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.

Small bowel resection in the rat: the effect upon bone and mineral metabolism.

BACKGROUND AND AIMS: We analyzed bone and mineral metabolism after long-segment small bowel resection in the rat to detect functional and morphological alterations and to determine the development of osteopathy. METHODS: Twelve-week-old male Lewis rats were randomized into short (8-week) or long (16-week) follow-up groups. Sham operation, resection of the proximal third of the small bowel, resection of the distal third of the bowel and resection of the entire jejunum and ileum were carried out. Nineteen days before the end of the experiment the animals were transferred into a metabolic cage to analyze weight gain/loss, food intake, and fecal excretion/24 h. At the end of the experiment the animals were killed; blood samples and bowel and bone specimens were collected, length, weight, volume, density, mineral content, and fracturing energy were determined, and bone histology was examined. The calcium/phosphorus ratio, nonmineralized tissue content and the ratio fracturing energy/mean bone density were calculated. RESULTS: After 8 weeks there were significant differences to the control group in body weight, weight gain, food efficiency, femur length, weight, volume, mineral content, mineral density, fracturing energy per bone volume, and bone density but not in bone calcium or magnesium. After 16 weeks there were differences in body weight, weight gain, food efficiency, femur length, weight, volume, bone mineral content and density, bone minerals, and nonmineralized tissue but not in fracturing energy; the average values of all these parameters were lower in the resected groups, and lowest in the group after resection of the entire jejunum and ileum. Bone histology showed a reduction in trabecular bone mass after long-segment small bowel resection. CONCLUSIONS: Long-segment small bowel resection causes a significant loss of body weight despite of a comparable mean chow ingestion resulting in a significant decreased food efficiency. We conclude that there is no inverse relationship of bone calcium content and the fracture risk, and that there is no severe mineralization defect after long-segment small bowel resection.

High insulin and low IGF-I plasma levels following pancreas transplantation in rats. Implications for bone and mineral metabolism.

Primary disturbances in mineral metabolism and deficiencies in insulin and insulin-like growth factor-I (IGF-I) have been implicated in the pathogenesis of diabetic osteopenia. This prompted us to investigate whether normal bone minerals and bone morphology are preserved after pancreas transplantation. To this end, 8 inbred rats (transplants) were compared with 9 sham-operated rats (controls) 20 months after orthotopic pancreas transplantation. While basal levels of insulin remained unaffected by transplantation, an oral glucose load elicited hyperinsulinemia (integrated incremental response: mean +/- SEM, 62+/-8 nmol l(-1) 60 min in transplants vs. 32+/-6 nmol l(-1) 60 min in controls; p<0.01) in the presence of normal glucose levels. Fecal and urinary excretion and fractional intestinal absorption of calcium, magnesium and phosphorus, net calcium absorption and the respective serum mineral levels were unchanged after transplantation, as were those of the calciotropic hormones. Serum osteocalcin and bone alkaline phosphatase remained unaffected, and urinary excretion of pyridinium and deoxypyridinium were unchanged. Fasting plasma IGF-I concentration was significantly decreased in transplants (930+/-42 ng ml(-1)) vs. control rats (1074+/-49 ng ml(-1); p < 0.05). Despite similar physical and chemical properties of bone in both groups, histomorphometry revealed slight osteopenia in transplant rats, as reflected by a 38% reduction in the cancellous bone area of the proximal tibial metaphysis. Plasma IGF-I levels were significantly correlated with bone mineral apposition rate (r=0.70, p<0.02), osteoblast perimeter (r=0.60, p<0.05) and osteoid perimeter (r=0.60, p<0.05). In conclusion, pancreas transplantation preserves physical and chemical properties of bone, but bone metabolism is not completely normal after transplantation, as evidenced by decreased cancellous bone. This might have resulted from the insulin resistance associated with the lowering of the plasma IGF-I level, which was correlated with the mineral apposition rate.