients. Magnes Res 2004; 172102–8


Salem S, Bruck H, Bahlmann FH, Peter M, Passlick-Deetjen J, Kretschmer A, Steppan S, Volsek M, Kribben A, Nierhaus M, Jankowski V, Zidek W, Jankowski J Relationship between magnesium and clinical biomarkers on inhibition of vascular calcification. Am J Nephrol 2012; 35131–9


Zimmermann P, Weiss U, Classen HG, Wendt B, Epple A, Zollner H, Temmel W, Weger M, Porta S The impact of diets with different magnesium contents on magnesium and calcium in serum and tissues of the rat. Life Sci 2000; Jul14678949–58


Planells E, Llopis J Perán F, Aranda P. Changes in tissue calcium and phosphorus content and plasma concentrations of parathyroid hormone and calcitonin after long-term magnesium deficiency in rats. J Am Coll Nutr 1995; Jun143292–8


van den Broek FA, Beynen AC The influence of dietary phosphorus and magnesium concentrations on the calcium content of heart and kidneys of DBA/2 and NMRI mice. Lab Anim 1998; Oct324483–91


Rayssiguier Y Role of magnesium and potassium in the pathogenesis of arteriosclerosis. Magnesium 1984; 34-6226–38


Takeda R, Nakamura T Effects of high magnesium intake on bone mineral status and lipid metabolism in rats. J Nutr Sci Vitaminol (Tokyo) 2008; Feb54166–75


Mortazavi M, Moeinzadeh F, Saadatnia M, Shahidi S, McGee JC, Minagar A ‘Effect of magnesium supplementation on carotid intima-media thickness and flow-mediated dilatation among hemodialysis patients: a double-blind, randomised, placebo-controlled trial’. Eur Neurol 2013; 695309–16


Pen JX, Li L, Wang X, Zhang YH, Li XF, Wu SY The effect of the magnesium supplementation on vascular calcification in rats. Zhongguo Ying Yong Sheng Li Xue Za Zhi 2012; Jan28120–3


Nagase N, Saijo Y, Nitta H, Tamura Y, Orino S, Akaike Y, Mori H Myocardial disorders caused by magnesium deficiency in diabetic KK mice. Magnesium 1989; 85-6307–15


Reginster JY, Strause L, Deroisy R, Lecart MP, Saltman P, Franchimont P Preliminary report of decreased serum magnesium in postmenopausal osteoporosis. Magnesium 1989; 82106–9


Orchard TS, Larson JC, Alghothani N, Bout-Tabaku S, Cauley JA, Chen Z, Lacroix AZ, Wactawski-Wende J, Jackson RD Magnesium intake, bone mineral density, and fractures: results from the Women’s Health Initiative Observational Study. Am J Clin Nutr 2014; Apr994926–33


Tucker KL, Hannan MT, Chen H, Cupples LA, Wilson PW, Kiel DP ‘Potassium, magnesium and fruit and vegetable intakes are associated with greater bone mineral density in elderly men and women’. Am J Clin Nutr 1999; 694727–36


Ryder KM, Shorr RI, Bush AJ, Kritchevsky SB, Harris T, Stone K et al ‘Magnesium intake from food and supplements is associated with bone mineral density in healthy older white subjects’. J Am Geriatr Soc 2005; 53111875–80


Macdonald HM, New SA, Golden MH, Campbell MK, Reid DM ‘Nutritional associations with bone loss during the menopausal transition: evidence of a beneficial effect of calcium, alcohol and fruit and vegetable nutrients and of a detrimental effect of fatty acids’. Am J Clin Nutr 2004; 791155–65


Kim MH, Yeon JY, Choi MK, Bae YJ Evaluation of magnesium intake and its relation with bone quality in healthy young Korean women. Biol Trace Elem Res 2011; Dec1441-3109–17


Yaegashi Y, Onoda T, Tanno K, Kuribayashi T, Sakata K, Orimo H ‘Association of hip fracture incidence and intake of calcium, magnesium, vitamin D and vitamin K’. Eur J Epidemiol 2008; 233219–25


Saito N, Tabata N, Saito S, Andou Y, Onaga Y, Iwamitsu A, Sakamoto M, Hori T, Sayama H, Kawakita T Bone mineral density, serum albumin and serum magnesium. J Am Coll Nutr 2004; Dec236701S–3S


Aydin H, Deyneli O, Yavuz D Gözü H, Mutlu N, Kaygusuz I, Akalin S. Short-term oral magnesium supplementation suppresses bone turnover in postmenopausal osteoporotic women. Biol Trace Elem Res 2010; Feb1332136–43


Doyle L, Flynn A, Cashman K The effect of magnesium supplementation on biochemical markers of bone metabolism or blood pressure in healthy young adult females. Eur J Clin Nutr 1999; Apr534255–61


Stendig-Lindberg G, Tepper R, Leichter I ‘Trabecular bone density in a two year controlled trial of peroral magnesium in osteoporosis’. Magnes Res 1993; 62155–63


Abraham GE, Grewal H ‘A total dietary program emphasising magnesium instead of calcium. Effect on the mineral density of calcaneous bone in postmenopausal women on hormonal therapy’. J Reprod Med 1990; 355503–7


Turner AG, Hanrath MA, Morris HA, Atkins GJ, Anderson PH The local production of 1,25(OH)2D3 promotes osteoblast and osteocyte maturation. J Steroid Biochem Mol Biol 2013; Oct12


Leiben L, Masuyama R, Torrekens S, Van Looveren R, Schrooten J, Baatsen P et al ‘Normocalcemia is maintained in mice under conditions of calcium malabsorption by vitamin D-induced inhibition of bone mineralisation’. J Clin Invest 2012; 12251803–15


Lips P Interaction between vitamin D and calcium’. Scand J Clin Lab Invest Suppl 2012; 243: 60–4


Heaney RP, Carey R, Harkness L ‘Roles of vitamin D, n-3 polyunsaturated fatty acid and soy isoflavones in bone health’. J Am Diet Assoc 2005; 105111700–2


Lamberg-Allardt C ‘Vitamin D in foods and as supplements’. Prog Biophys Mol Biol 2006; 92133–8


Rafferty K, Heaney RP ‘Nutrient effects on the calcium economy: emphasising the potassium controversy’. J Nutr 2008; 138: 166S–171S


Adamczyk A, Stolarz-Skrzypek K, Wesołowska A, Czarnecka D, Vitamin D, Vitamin D Receptor Activators in Treatment of Hypertension and Cardiovascular Disease. Cardiovasc Hematol Disord Drug Targets 2014; Feb28[Epub ahead of print]


Kang YH, Jin JS, Yi DW, Son SM Bone morphogenetic protein-7 inhibits vascular calcification induced by high vitamin D in mice. Tohoku J Exp Med 2010; Aug2214299–307


Tang FT, Chen SR, Wu XQ, Wang TQ, Chen JW, Li J, Bao LP, Huang HQ, Liu PQ Hypercholesterolemia accelerates vascular calcification induced by excessive vitamin D via oxidative stress. Calcif Tissue Int 2006; Nov795326–39


Ellam T, Hameed A, Ul Haque R, Muthana M, Wilkie M, Francis SE, Chico TJ Vitamin d deficiency and exogenous vitamin d excess similarly increase diffuse atherosclerotic calcification in apolipoprotein e knockout mice. PLoS One 2014; Feb199(2)e88767


Schmidt N, Brandsch C, Kühne H, Thiele A, Hirche F, Stangl GI, Vitamin D receptor deficiency and low vitamin D diet stimulate aortic calcification and osteogenic key factor expression in mice. PLoS One 2012; 7(4)e35316


Schmidt N, Brandsch C, Schutkowski A, Hirche F, Stangl GI Dietary Vitamin D Inadequacy Accelerates Calcification and Osteoblast-Like Cell Formation in the Vascular System of LDL Receptor Knockout and Wild Type Mice. J Nutr 2014; May1445638–46


de Boer IH, Kestenbaum B, Shoben AB, Michos ED, Sarnak MJ, Siscovick DS 25-hydroxyvitamin D levels inversely associate with risk for developing coronary artery calcification. J Am Soc Nephrol 2009; Aug2081805–12


Michos ED, Streeten EA, Ryan KA, Rampersaud E, Peyser PA, Bielak LF, Shuldiner AR, Mitchell BD, Post W Serum 25-hydroxyvitamin d levels are not associated with subclinical vascular disease or C-reactive protein in the old order amish. Calcif Tissue Int 2009; Mar843195–202


Walker MD, Cong E, Kepley A, Di Tullio MR, Rundek T, Homma S, Lee JA, Liu R, Young P, Zhang C, McMahon DJ, Silverberg SJ Association between serum 25-hydroxyvitamin d level and subclinical cardiovascular disease in primary hyperparathyroidism. J Clin Endocrinol Metab 2014; Feb992671–80


Linhartová K, Veselka J, Sterbáková G, Racek J, Topolcan O, Cerbák R Parathyroid hormone and vitamin D levels are independently associated with calcific aortic stenosis. Circ J 2008; Feb722245–50


Sahin I, Okuyan E, Ungör B, Kaya A, Avcı II, Biter HI, Cetin S, Enhos A, Avsar M, Dinçkal MH, Lower vitamin D level is associated with poor coronary collateral circulation. Scand Cardiovasc J 2014; Jun30: 1–19[Epub ahead of print]


Lee SY, Kim HY, Gu SW, Kim HJ, Yang DH 25-hydroxyvitamin D levels and vascular calcification in predialysis and dialysis patients with chronic kidney disease. Kidney Blood Press Res 2012; 355349–54


Young KA, Snell-Bergeon JK, Naik RG, Hokanson JE, Tarullo D, Gottlieb PA, Garg SK, Rewers M Vitamin D deficiency and coronary artery calcification in subjects with type 1 diabetes. Diabetes Care 2011; Feb342454–8


Dishmon DA, Dotson JL, Munir A, Nelson MD, Bhattacharya SK, D Cruz IA, Davis RC, Weber KT Hypovitaminosis D and valvular calcification in patients with dilated cardiomyopathy. Am J Med Sci 2009; May3375312–6


Arad Y, Spadaro LA, Roth M, Scordo J, Goodman K, Sherman S, Lerner G, Newstein D, Guerci AD Serum concentration of calcium, 1,25 vitamin D and parathyroid hormone are not correlated with coronary calcifications. An electron beam computed tomography study. Coron Artery Dis


Watson KE, Abrolat ML, Malone LL, Hoeg JM, Doherty T, Detrano R, Demer LL Active serum vitamin D levels are inversely correlated with coronary calcification. Circulation 1997; Sep169661755–60


Yokoyama K Study on vascular calcification in patients on continuous ambulatory peritoneal dialysis (CAPD): special reference to active vitamin D (VD) treatment. Nihon Jinzo Gakkai Shi 1993; Oct35101171–80


Dalbeni A, Scaturro G, Degan M, Minuz P, Delva P Effects of six months of vitamin D supplementation in patients with heart failure: A randomized double-blind controlled trial. Nutr Metab Cardiovasc Dis 2014; Mar5[Epub ahead of print]


Manson JE, Allison MA, Carr JJ, Langer RD, Cochrane BB, Hendrix SL, Hsia J, Hunt JR, Lewis CE, Margolis KL, Robinson JG, Rodabough RJ, Thomas AM Women’s Health Initiative and Women’s Health Initiative Coronary Artery Calcium Study Investigators. Calcium/vitamin D supplementation and coronary artery calcification in the Women’s Health Initiative. Menopause 2010; Jul174683–91


Hsia J, Heiss G, Ren H, Allison M, Dolan NC, Greenland P, Heckbert SR, Johnson KC, Manson JE, Sidney S, Trevisan M Women’s Health Initiative Investigators. Calcium/vitamin D supplementation and cardiovascular events. Circulation 2007; Feb201157846–54


Schnatz PF, Jiang X, Vila-Wright S, Aragaki AK, Nudy M, O'Sullivan DM, Jackson R, Leblanc E, Robinson JG, Shikany JM, Womack CR, Martin LW, Neuhouser ML, Vitolins MZ, Song Y, Kritchevsky S, Manson JE Calcium/vitamin D supplementation, serum 25-hydroxyvitamin D concentrations, and cholesterol profiles in the Women’s Health Initiative calcium/vitamin D randomized trial. Menopause. 2014; Mar3[Epub ahead of print]


Elamin MB, Abu Elnour NO, Elamin KB, Fatourechi MM, Alkatib AA, Almandoz JP, Liu H, Lane MA, Mullan RJ, Hazem A, Erwin PJ, Hensrud DD, Murad MH, Montori VM Vitamin D and cardiovascular outcomes: a systematic review and meta-analysis. J Clin Endocrinol Metab 2011; Jul9671931–42


Zheng Y, Zhu J, Zhou M, Cui L, Yao W, Liu Y Meta-analysis of long-term vitamin D supplementation on overall mortality. PLoS One 2013; Dec38(12)e82109


Nakamura K, Iki M Efficacy of optimization of vitamin D in preventing osteoporosis and osteoporotic fractures: A systematic review. Environ Health Prev Med 2006; Jul114155–70


Snellman G, Byberg L, Lemming EW, Melhus H, Gedeborg R, Mallmin H, Wolk A, Michaëlsson K Long-term dietary vitamin D intake and risk of fracture and osteoporosis: a longitudinal cohort study of Swedish middle-aged and elderly women. J Clin Endocrinol Metab 2013; [Epub ahead of print]


Bergink AP, Uitterlinden AG, Van Leeuwen JP, Buurman CJ, Hofman A, Verhaar JA, Pols HA Vitamin D status, bone mineral density, and the development of radiographic osteoarthritis of the knee: The Rotterdam Study. J Clin Rheumatol 2009; Aug155230–7


Cranney A, Horsley T, O'Donnell S, Weiler H, Puil L, Ooi D et al ‘Effectiveness and safety of vitamin D in relation to bone health’. Evid Rep Technol Assess 2007; 158: 1–235


Rizzoli R, Boonen S, Brandi ML, Bruyère O, Cooper C, Kanis JA, Kaufman JM, Ringe JD, Weryha G, Reginster JY Vitamin D supplementation in elderly or postmenopausal women: a 2013 update of the 2008 recommendations from the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO). Curr Med Res Opin 2013; Apr294305–13


Joo NS, Dawson-Hughes B, Kim YS, Oh K, Yeum KJ ‘Impact of calcium and vitamin D insufficiencies on serum parathyroid hormone and bone mineral density: analysis of the fourth and fifth Korea National Health and Nutrition Examination Survey (KNHANES IV-3, 2009 and KNHANES V-1, 2010)’. J Bone Miner Res 2013; 28(4)764–70


Min Kim K, Hee Choi S, Lim S, Hoon Moon J, Hee Kim J, Wan Kim S, Chul Jang H, Soo Shin C Interactions between Dietary Calcium Intake and Bone Mineral Density or Bone Geometry in a Low Calcium Intake Population (KNHANES IV 2008-2010). J Clin Endocrinol Metab 2014; [Epub ahead of print]


Cauley JA, Danielson ME, Boudreau R, Barbour KE, Horwitz MJ, Bauer DC, Ensrud KE, Manson JE, Wactawski-Wende J, Shikany JM, Jackson RD ‘Serum 25-hydroxyvitamin D and clinical fracture risk in a multiethnic cohort of women: the Women’s Health Initiative (WHI)’. J Bone Miner Res 2011; Oct26102378–88


Bischoff-Ferrari HA, Dietrich T, Orav J, Dawson-Hughes B ‘Positive association between 25-hydroxy vitamin D levels and bone mineral density: a population-based study of younger and older adults’. Am J Med 2004; 116: 634–8


Zhou W, Langsetmo L, Berger C, Poliquin S, Kreiger N, Barr SI, Kaiser SM, Josse RG, Prior JC, Towheed TE, Anastassiades T, Davison KS, Kovacs CS, Hanley DA, Papadimitropoulos EA, Goltzman D CaMos Research Group. Longitudinal changes in calcium and vitamin D intakes and relationship to bone mineral density in a prospective population-based study: the Canadian Multicentre Osteoporosis Study (CaMos). J Musculoskelet Neuronal Interact 2013; Dec134470–9


Lee AM, Sawyer RK, Moore AJ, Morris HA, O'Loughlin PD, Anderson PH Adequate dietary vitamin D and calcium are both required to reduce bone turnover and increased bone mineral volume. J Steroid Biochem Mol Biol 2013; Dec2[Epub ahead of print]


Avenell A, Mak JC, O'Connell D Vitamin D and vitamin D analogues for preventing fractures in post-menopausal women and older men. Cochrane Database Syst Rev 2014; Apr144: CD000227


Lamberg-Allardt C, Brustad M, Meyer HE, Steingrimsdottir L Vitamin D - a systematic literature review for the 5th edition of the Nordic Nutrition Recommendations. Food Nutr Res 2013; Oct357:


Bolland MJ, Grey A, Gamble GD, Reid IR The effect of vitamin D supplementation on skeletal, vascular, or cancer outcomes: a trial sequential meta-analysis. Lancet Diabetes Endocrinol 2014; Apr24307–20


Poole CD, Smith JC, Davies JS The short-term impact of vitamin D-based hip fracture prevention in older adults in the United Kingdom. J Endocrinol Invest 2014; Jun24[Epub ahead of print]


Lappe JM, Heaney RP ‘Why randomised controlled trials of calcium and vitamin D sometimes fail’. Dermato-Endocrinology 2012; 4295–100


Bonjour JP ‘Calcium and phosphate: a duet of ions playing for bone health’. J Am Coll Nutr 2011; 30: (5 Suppl 1)–438S48


Rao GN Diet and kidney diseases in rats. Toxicol Pathol 2002; NovDec306651–6


Hong H, Kim EK, Lee JS Effects of calcium intake, milk and dairy product intake, and blood vitamin D level on osteoporosis risk in Korean adults: analysis of the 2008 and 2009 Korea National Health and Nutrition Examination Survey. Nutr Res Pract 2013; Oct75409–17


Uenishi K Phosphorus intake and bone health. Clin Calcium 2009; Dec19121822–8


Brot C, Jorgensen N, Madsen OR, Jensen LB, Sorensen OH ‘Relationships between bone mineral density, serum vitamin D metabolites and calcium:phosphorus intake in healthy perimenopausal women’. J Intern Med 1999; 2455509–16


Fenton TR, Lyon AW, Eliasziw M, Tough SC, Hanley DA ‘Phosphate decreases urine calcium and increases calcium balance: a meta-analysis of the osteoporosis acid-ash diet hypothesis’. Nutr J 2009; 8: 41


Boskey AL, Rimnac CM, Bansal M, Federman M, Lian J, Boyan BD ‘Effect of short-term hypomagnesemia on the chemical and mechanical properties of rat bone’. J Orthop Res 1992; 106774–83


Rude RK, Gruber HE, Wei LY, Frausto A, Mills BG ‘Magnesium deficiency: effect on bone and mineral metabolism in the mouse’. Calcif Tissue Int 2003; 72132–41


Bertinato J, Lavergne C, Plouffe LJ, El Niaj HA Small increases in dietary calcium above normal requirements exacerbate magnesium deficiency in rats fed a low magnesium diet. Magnes Res 2014 Jan-Mar; 27135–47


Bae YJ, Kim MH The effects of Mg supplementation in diets with different calcium levels on the bone status and bone metabolism in growing female rats. Biol Trace Elem Res 2013; Dec1553431–8


Rude RK, Singer FR, Gruber HE ‘Skeletal and hormonal effects of magnesium deficiency’. J Am Coll Nutr 2009; 282131–41


Cashman KD, Flynn A ‘Optimal nutrition: calcium, magnesium and phosphorus’. Proc Nutr Soc 1999; 58: 477–87


Horl WH ‘The clinical consequences of secondary hyperparathyroidism: focus on clinical outcomes’. Nephrol Dial Transplant 2004; 19: (Suppl 5)v2–v8


Stubbs J, Liu S, Quarles LD Role of fibroblast growth factor 23 in phosphate homeostasis and pathogenesis of disordered mineral metabolism in chronic kidney disease. Semin Dial 2007; Jul-Aug204302–8


Lips P, Bouillon R, van Schoor NM, Vanderschueren D, Verschueren S, Kuchuk N et al ‘Reducing fracture risk with calcium and vitamin D’. Clin Endocrinol 2010; 73: 277–85


Genuis SJ, Schwalfenberg GK ‘Picking a bone with contemporary osteoporosis management: Nutrient strategies to enhance skeletal integrity’. Clin Nutr 2007; 26: 193–207


Wang M, Li H, You L, Yu X, Zhang M, Zhu R, Hao C, Zhang Z, Chen J Association of serum phosphorus variability with coronary artery calcification among hemodialysis patients. PLoS One 2014; Apr1894e93360


Kestenbaum B, Sachs MC, Hoofnagle AN, Siscovick DS, Ix JH, Robinson Cohen C, Lima JA, Polak JF, Blondon M, Ruzinski J, Rock D, de Boer IH Fibroblast Growth Factor-23 and Cardiovascular Disease in the General Population: The Multi-Ethnic Study of Atherosclerosis. Circ Heart Fail 2014; Mar25[Epub ahead of print]


Palacios C The role of nutrients in bone health, from A to Z. Crit Rev Food Sci Nutr 2006; 46: 621–628

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