Growth Failure and Decreased Bone Mineral of Newborn Rats with Chronic Furosemide Therapy

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Abstract
To test the hypothesis that chronic furosemide treatment in otherwise healthy newborn animals may lead to lowered bone mineral [calcium (Ca) and magnesium (Mg)] content, healthy littermates within each litter of Sprague-Dawley rat pups were randomly assigned to three groups: control, low dose furosemide (5 mg/kg/day), and high dose furosemide (15 mg/kg/day). The pups were treated between days 4 and 28 postnatally. The wet and dry weights of kidneys and tibiae significantly correlated with body weights at sacrifice. Furosemide-treated pups demonstrated a dose-dependent growth delay, decreased total bone (tibiae) Ca and Mg, increased urine Ca and Mg concentration, and a significant inverse correlation between bone Ca and urine Ca concentration. There was no significant difference among the groups when bone Ca and Mg were normalized to per gram of bone dry weight. There were no significant differences among the groups with respect to bone phosphorus or urinary phosphorus concentration; kidney and serum Ca and Mg; or serum sodium, potassium, alkaline phosphatase and immunoreactive parathyroid hormone concentration. We conclude that chronic furosemide therapy leads to growth failure and to increased urinary losses of Ca and Mg. Total bone Ca and Mg in the furosemide-treated pups were diminished in proportion to growth retardation but the bone mineral content per unit of dry weight remained similar to control pups.