Vitamin D metabolites and calcium absorption in severe vitamin D deficiency

J Bone Miner Res. 2008 Nov;23(11):1859-63. doi: 10.1359/jbmr.080607.


Contrary to frequent claims, vitamin D insufficiency does not generally cause malabsorption of calcium because serum 1,25(OH)(2)D, which is the major determinant of calcium absorption, is maintained by secondary hyperparathyroidism. Nevertheless, because malabsorption of calcium has been described in osteomalacia, there must be a 25(OH)D level below which the serum 1,25(OH)(2)D can no longer be sustained, although it has never been defined. This paper seeks to define it. We examined the records of 3661 patients and found 319 with a serum 25(OH)D < or = 40 nM, in whom calcium absorption, serum calcium, PTH, bone markers, and vitamin D metabolites had been measured. They were grouped according to their serum 25(OH)D into four categories, 0-10, 11-20, 21-30, and 31-40 nM, and differences between the groups were tested by ANOVA. Correlations between the variables were also examined. Serum calcium, 1,25(OH)(2)D, and calcium absorption were significantly decreased and serum PTH and alkaline phosphatase (ALP) and urine hydroxyproline were increased in those with 25(OH)D < or = 10 nM. Serum ALP and urine hydroxyproline were more strongly related, inversely, to calcium absorption than to the vitamin D metabolites. We conclude that vitamin D deficiency does not reduce serum 1,25(OH)(2)D, and therefore calcium absorption, until the serum 25(OH)D falls to approximately 10 nM. At this level, the substrate concentration seems to be insufficient to maintain the level of the dihydroxy metabolite despite secondary hyperparathyroidism. Further studies are needed to see how these changes correlate with the histological changes of osteomalacia.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Alkaline Phosphatase / blood
  • Calcitriol / blood
  • Calcium / metabolism*
  • Creatinine / urine
  • Fasting / urine
  • Female
  • Humans
  • Hydroxyproline / urine
  • Intestinal Absorption / physiology
  • Male
  • Middle Aged
  • Parathyroid Hormone / blood
  • Regression Analysis
  • Vitamin D / blood
  • Vitamin D / metabolism*
  • Vitamin D Deficiency / blood
  • Vitamin D Deficiency / metabolism*


  • Parathyroid Hormone
  • Vitamin D
  • Creatinine
  • Alkaline Phosphatase
  • Calcitriol
  • Hydroxyproline
  • Calcium