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 imp aired bone growth, osteopenia, and increased skeletal fragility. In order t o assess changes in bone and mineral homeostasis that may be responsible, w e 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 ca lcium (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 progressiv ely in the Mg deficient rats to 30 pg/ml by week 16 (control = 96 pg/ml). S erum 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 th e 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 10.74 percent) by 16 weeks. The percent ash weight of po tassium also fell progressively in the Mg deficient group to approximately 30 percent of control by 16 weeks. Histomorphometric analyses showed a sign ificant 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 t he endosteal bone surface features showed significantly greater bone resorp tion 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 occ urred in the presence of an inappropriate lowered bone forming surface rela tive 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 b y osteoid (percent OS/BS = 0.41 vs 2.27 percent in controls) were also note d. Our findings demonstrate a Mg-deficiency induced uncoupling of bone form ation 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 sugg est that Mg deficiency may be a risk factor for osteoporosis.