Low-grade metabolic acidosis may be the cause of sodium chloride-induced exaggerated bone resorption

J Bone Miner Res. 2008 Apr;23(4):517-24. doi: 10.1359/jbmr.071118.


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)(-)) 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.

Conclusions: We conclude that low-grade metabolic acidosis may be the cause of NaCl-induced exaggerated bone resorption.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acid-Base Equilibrium
  • Acidosis / physiopathology*
  • Adult
  • Bone Resorption / chemically induced*
  • Bone Resorption / metabolism
  • Calcium / blood
  • Humans
  • Male
  • Parathyroid Hormone / blood
  • Sodium Chloride / toxicity*


  • Parathyroid Hormone
  • Sodium Chloride
  • Calcium