Low-Grade Metabolic Acidosis May Be the Cause of Sodium Chloride–Induced Exaggerated Bone Resorption

Abstract

Stepwise increase in NaCl intake in healthy male test subjects led to a low-grade metabolic acidosis. This was most likely the cause for increased bone resorption during high sodium chloride intake, as determined by analyzing bone resorption markers. Introduction:We examined the effect of increased dietary sodium chloride (NaCl) on bone metabolism and acid-base balance. Materials and Methods: Subjects were nine healthy men (mean age, 25.7 ± 3.1 yr; mean body weight [BW], 71.5 ± 4.0 kg). During the first period (6 days), subjects received 0.7 mEq NaCl/kg BW per day (phase 1), during the second period (6 days) 2.8 mEq NaCl/kg BW per day (phase 2), during the third period (10 days) 7.7 mEq NaCl/kg BW per day (phase 3), and during the fourth period (6 days) 0.7 mEq NaCl/kg BW per day (phase 4). Results: Twenty-four-hour urinary excretion of calcium and sodium rose significantly with increasing NaCl intake (p < 0.001 for both). Urinary excretion of bone resorption markers C-and N-terminal telopeptide of type I collagen (CTX, NTX) increased from phase 2 to phase 3 (CTX, p = 0.013; NTX, p < 0.001) and decreased from phase 3 to phase 4 (CTX, p < 0.001; NTX, p = 0.002). Bone formation markers N-terminal propeptide of type I procollagen, bone-specific alkaline phosphatase, and osteocalcin remained unchanged from low to high NaCl intake. Blood pH levels decreased (p = 0.04) between phases 1 and 3. Blood bicarbonate (HCO 3

High sodium chloride intake exacerbates immobilization-induced bone resorption and protein losses

“…Increased calcium, NTX, and CTX excretion rates were accompanied by reduced capillary blood bicarbonate (P ϭ 0.018) and base excess (P ϭ 0.009) levels (Table 1), as already shown in ambulatory test subjects (25). During HDBR, bicarbonate concentration with high NaCl intake (25.21 Ϯ 0.33 mmol/l) was lower than during low NaCl intake (26.40 Ϯ 0.47 mmol/l); the same was observed for base excess levels (high NaCl: 0.83 Ϯ 0.31 mmol/l; low NaCl: 2.0 Ϯ 0.43 mmol/l).…”

“…As in ambulatory test subjects (25), increased bone resorption was accompanied by changes in acid-base status characterized as a socalled low-grade metabolic acidosis. According to Vormann and Daniel (69), low-grade metabolic acidosis is characterized by a slight shift of blood pH within the normal range accompanied by a reduction of total buffer capacity.…”

“…Our results support the findings of Frassetto et al: the high NaCl intake during HDBR led to a low-grade metabolic acidosis, which was at least partially caused by ion movement of chloride and HCO 3 Ϫ . But still other possible mechanisms may be involved, as previously mentioned (25). Enforced activity of cellular Na ϩ /H ϩ exchangers (18,36) as well as Na ϩ /H ϩ ion exchanges on the extracellular glycosaminoglycans (19) and/or a Na-induced expansion of extracellular volume, resulting in a decrease in HCO 3 Ϫ reabsorption (3,38,52,58), can contribute to mediation of the effect of NaCl on acid-base balance.…”

“…Standardization and control of the diet, especially the sodium intake, was carried out as described in detail in Frings-Meuthen et al (25).…”

“…Although there is no doubt that increasing NaCl intake causes high calcium excretion (5,34,50), the mechanism that leads to calcium mobilization out of bone remains unknown. In a metabolic balance study, we have recently shown that a very high NaCl intake leads to increased bone resorption in ambulatory test subjects, most likely by inducing a low-grade metabolic acidosis (25). Besides this effect on bone, metabolic acidosis has also been demonstrated to contribute to increases in whole body protein turnover and concomitant decreases in whole body protein content (9,10,54).…”