gms | German Medical Science

Objectives: Bone fractures in the osteoporotic patient represent a challenge to the surgeon. Osteoporosis complicates both fracture treatment and healing. Animals and clinical studies showed that chronic hyponatremia can cause osteoporosis. We have observed that hyponatremia induced osteoporosis developed faster than osteoporosis induced by estrogen deficiency. The present study evaluates the impact of both hyponatremia and estrogen deficiency on bone healing in a female rat model.

Methods: Seven-month old female Sprague Dawley rats were divided into 6 groups (n=8/group): (1) sham-ovariectomized normonatremic rats (Sham-Ovx+NormoNa), (2) Sham+Ovx hyponatremic rats (Sham-Ovx+HypoNa), (3) Sham-Ovx+HypoNa-corrected (cor), (4) ovariectomized rats (Ovx+NormoNa), (5) Ovx+HypoNa, (6) Ovx+HypoNa-cor. Rats were infused with desmopressin at a rate 5 ng/h via a subcutaneous implanted osmotic pumps (Alzet, Durect Co., USA) to induce hyponatremia. NormoNa groups received saline solution in pumps. Sham-Ovx or Ovx was performed at week 0. A bilateral transverse osteotomy of the tibia metaphysis with plate osteosynthesis was performed at week 6 after Ovx in all rats. The pumps were implanted at week 0 and either replaced in HypoNa groups or removed in HypoNa-cor groups at week 6 after Ovx. All animals received liquid rodent diet (BioServ, USA) and demineralized water without restrictions throughout the experiment. Twelve weeks after Ovx, serum was collected, inner organs were weighed and bone healing was examined by micro-CT analysis. Statistical analysis was performed using one-way ANOVA and Tukey-test (p <0.05).

Results and Conclusion: In serum, hyponatremia was confirmed in Sham-Ovx+HypoNa and Ovx+HypoNa rats (110+5 and 108+8 mmol/L), whereas in NormoNa and NormoNa-cor groups, sodium concentration averaged to 140+2 mmol/L. A similar pattern was observed in calcium and magnesium concentrations. Weight of kidney and heart was higher in both HypoNa groups, after sodium correction it returned to the NormoNa levels. Micro-CT analysis at the osteotomy site revealed decreased bone mineral density and bone volume fraction in both HypoNa groups compared with two respective NormoNa groups. The removal of pumps enhanced bone parameters to the level observed in NormoNa groups. The combined effect of Ovx and HypoNa was worse than only Ovx or HypoNa alone. Further biomechanical and histomorphological analyses of bone healing are in progress.

Concluding, both hyponatremia and estrogen deficient conditions impaired bone healing and the combination of these two factors had synergetic detrimental effect. The correction of hyponatremia recovered bone and other parameters to the level observed in NormoNa rats. This study provides new knowledge about the negative impact of hyponatremia on bone healing, especially if it is combined with estrogen deficiency and shows a systemic effect on other organs and serum electrolytes, thus demonstrating the importance of the treatment of chronic hyponatremia in patients with fractures.