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Growth failure and decreased bone mineral of newborn rats with chronic furosemide therapy
Insights
Chronic furosemide treatment in newborn rats caused growth delay and increased urinary calcium and magnesium loss. Bone mineral content decreased proportionally with growth, but bone density remained unchanged.
Area of Science:
- Pharmacology
- Pediatric Nephrology
- Developmental Biology
Background:
- Furosemide is a diuretic commonly used in neonates.
- Potential impact of furosemide on bone mineral metabolism in developing animals is not fully understood.
Purpose of the Study:
- To investigate the effects of chronic furosemide administration on bone mineral content (calcium and magnesium) in newborn Sprague-Dawley rats.
Main Methods:
- Newborn Sprague-Dawley rat pups were assigned to control, low-dose (5 mg/kg/day), or high-dose (15 mg/kg/day) furosemide groups.
- Treatment occurred from postnatal days 4 to 28.
- Bone mineral content (calcium, magnesium, phosphorus) and urinary mineral concentrations were measured at sacrifice.
Main Results:
- Furosemide treatment resulted in dose-dependent growth delay.
- Increased urinary calcium and magnesium concentrations were observed in treated pups.
- Total bone calcium and magnesium were reduced in furosemide-treated pups, correlating with growth retardation.
Conclusions:
- Chronic furosemide therapy in newborn rats leads to impaired growth and increased urinary calcium and magnesium excretion.
- While total bone mineral content decreased, the mineral content per unit of bone dry weight was not significantly affected, suggesting the primary impact is on overall growth rather than bone mineralization density.
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.