Reduction of dietary magnesium by only 50% in the rat disrupts bone and mineral metabolism

The objective of this study was to determine the effect of a moderate reduction of dietary magnesium [50% of nutrient requirement (50% NR)] on bone and mineral metabolism in the rat, and to explore possible mechanisms for the resultant reduced bone mass. Female rats were 6 weeks of age at the start of study. Serum magnesium (Mg), calcium (Ca), parathyroid hormone (PTH), 1,25(OH)2-vitamin D, alkaline phosphatase, osteocalcin, and pyridinoline were measured during the study at 3- and 6-month time points in control (dietary Mg of 100% NR) and Mg-deficient animals (dietary Mg at 50% NR). Femurs and tibias were also collected for mineral content analyses, micro-computerized tomography, histomorphometry, and immunohistochemical localization of substance P, TNFα, and IL-1β at 3 and 6 months. Although no significant change in serum Mg was observed, Mg deficiency developed, as assessed by the reduction in bone Mg content at the 3- and 6-month time points (0.69±0.05 and 0.62±0.04% ash, respectively, in the Mg depletion group compared to 0.74±0.04 and 0.67±0.04% ash, respectively, in the control group; p=0.0009). Hypercalcemia did not develop. Although serum Ca level remained in the normal range, it fell significantly with Mg depletion at 3 and 6 months (10.4±0.3 and 9.6±0.3 mg/dl, respectively, compared to 10.5±0.4 and 10.1±0.6 mg/dl, respectively, in the control group; p=0.0076). The fall in serum Ca in the Mg-depleted animals was associated with a fall in serum PTH concentration between 3 and 6 months (603±286 and 505±302 pg/ml, respectively, although it was still higher than the control). The serum 1,25(OH)2-vitamin D level was significantly lower in the Mg depletion group at 6 months (10.6±7.1 pg/ml) than in the control (23.5± 12.7 pg/ml) (p<0.01 by the t-test). In Mg-deficient animals, no difference was noted in markers of bone turnover. Trabecular bone mineral content gain was less over time in the distal femur with Mg deficiency at 3 and 6 months (0.028±0.005 and 0.038±0.007 g, respectively, compared to 0.027±0.004 and 0.048±0.006 g, respectively, in the control group; p<0.005). Histomorphometry at these time points demonstrated decreased trabecular bone volume (15.76±1.93 and 14.19±1.85%, respectively, compared to 19.24±3.10 and 17.30±2.59%, respectively, in the control group; p=0.001). Osteoclast number was also significantly increased with Mg depletion (9.07±1.21 and 13.84±2.06, respectively, compared to 7.02±1.89 and 10.47±1.33, respectively, in the control group; p=0.0003). Relative to the control, immunohistochemical staining intensity of the neurotransmitter substance P and of the cytokines TNFα and IL-1β was increased in cells of the bone microenvironment in the Mg depletion group, suggesting that inflammatory cytokines may contribute to bone loss. These data demonstrate that Mg intake of 50% NR in the rat causes a reduced bone mineral content and reduced volume of the distal femur. These changes may be related to altered PTH and 1,25(OH)2-vitamin D formation or action as well as to an increase release of substance P and the inflammatory cytokines TNFα and IL-1β.