Media calcification, low erythrocyte magnesium, altered plasma magnesium, and calcium homeostasis following grafting of the thoracic aorta to the infrarenal aorta in the rat--differential preventive effects of long-term oral magnesium supplementation alone and in combination with alkali.

Calcifications in arterial media are clinically well documented, but the role played by magnesium in pathophysiology and therapy is uncertain. To clarify this, an animal model in which the juxtacardial aorta was grafted to the infrarenal aorta, and the subsequent calcifications in the media of the graft and their response to oral supplementation with three magnesium-containing and alkalinizing preparations was investigated. Groups of highly inbred rats were formed as follows: sham-operation (Sham, n = 12), aorta transplantation (ATx, n = 12), ATx + magnesium citrate (MgC, n = 12), ATx + MgC + potassium citrate (MgCPC, n = 12), ATx + MgC + MgCPC (MgCPCSB, n = 12). At 84 (+/-2) days after ATx with or without treatment the following observations were made: (1) weight gain and general status were normal; (2) ATx rats developed massive media calcification, mineral accumulation in the graft, decreased erythrocyte magnesium and plasma parathyroid hormone, and increased plasma ionized magnesium and calcium, and uric acid; (3) Mg-treated rats developed variable degrees of metabolic alkalosis, but only MgCPCSB supplementation prevented calcifications. Additional findings after ATx alone were: imbalance in endothelin and nitric oxide production, the mineral deposited in media was poorly crystallized calcium phosphate, calcium exchange between plasma and graft, and bone resorption were unchanged. The superior anti-calcification effect of MgCPCSB was characterized by complete restoration of normal extracellular mineral homeostasis and uric acid, but sub-optimal normalization of erythrocyte magnesium. It was concluded that in the rat: (1) ATx causes loss of cellular magnesium, excess of extracellular magnesium and calcium in the presence of apparently unchanged bone resorption, and increased uricemia; (2) ATx facilitates enhanced influx of calcium into vascular tissue, leading to calcium phosphate deposition in the media; (3) ATx-induced calcification is prevented by dietary supplementation with a combination of magnesium, alkali citrate and bases. Although the described circulatory model of media calcification in the rat requires further investigation, the data allow ascribing a fundamental role to magnesium and acid-base metabolism.

Acute oral calcium-sodium citrate load in healthy males. Effects on acid-base and mineral metabolism, oxalate and other risk factors of stone formation in urine.

The currently preferred calcium preparations for supplementation of food vary widely with respect to calcium availability, effects on systemic mineral metabolism, acid-base status, and the calciuria-induced risk of urinary tract stone formation. In eight healthy males we studied the response to an acute load with alkali(sodium)-containing soluble calcium citrate (CSC) (molar ratio calcium/sodium/citrate approx. = 1/1/1), when taken in three different doses (10, 20, 30 mmol calcium) together with a continental breakfast. Intestinal calcium absorption, serum calcium, calcitonin, parathyroid hormone (PTH) other markers of bone metabolism, net acid excretion and calcium oxalate crystallization in urine were evaluated. CSC evoked a dose-dependent increase in calcium absorption, calcium in serum and urine, but no overt hypercalcemia, and calciuria was low relative to the excess calcium ingested; PTH fell and calcitonin rose (p < 0.05 vs. breakfast alone), but the diet-independent markers of bone resorption declined only insignificantly, while the markers of bone formation and turnover remained unchanged. There was a significant "once-daily" effect (= cumulative 24 h postload response) of CSC: a decrease in urinary cyclic AMP, phosphorus, and ammonium, and an increase in urinary bicarbonate. Soon after CSC intake, urinary calcium oxalate and hydroxyapatite supersaturation increased dose-dependently, the calcium oxalate crystal diameter was increased, but crystal aggregation time, which is crucial for stone formation, remained statistically unchanged. Thus, CSC provides calcium in a bioavailable form, creates mild systemic alkalinisation and inhibition of bone resorption, but leaves the risk of developing urinary stones unchanged. Comparative long-term studies on bone growth and the maintenance of bone health, using alkali-containing versus alkali-free calcium citrate, appear worthwhile.