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. We examined the effect of increased dietary sodium chloride (NaCl) on bone metabolism and acid-base balance. 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). 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)(-)) and base excess (BE) decreased from phases 1 to 3 (p < 0.001 for both) and from phases 2-3 (HCO(3)(-), p = 0.003; BE, p = 0.015). Nearly all bone resorption markers and acid-base variables reached their baseline levels in phase 4. We conclude that low-grade metabolic acidosis may be the cause of NaCl-induced exaggerated bone resorption.