Effects of low medium magnesium concentration on bone resorption in response to parathyroid hormone and 1,25-dihydroxyvitamin D in organ culture.

We have examined the effects of decreasing the magnesium concentration in the medium on bone resorption in organ culture. During a 5-day culture, low magnesium (0.25 vs. 0.8 mM) caused a decrease in unstimulated 45Ca release from live and killed fetal rat bones for the first 2 days but not thereafter, suggesting an early and transient alteration in physicochemical equilibrium for calcium between bone and extracellular fluid in magnesium deficiency. In addition, 45Ca release in response to low and intermediate doses of PTH and 1,25-dihydroxyvitamin D3 was significantly impaired throughout the 5-day culture period, such that the response to the lowest dose of both hormones that was effective at 0.8 mM magnesium was abolished at 0.25 mM. The DNA and magnesium content of bones was significantly decreased after 1 day of preculture in deficient medium. Subsequently, there was DNA loss from control bones, such that there was no significant difference in high and low magnesium concentrations at the end of the culture period. Our studies show that low magnesium concentration impairs the skeletal response to calcium-mobilizing hormones in vitro and that this is not likely to be due to nonspecific cell toxicity. Such an effect may play a role in the hypocalcemia associated with magnesium depletion in vivo.