Effects of nano calcium carbonate and nano calcium citrate on toxicity in ICR mice and on bone mineral density in an ovariectomized mice model

Nanotechnology. 2009 Sep 16;20(37):375102. doi: 10.1088/0957-4484/20/37/375102. Epub 2009 Aug 26.


Taking calcium supplements can reduce the risk of developing osteoporosis, but they are not readily absorbed in the gastrointestinal tract. Nanotechnology is expected to resolve this problem. In the present study, we examined whether the bioavailability of calcium carbonate and calcium citrate can be improved by reducing the particle size. The morphology of nano calcium carbonate and nano calcium citrate was characterized by dynamic laser-light scattering (DLS), field-emission scanning electron microscopy (FE-SEM) and transmission electron microscopy (TEM). The measurements obtained from DLS, FE-SEM and TEM were comparable. Acute and sub-chronic toxicity tests were performed to establish the safety of these products after oral administration. The no-observed-adverse-effect levels of nano calcium carbonate and nano calcium citrate were 1.3 and 2.3 g kg(-1) body weight, respectively. The results of our in vivo studies indicate that administering nano calcium carbonate and nano calcium citrate can enhance the serum calcium concentration and maintain the whole-body bone mineral density in ovariectomized mice. These data suggest that nano calcium carbonate and nano calcium citrate are more bioavailable than micro calcium carbonate and micro calcium citrate, respectively.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Density / drug effects*
  • Bone Density Conservation Agents / adverse effects
  • Bone Density Conservation Agents / pharmacology*
  • Calcium / blood
  • Calcium Carbonate / administration & dosage
  • Calcium Carbonate / adverse effects
  • Calcium Carbonate / pharmacology*
  • Calcium Citrate / administration & dosage
  • Calcium Citrate / adverse effects
  • Calcium Citrate / pharmacology*
  • Female
  • Male
  • Mice
  • Mice, Inbred ICR
  • Microscopy, Electron, Scanning
  • Microscopy, Electron, Transmission
  • Nanoparticles / administration & dosage
  • Nanoparticles / ultrastructure
  • Ovariectomy*


  • Bone Density Conservation Agents
  • Calcium Carbonate
  • Calcium Citrate
  • Calcium