Increased calcium uptake and improved trabecular bone properties in intestinal alkaline phosphatase knockout mice

J Bone Miner Metab. 2018 Nov;36(6):661-667. doi: 10.1007/s00774-017-0887-7. Epub 2017 Dec 12.


Previous studies have demonstrated a negative correlation between intestinal alkaline phosphatase (IAP) activity and calcium (Ca) absorption in the gut, as IAP acts as a protective mechanism inhibiting high Ca entry into enterocytes, preventing Ca overload. Here we evaluated Ca absorption and bone properties in knockout mice (KO) completely devoid of duodenal IAP (Akp3 -/- mice). Female C57BL/6 control mice (WT, n = 7) and KO mice (n = 10) were used to determine Ca absorption in vivo and by in situ isolated duodenal loops followed by histomorphometric analysis of duodenal villi and crypts. Bone mineral density, morphometry, histomorphometry and trabecular connectivity and biomechanical properties were measured on bones. We observed mild atrophy of the villi with lower absorption surface and a significantly higher Ca uptake in KO mice. While no changes were seen in cortical bone, we found better trabecular connectivity and biomechanical properties in the femurs of KO mice compared to WT mice. Our data indicate that IAP KO mice display higher intestinal Ca uptake, which over time appears to correlate with a positive effect on the biomechanical properties of trabecular bone.

Keywords: Bone properties; Calcium absorption; Intestinal alkaline phosphatase.

MeSH terms

  • Alkaline Phosphatase / deficiency*
  • Alkaline Phosphatase / metabolism
  • Animals
  • Biomechanical Phenomena
  • Bone Density
  • Calcium / blood
  • Calcium / metabolism*
  • Cancellous Bone / metabolism*
  • Duodenum / metabolism
  • Female
  • Femoral Neck Fractures / physiopathology
  • Intestines / enzymology*
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Phosphates / blood


  • Phosphates
  • Alkaline Phosphatase
  • Calcium