Hyponatremia does not cause further bone loss in estrogen-deficient rats

Introduction: Previously, we have shown that hyponatremia (HypoNa) impairs bone tissue to a similar extent as estrogen deficiency and that both factors have a synergistic adverse effect on bone healing.The present study investigated whether HypoNa worsens the effect of estrogen depletion on bone in an ovariectomized rat model for postmenopausal osteoporosis.

Methods: Seven-month-old female Sprague-Dawley rats were divided into 4 groups (n=8/group): (1) sham-ovariectomized normonatremic (Sham-NormoNa), (2) ovariectomized (Ovx) NormoNa, (3) Ovx hyponatremic (HypoNa) (4) Ovx HypoNa-corrected (HypoNa-cor). HypoNa was induced by desmopressin via subcutaneous osmotic pumps. NormoNa groups received 0.9% saline solution. Immediately after Ovx, pumps were implanted and either replaced in the HypoNa group or removed in the HypoNa-cor group at week 6. All animals received liquid rodent diet and demineralized water without restrictions. At week 12, the fourth lumbar vertebral body (L4) and both femora underwent biomechanical and micro-computed tomographical analyses. Statistical analysis was performed by ANOVA and Tukey-test (p < 0.05).

Results: The serum sodium level was the lowest in the Ovx-HypoNa group (108±7 mmol/L), in the other 3 groups it averaged 139±7 mmol/L. Calcium and magnesium levels were diminished by HypoNa and also lowered by Ovx. Bone structure in L4 and femur and biomechanical parameters in femur were impaired in all Ovx groups, whereas HypoNa had no additional effect. Desmopressin discontinuation normalized serum Na, but did not improve bone.

Discussion: The detrimental effect of estrogen deficiency on bone was so strong that it overwhelmed the negative effect of HypoNa previously observed in healthy and healing bone. HypoNa was induced immediately after Ovx, when rapid bone loss and metabolic changes occur, and appeared to be less relevant at this time. Further studies could evaluate the impact of HypoNa in an already osteoporotic rat model, which would more closely mimic the situation in osteoporotic patients.

Keywords: Hyponatremia, Bone, Estrogen deficiency, Rat model

Korrespondenzadresse: Marina Komrakova, Universitätsmedizin Göttingen, Unfallchirurgie, Orthopädie und Plastische Chirurgie, Robert-Koch-Str. 40, 37075 Göttingen, Deutschland, E-Mail: [e-mail]