Animal data and cross-sectional human studies have established that chronic hyponatremia predisposes to osteoporosis; the effects of acute hyponatremia on bone remodeling are unknown. Serum markers of bone remodeling (total procollagen type 1 amino-terminal propeptide (P1NP), bone specific alkaline phosphatase (bone ALP), N-mid-osteocalcin (OCI) and C-terminal teleopeptides of type I collagen (CTX-1)) were assessed in a cohort of patients admitted with subarachnoid hemorrhage (SAH), who were prospectively studied over seven days. The ratio of P1NP:CTX-1 was calculated to report a bone formation index.
Twenty-two patients (13 women), median (IQR) age 53 (47, 62) years were recruited. Patients who developed post-SAH ACTH deficiency and those treated with glucocorticoids, or continuous enteral feeding were excluded. All patients were eunatremic on initial assessment. Eight patients developed acute hyponatremia, median nadir plasma sodium concentration (pNa) 131 (128, 132) mmol/L, and 14 remained eunatremic, nadir pNa 136 (133, 137) mmol/L. The groups were matched for age, 25-hydroxy Vitamin D, PTH, WFSS and Fischer scores. Serum cortisol concentration was greater in the hyponatremic group, 571 (504, 671) nmol/L, than the eunatremic group, 449 (400, 501) nmol/L, p=0.008. Bone remodeling markers and bone formation index (P1NP:CTX-1 ratio) were similar in the two groups at baseline.
There was a significant rise in CTX-1 in both hyponatremic patients, +0.15 (0.09, 0.37) μg/l, p = 0.009, and patients who remained eunatremic, +0.11 (-0.02, 0.23) μg/l, p = 0.04, with no significant difference between the groups. There was, however, a significant fall in P1NP:CTX-1 ratio in patients with acute hyponatremia, p = 0.02, but no significant change in eunatraemic patients, with significant between group difference, p = 0.02.
Changes in P1NP and OCI correlated positively with nadir pNa; r = 0.43, p = 0.04 and r = 0.61, p = 0.001 respectively. In addition, there was a positive correlation between change in P1NP:CTX-1 ratio and nadir pNa, r = 0.43, p = 0.04. There was no correlation between change in OCI or CTX-1 and nadir pNa. Serum cortisol was strongly negatively correlated with change in P1NP (r = -0.64, p = 0.001) but not with change in other bone remodeling markers.
Acute hyponatremia following SAH is associated with a fall in bone formation index; physiological hypercortisolemia may contribute to this. Further analysis with larger numbers will help us determine whether hyponatremia is an independent risk factor.