The syndrome of inappropriate
antidiuretic hormone secretion (
SIADH) is frequently responsible for chronic
hyponatremia in the elderly due to age-related disruption of the inhibitory component of brain osmoregulatory mechanisms. Recent research has indicated that chronic
hyponatremia is associated with gait disturbances, increased falls, and bone fragility in humans, and we have found that chronic
hyponatremia causes increased
bone resorption and reduced bone mineral density in young rats. In this study, we used a model of
SIADH to study multi-organ consequences of chronic
hyponatremia in aged rats. Sustained
hyponatremia for 18 weeks caused progressive reduction of bone mineral density by DXA and decreased
bone ash calcium, phosphate and
sodium contents at the tibia and lumbar vertebrae. Administration of 10-fold higher
vitamin D during the last 8 weeks of the study compensated for the reduction in bone formation and halted bone loss. Hyponatremic rats developed
hypogonadism, as indicated by slightly lower serum
testosterone and higher serum FSH and LH concentrations, markedly decreased testicular weight, and abnormal testicular histology. Aged hyponatremic rats also manifested decreased body fat, skeletal muscle
sarcopenia by densitometry, and
cardiomyopathy manifested as increased heart weight and perivascular and interstitial
fibrosis by histology. These findings are consistent with recent results in cultured osteoclastic cells, indicating that low extracellular
sodium concentrations increased oxidative stress, thereby potentially exacerbating multiple manifestations of senescence. Future prospective studies in patients with
SIADH may indicate whether these multi-organ age-related comorbidities may potentially contribute to the observed increased incidence of fractures and mortality in this population.