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The effect of magnesium (Mg) supplementation on bone metabolism has been studied in the normal young mouse. Weanling male mice were given Mg-supplemented drinking water (5 mM or 32 mM Mg) for 4 weeks. Mineral and skeletal changes were assessed by biochemical methods and by histomorphometric analysis of endosteal bone formation and resorption parameters evaluated on tetracycline double-labeled, undecalcified caudal vertebrae. Magnesium supplementation increased serum and urinary Mg concentrations and bone Mg content. Both the calcification rate and the extent of tetracycline double-labeled osteoid surface increased progressively in Mg-treated mice, whereas the mineralization lag time was shortened. The osteoblastic surface was reduced, leading to a fall in osteoid surface. Stimulation of bone mineralization was associated with a rise in extracellular calcium (Ca) and phosphorus (P) concentrations whereas serum 25-OHD and 1,25(OH)2D levels remained normal. The Mg supplementation increased the number of acid phosphatase stained chondroclasts and osteoclasts and the extent of resorbing surface showing histochemically stained osteoclasts. Although urinary OH-proline increased above normal, Ca, P, and cyclic adenylic acid (cAMP) excretion and phosphate concentration (TmP/GFR) remained normal, suggesting that parathyroid hormone (PTH) secretion was not altered. The trabecular bone volume remained normal, showing that the increased bone resorption was balanced by the stimulated bone mineralization. The results show that Mg supplementation influenced both bone formation and resorption in the young mouse, and that the stimulation of bone mineralization was the result of increased extracellular mineral availability.(ABSTRACT TRUNCATED AT 250 WORDS)

The effects of continuous administration of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] on mineral and bone metabolism have been examined in the normal mouse. Four doses (0.05-0.25 micrograms/kg/day) of 1,25(OH)2D3 were infused continuously for 4 weeks in 21-day-old intact animals. Mineral and skeletal changes were evaluated by analytical methods and by histomorphometric analysis of endosteal bone formation and resorption parameters. All doses of 1,25(OH)2D3 increased the fractional osteoclastic surface and the osteoclast number in conjunction with increased hydroxyproline excretion. 1,25(OH)2D3 induced a dose-dependent elevation of the calcification rate, reduction of the mean osteoid seam thickness, and shortening of the mineralization lag time. In addition, there was a dose-related increase in the extent of tetracycline double-labeled osteoid surface and a concurrent rise in the fractional osteoblastic surface associated with elevated serum alkaline phosphatase levels. Increased bone formation appeared to have been balanced by increased bone resorption since the trabecular bone volume remained unchanged. Except at the highest dose given, serum calcium and phosphate concentrations remained normal in spite of increased bone mobilization and presumably enhanced intestinal absorption of minerals. Urinary cAMP and TmP/GFR remained normal, suggesting that parathormone secretion was not altered. The results show that continuous 1,25(OH)2D3 infusion in the young mouse produces a dose-dependent stimulation of bone mineralization rate in response to increased osteoclastic bone resorption. The data indicate that 1,25(OH)2D3 can regulate bone turnover as well as mineral homeostasis in the young mouse.

The hypophosphatemic male mouse (Hyp/y), the proposed model for human vitamin D-resistant rickets (VDRR), is characterized by chronic hypophosphatemia, dwarfism, and rachitic and osteomalacic bone lesions. We have reported that treatment of Hyp/y mice with phosphate salts (Pi) heals rickets but does not correct the defective endosteal bone mineralization. In an attempt to cure osteomalacia, mutant male animals were treated with Pi combined with 25-hydroxyvitamin D3 (25OHD3, 1 microgram/kg/day), 24,25-dihydroxyvitamin D3 [24,25(OH)2D3, 0.5 microgram/kg/day], or 1,25-dihydroxyvitamin D3 [1,25(OH)2D3, 0.05--0.25 microgram/kg/day] infused constantly for 3 weeks. The biochemical and skeletal effects of treatment were assessed by analytical methods and bone histomorphometry. The results show that only 1,25(OH)2D3 produced a dose-dependent elevation of serum calcium and phosphorus, and greatly improved bone mineralization at doses high enough to increase serum calcium and phosphorus concentrations within or above the normal range. Better improvement of bone mineralization was obtained when Pi was combined to 1,25(OH)2D3. In conjunction with the correction of hypocalcemia, Pi + 1,25(OH)2D3 suppressed the stimulation of bone turnover induced by Pi supplementation. The results show that, as in VDRR children, 1,25(OH)2D3 produces beneficial effects on bone lesions in Hyp/y mice, mainly through enhancement of mineral availability. However, the persistence of osteomalacia despite correction of serum mineral concentrations suggests that there is a specific bone cell resistance to mineral and/or hormonal influences in Hyp/y mice.