Magnesium deficiency-induced osteoporosis in the rat: uncoupling of bone formation and bone resorption

Magnesium (Mg) intake has been linked to bone mass and/or rate of bone loss in humans. Experimental Mg deficiency in animal models has resulted in impaired bone growth, osteopenia, and increased skeletal fragility. In order to assess changes in bone and mineral homeostasis that may be responsible, we induced dietary Mg deficiency in adult Simonsen albino rats for 16 weeks. Rats were fed either a low Mg diet (0.002 percent) or a normal control Mg diet (0.063 percent). Blood was obtained at baseline, 4 weeks, 8 weeks, 12 weeks and 16 weeks in both groups for serum Mg, calcium, PTH, and 1.25(OH)2-vitamin D determinations. Femora were harvested at 4 weeks and 16 weeks for mineral analysis and histomorphometry. Serum Mg fell in the Mg depleted group to 0.6 mg/dl (mean) by 16 weeks (controls = 2.0 mg/dl). The serum calcium (Ca) concentration was higher in the Mg depleted animals at 16 weeks, 10.8 mg/dl (controls = 8.9 mg/dl). Serum PTH concentration fell progressively in the Mg deficient rats to 30 pg/ml by week 16 (control = 96 pg/ml). Serum concentration of 1.25(OH)2-vitamin D also fell progressively in the Mg deficient animals by 16 weeks to 14 pg/ml (control = 30 pg/ml). While the percent ash weights of Ca and phosphorus in the femur were not different at any time point, the percent ash weight of Mg progressively fell to 0.54 percent vs control (0.74 percent) by 16 weeks. The percent ash weight of potassium also fell progressively in the Mg deficient group to approximately 30 percent of control by 16 weeks. Histomorphometric analyses showed a significant drop in trabecular bone volume in Mg deficient animals by 16 weeks (percent BV/TV = 13.2 percent vs 17.3 percent in controls). Evaluation of the endosteal bone surface features showed significantly greater bone resorption in the Mg depleted group as reflected in increased number of tartrate-resistant positive osteoclasts/mm bone surface (7.8 vs 4.0 in controls) and an elevated percent of bone surface occupied by osteoclasts (percent OcS/BS = 12.2 percent vs 6.7 percent in controls. This increased resorption occurred in the presence of an inappropriate lowered bone forming surface relative to controls; a decreased number of osteoblasts per mm bone surface (0.23 vs 0.94 in control) and a decrease in percent trabecular surface lined by osteoid (percent OS/BS = 0.41 vs 2.27 percent in controls) were also noted. Our findings demonstrate a Mg-deficiency induced uncoupling of bone formation and bone resorption resulting in a loss of bone mass. While the fall in PTH and/or 1.25(OH)2-D may explain a decrease in osteoblast activity, the mechanism for increased osteoclast activity is unclear. These data suggest that Mg deficiency may be a risk factor for osteoporosis.