Drug-Induced Bone Disease Part 3

Agents That Impair Absorption of Calcium

Medications that impair the absorption of calcium can have a negative impact on serum calcium levels. The malabsorption of calcium has been documented in patients receiving colchicine, mineral oil, or sodium sulfonated polystyrene resin. Similarly, agents known to enhance the renal excretion of calcium — such as loop diuretics — also predispose patients to hypocalcemia.

Magnesium Depletion: In addition to medications that directly alter serum calcium levels, agents that deplete the body of magnesium ultimately cause hypocalcemia. In fact, drug-induced hypocalcemia is often due to a depletion of magnesium stores. Magnesium deficiency can induce a transient hypoparathyroidism by reducing the secretion of parathyroid hormone (PTH) and a blunted PTH response. This result is an inhibition of the hypocalcemic feedback loop. Other agents that suppress PTH secretion — with resulting inhibition of the hypocalcemic feedback loop — include aluminum salts and excessive alcohol.

Cisplatin, Aminoglycosides, Cyclosporine: Cisplatin, aminoglycosides, and cyclosporine are known to increase magnesium wasting through a variety of mechanisms. Cisplatin-induced hypomagnesemia is dependent on dose and duration of therapy. Cisplatin induces hypomagnesemia by causing direct injury to the mechanisms of magnesium reabsorption in the ascending limb of the loop of Henle and the distal tubule. Forastiere and colleagues reported that the total exposure of free platinum contributes to direct injury and renal toxicity. Mavichak, et al. have also suggested that cisplatin causes lesions in the distal renal tubules responsible for renal magnesium losses. Carboplatin, an antineoplastic agent with a chemical structure similar to cisplatin, has been reported to have a lower incidence of hypomagnesemia.

Renal wasting of magnesium is also fairly common in patients receiving prolonged, high doses of aminoglycosides. Aminoglycosides can inhibit the proximal tubular transport of magnesium in the kidney, predisposing patients with poor magnesium intake to lower magnesium levels. Transplant patients receiving cyclosporine also may experience severe hypomagnesemia due to increased urinary excretion of magnesium.Table 2 lists agents known induce hypocalcemia by depleting magnesium stores. Treatment for hypocalcemia induced by hypomagnesemia involves correcting hypomagnesemia first, then managing serum calcium levels.