Comparison of the effects of hyponatremia and estrogen depletion on bone tissue in a female rat model

Objectives Postmenopausal osteoporosis is mainly related to estrogen deficiency following menopause in women. However, also other factors including chronic hyponatremia can influence bone tissue. Hyponatremia is a common electrolyte disorder in the clinical practice which is not usually treated, though it is associated with increased risk of falls and fragility fractures. In a recent clinical study, we reported a high prevalence of chronic hyponatremia (>15 %) in patients with fragility fractures. The intention of this study was to compare the effects of hyponatremia and estrogen depletion on bone tissue in a rat model.

Methods Seven-month old female Sprague Dawley rats were divided into 4 groups (n = 6): (1) intact, (2) intact with pumps, 0.9 % NaCl (intact+vehicle), (3) intact with pumps, desmopressin (intact+desmo), (4) ovariectomized rats (Ovx). The method developed by Verbalis et al. (2010, JBMR, 25:554-563) was used to induce hyponatremia in rats. Rats were infused with desmopressin at a rate 5 ng/h via a subcutaneous implanted osmotic pumps (Alzet, Durect Co., USA). Saline solution was used as a vehicle in pumps. Pump implantation and ovariectomy were performed under isoflurane anesthesia. The pumps were replaced after 6 weeks. All animals received liquid rodent diet (BioServ, USA) and water without restrictions throughout the experiment. Fourth lumbar vertebral body and left tibia were analyzed by in-vivo peripheral quantitative computed tomography (pQCT) after 6 and 12 weeks of treatments. Weight of body, internal organs, brain, muscle and uterus was recorded at the end of the study (week 12).

Results and Conclusion In the intact+desmo group, weight of body, heart, kidney and soleus muscle was increased, whereas bone density and area were decreased significantly compared with intact and intact+vehicle groups. In the Ovx group, weight of visceral fat and body was higher, whereas uterus weight and bone parameters were lower than in intact and intact+vehicle groups. After 6 weeks, a detrimental effect of hyponatremia on bone was stronger than the Ovx effect. After 12 weeks, bone quality was at a comparable low level in both groups. Differences between intact and intact+vehicle groups were not detected in any parameter studied. Hyponatremia induced osteoporosis developed earlier than osteoporosis induced by estrogen deficiency. Further detailed bone analyses is in progress. Both hyponatremia and estrogen deficient conditions caused an increase in body weight. In the hyponatremia group, this was probably due to the water retention in the body as well as due to the increase in heart and kidney weight because of the desmopressin treatment and low sodium level. In the Ovx rats, the weight of visceral fat and muscle was increased due the hormone depletion. This study provides new knowledge about hyponatremia induced osteoporosis and shows a negative systemic effect of low sodium level on other organs, thus demonstrating the importance of the treatment of chronic hyponatremia in patients.

Stichwörter Osteoporosis, Hyponatremia, Estrogen, Bone, Rat model

Publication History

Article published online:
15 October 2020