Magnesium Deficiency Induces Bone Loss in the Rat

Abstract

Disorders in which magnesium (Mg) depletion is common have an associated high incidence of osteoporosis. Mg depletion in humans results in hypocalcemia, low serum parathyroid hormone (PTH) and 1,25(OH)₂-vitamin D levels, as well as PTH and vitamin D resistance which may serve as mechanisms for the development of osteoporosis. In order to determine if isolated Mg depletion will result in bone loss, we have induced dietary 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 diet (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. The rats were then euthanized and the femurs obtained for mineral analysis and histomorphometry. Serum Mg in the low-Mg group was less than control (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). PTH 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 suppressed 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 controls). 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%, controls 0.65 ± 0.02%, p < 0.001). Histomorphometry demonstrated reduction 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 bone surface was 16.9 ± 1.3 in the low-Mg group versus 7.8 ± 1.5 in controls (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: low-Mg group 2.4 ± 0.7 vs. controls 2.6 ± 0.4; % osteoid volume: low-Mg group 0.25 ± 0.09 vs. controls 0.38 ± 0.06; number of osteoblasts per millimeter bone surface: low-Mg group 0.9 ± 0.3 vs. controls 1.3 ± 0.3). No increase in bone-forming surface or osteoblast number 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 loss.

Effects of Dietary Calcium Supplementation on Bone Metabolism, Kidney Mineral Concentrations, and Kidney Function in Rats Fed a High-Phosphorus Diet

“…Furthermore, a previous study showed that increased dietary Ca depresses Mg absorption (24). Many studies have shown that Mg deficiency induces bone loss with an increase in bone resorption (25,26). Therefore, it is possible that the combination of a high-P diet and dietary Ca supplementation reduces Mg absorption further.…”

Renal Magnesium Wasting, Hypomagnesemic Hypocalcemia, Hypocalciuria and Osteopenia in a Patient with Glycogenosis Type II

“…Experimental hypomagnesemia in animal models has resulted in impaired bone growth, osteopenia and increased skeletal fragility [39,40]. Hypomagnesemia in humans results in hypocalcemia, low serum PTH and 1,25-dihydroxyvitamin D levels, as well as PTH and vitamin D resistance which may serve as mechanisms for the development of osteoporosis [41]. While the fall in PTH and/or 1,25-dihydroxyvitamin D may explain a decrease in osteoblast activity, the mechanism for increased osteoclast activity is unclear [42].…”

The Relationship between Bone Mineral Density and Dietary Intake in Moroccan Children with Juvenile Idiopathic Arthritis

“…Rude et al tested the effects of deficient diets on bone tissue in rats [31]. The results showed the histology decreased trabecular bone volume, increased osteoclast activity without activation of osteoblasts and biologically hypercalcemia, a decrease in serum parathyroid hormone (PTH) and 1, 25 (OH) vitamin D. Thus, the Mg depletion would lead to bone resorption uncoupled could exert inhibitory effect on PTH.…”

“…In the current study, decreased intake of folate was associated with high BMD. In a study of Rejnmark L. et al, they found that high dietary intake of folate exerts positive effects on BMD [31]. Also, Rivas A. et al showed that the BMD was signifycantly associated with the intake of folate [44].…”