Serum 25-Hydroxyvitamin D Insufficiency in Search of a Bone Disease

J Clin Endocrinol Metab. 2017 Jul 1;102(7):2321-2328. doi: 10.1210/jc.2016-3189.


Context: Vitamin D "insufficiency" and "deficiency" are defined as serum 25-hydroxyvitamin D [25(OH)D] levels <75 and <30 nmol/L, respectively. We aimed to determine whether these values signal hypocalcemia and hypophosphatemia, secondary hyperparathyroidism, high bone remodeling, low areal bone mineral density (aBMD), microstructural deterioration, or reduced matrix mineralization density (MMD) and so suggest whether bone fragility is present.

Methods: Concentrations of 25(OH)D, calcium, phosphate, creatinine, and parathyroid hormone (PTH) were measured in 11,855 participants. Serum C-terminal telopeptide of type 1 collagen, procollagen type 1 N-terminal propeptide (P1NP), aBMD, and distal radius microstructure and MMD were measured in a second subset of 150 participants.

Results: A breakpoint for calcium, PTH, and alkaline phosphatase was identified at a threshold 25(OH)D level <30 nmol/L. There was no plateau beyond 75 nmol/L. In the subgroup with measurements of bone morphology, no associations were detectable between serum 25(OH)D concentration, aBMD, trabecular density, cortical porosity, or MMD. Among 1439 participants with serum 25(OH)D <30 nmol/L, 6.1% had low serum calcium, 3.4% had low serum phosphate, 6.1% had high alkaline phosphatase, and 34.2% had elevated PTH. Most participants did not have any abnormalities.

Conclusion: At a 25(OH)D threshold of ≤30 nmol/L, abnormalities in biochemical features support the notion of a "deficiency" state predisposing to bone disease. However, no deleterious effects were found in participants within an insufficiency threshold of a 25(OH)D level of 30 to 75 nmol/L, which challenges the rationale justifying vitamin D supplementation in these individuals.

MeSH terms

  • Adult
  • Aged
  • Alkaline Phosphatase / blood
  • Bone Density / physiology
  • Bone Diseases / blood
  • Bone Diseases / epidemiology
  • Bone Diseases / etiology*
  • Bone Diseases / physiopathology
  • Bone Remodeling / physiology
  • Calcium / blood
  • Cohort Studies
  • Female
  • Glomerular Filtration Rate
  • Humans
  • Male
  • Middle Aged
  • Parathyroid Hormone / blood
  • Phosphates / blood
  • Victoria / epidemiology
  • Vitamin D / analogs & derivatives*
  • Vitamin D / blood
  • Vitamin D Deficiency / blood
  • Vitamin D Deficiency / complications*
  • Vitamin D Deficiency / epidemiology
  • Vitamin D Deficiency / physiopathology


  • Parathyroid Hormone
  • Phosphates
  • Vitamin D
  • 25-hydroxyvitamin D
  • Alkaline Phosphatase
  • Calcium