gms | German Medical Science

Objectives: Hyponatremia (HypoNa) is a common electrolyte disorder in the clinical practice. Its treatment is often failed due to the lack of regular monitoring. However, it can cause or accelerate osteoporosis. One of the most common causes of HypoNa is the syndrome of inappropriate antidiuretic hormone (vasopressin) secretion (SIADH) that can be caused by various diseases, drugs, emotional stress, pain, sport or other reasons. Estrogen deficiency following menopause in women is related to postmenopausal osteoporosis. This study investigated the effect of HypoNa and compared it with estrogen depletion on bone tissue in two respective rat models.

Methods: The SIADH rat model developed by Verbalis et al. (2010, JBMR, 25:554-563) was applied to induce HypoNa in rats by treating them with desmopressin and feeding with liquid rodent diet (BioServ, USA). Desmopressin, a synthetic analogue of vasopressin was infused at a rate 5 ng/h via a subcutaneous implanted osmotic pumps (Alzet, Durect Co., USA). Ovariectomized rats (OVX) were used as a model of postmenopausal osteoporosis. Seven-month old female Sprague Dawley rats were divided into 4 groups (n=6):

1.

ovariectomized rats without pump (OVX-P),

2.

intact rats without pump (Control-P),

3.

intact rats with pumps filled with vehicle (0.9% NaCl) (Control+P),

4.

intact rats implanted with pumps filled with desmopressin (Desmo+P).

The pumps were replaced after 6 weeks. All animals received liquid rodent diet and water without restrictions throughout the experiment. After 12 weeks of treatments, the fourth lumbar vertebral body (L4), tibiae and femora were analyzed by biomechanical, micro-computed tomographical, histological and ashing analyses. A one-way analysis of variance and Tukey test were applied to reveal the differences between the groups (p < 0.05).

Results and conclusion: After 12 weeks, OVX was confirmed by the reduced uterus weight (OVX-P: 0.17+0.04 g; all other groups: 0.69+0.17 g). HypoNa in Desmo+P group was confirmed by low sodium in the serum (Desmo+P: 110+3 mmol/L, all other groups: 141+2 mmol/L). Control-P and Control+P groups did not show detectable differences in any of the parameters studied and therefore a group without pump can possibly be avoided in similar experiments. Compared to Control-P and Control+P groups, most of the bone parameters (bone mineral density, trabecular structure, anorganic content) were similarly decreased both in OVX-P and Desmo+P groups. Biomechanical parameters of femur and tibia were also decreased compared to the controls in OVX-P and Desmo+P groups, whereas in L4 no differences were detected between the groups. The degree and timing of changes in bone after treatments were previously reported to differ between the skeletal sites. This experiment showed that HypoNa can impair bone tissue to a similar extent as an estrogen deficiency, thus demonstrating the importance of managing the balance between water and sodium to prevent osteoporosis.