Vitamin D deficiency promotes prostate cancer growth in bone

Prostate. 2011 Jun 15;71(9):1012-21. doi: 10.1002/pros.21316. Epub 2010 Dec 28.


Background: Vitamin D is considered as an important determinant of bone turnover as well as cancer growth. Using a murine model of bone metastasis, we investigated the effect of vitamin D deficiency on prostate cancer cell growth in bone.

Methods: Three-week-old male nude mice were fed either normal chow (control) or a diet deficient in vitamin D. The latter diet resulted in severe hypovitaminosis D within 6 weeks. At this point of time, 5 × 10(4) cells of the prostate cancer cell line, PC-3, were injected either into the bone marrow (tibia) or subcutaneously into soft tissues. Osteoprotegerin (OPG) was co-administered in subgroups of mice to suppress bone remodeling. Osteolytic lesions were monitored by serial X-ray, while soft tissue tumor growth was measured by caliper. All tissues were analyzed by micro-CT and histology at endpoint.

Results: Bone turnover was significantly accelerated in vitamin D deficient compared to vitamin D sufficient mice from week 6 onwards. Intra-tibially implanted PC-3 cells resulted in mixed osteolytic and osteosclerotic lesion. At endpoint, osteolytic and osteosclerotic lesion areas, total tumor area, and tumor mitotic activity were all significantly increased in vitamin D deficient mice compared to controls. Regardless of diet, OPG reduced bone turnover, total tumor, and osteosclerotic area as well as tumor mitotic activity, while promoting cell apoptosis. In contrast, vitamin D deficiency did not alter tumor growth in soft tissues.

Conclusion: Vitamin D deficiency stimulates prostate cancer growth in bone through modulating the bone microenvironment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acid Phosphatase / blood
  • Animals
  • Bone Neoplasms / blood
  • Bone Neoplasms / metabolism
  • Bone Neoplasms / secondary*
  • Bone Remodeling
  • Calcitriol / pharmacology
  • Cell Line, Tumor
  • Histocytochemistry
  • Isoenzymes / blood
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Osteoprotegerin / metabolism
  • Peptide Fragments / blood
  • Procollagen / blood
  • Prostatic Neoplasms / blood
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / pathology*
  • Specific Pathogen-Free Organisms
  • Tartrate-Resistant Acid Phosphatase
  • Tomography, X-Ray Computed
  • Vitamin D / analogs & derivatives
  • Vitamin D / blood
  • Vitamin D Deficiency / blood
  • Vitamin D Deficiency / metabolism
  • Vitamin D Deficiency / pathology*


  • Isoenzymes
  • Osteoprotegerin
  • Peptide Fragments
  • Procollagen
  • procollagen Type I N-terminal peptide
  • Vitamin D
  • 25-hydroxyvitamin D
  • Acid Phosphatase
  • Tartrate-Resistant Acid Phosphatase
  • Calcitriol