MAGNESIUM-DEFICIENCY INDUCES BONE LOSS IN THE RAT

Disorders in which magnesium (Mg) depletion is common have an associat ed high incidence of osteoporosis, Mg depletion in humans results in h ypocalcemia, low serum parathyroid hormone (PTH) and 1,25(OH)(2)-vitam in D levels, as well as PTH and vitamin D resistance which may serve a s mechanisms for the development of osteoporosis, In order to determin e if isolated Mg depletion will result in bone loss, we have induced d ietary Mg deficiency in the rat. Adult (290 g) female rats were given either a low-Mg diet (2 mg/100 g chow; n = 6) or a normal control Mg d iet (63 mg/100 g chow n = 6). Dietary calcium (Ca) was normal in both groups (592 mg/100 g chow). At 12 weeks, blood was obtained for serum Mg, Ca, PTH, 1,25(OH)(2)-vitamin D, and osteocalcin determinations. Th e rats were then euthanized and the femurs obtained for mineral analys is and histomorphometry. Serum Mg in the low-Mg group was less than co ntrol(0.4 +/- 0.2 vs. 1.9 +/- 0.2 mg/dl, p < 0.001; mean +/- SD) while serum Ca was higher(11.7 +/- 0.5 vs. 9.3 +/- 0.4 mg/dl, p < 0.001). P TH was suppressed in the Mg-deficient group (36 +/- 16 vs. 109 +/- 30 pg/ml in controls, p < 0.002), Serum 1,25(OH)2-vitamin D was also supp ressed in the Mg-deficient animals(7.1 +/- 4.8 vs. 28.5 +/- 8.2 pg/ml in controls, p < 0.002). Serum osteocalcin levels were not different ( 19.8 +/- 2.5 ng/ml in Mg-deficient rats vs. 15.3 +/- 3.4 ng/ml in cont rols). While the ash weight of Ca and phosphorus in the femur did not change, the ash weight of Mg fell (low-Mg group 0.55 +/- 0.01 %: contr ols 0.65 +/- 0.02 %, p < 0.001). Histomorphometry demonstrated reducti on in bone mass the trabecular bone volume in the femur of the low-Mg group was reduced from control (7.7 +/- 0.2 vs. 13.7 +/- 1.9 %, p < 0. 002). A surprising new observation was an increase in osteoclast (OC) bone resorption with Mg depletion. The number of OC per millimeter bon e surface was 16.9 +/- 1.3 in the low-Mg group versus 7.8 +/- 1.5 in c ontrols (p < 0.001). The percentage of bone surface occupied by OC was 38.3 +/- 3.7 in the low-Mg group versus 17.7 +/- 2.4 in controls (p < 0.001). This increased resorption occurred with an inappropriate non- altered bone-forming surface relative to control (% osteoid surface: l ow-Mg group 2.4 +/- 0.7 vs. controls 2.6 +/- 0.4; % osteoid volume: lo w-Mg group 0.25 +/- 0.09 vs, controls 0.38 +/-; 0.06; number of osteob lasts per millimeter bone surface: low-Mg group 0.9 +/- 0.3 vs. contro ls 1.3 +/- 0.3), No increase in bone-forming surface or osteoblast num ber despite an increase in OC-resorbing surface and OC number strongly suggests impaired activation of osteoblasts and an uncoupling of bone formation and bone resorption. Our data demonstrate that Mg depletion in the rat alters bone and mineral metabolism which results in bone l oss.