Serum 25 hydroxyvitamin D, bone mineral density and fracture risk across the menopause

J Clin Endocrinol Metab. 2015 May;100(5):2046-54. doi: 10.1210/jc.2014-4367. Epub 2015 Feb 26.


Context: Low levels of serum 25 Hydroxyvitamin D [25(OH)D] have been linked to greater fracture risk in older women.

Objective: This study aimed to determine whether higher 25(OH)D is associated with slower loss of bone mineral density (BMD) and lower fracture risk during the menopausal transition.

Design, setting, and participants: This was a prospective cohort study at five clinical centers in the United States. Mean age was 48.5 ± 2.7 years. The fracture analysis included 124 women with an incident traumatic fracture, 88 with incident nontraumatic fracture, and 1532 women without incident fractures; average followup was 9.5 years. BMD analysis included 922 women with a documented final menstrual period.

Main outcome measures: Serum 25(OH)D was measured by liquid chromatography tandem mass spectrometry at the third annual clinic visit. BMD was measured and incident fractures ascertained at each annual visit.

Results: The mean 25(OH)D was 21.8 ng/mL; seven-hundred two (43%) of the women had 25(OH)D values <20 ng/mL. There was no significant association between 25(OH)D and traumatic fractures. In multivariate adjusted hazards models, the hazard ratio (HR) for nontraumatic fractures (95% confidence interval [CI]) was 0.72 (0.54-0.96) for each 10-ng/mL increase in 25(OH)D. Comparing women whose 25(OH)D was ≥20 vs <20 ng/mL, the HR (95% CI) for fracture was 0.54 (0.32-0.89). Changes in lumbar spine and femoral neck bone mineral density across menopause were not significantly associated with serum 25(OH)D level.

Conclusion: Serum 25(OH)D levels are inversely associated with nontraumatic fracture in mid-life women. Vitamin D supplementation is warranted in midlife women with 25(OH)D levels <20 ng/mL.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Bone Density / physiology*
  • Female
  • Fractures, Bone / blood*
  • Fractures, Bone / epidemiology
  • Fractures, Bone / physiopathology
  • Humans
  • Incidence
  • Menopause / blood*
  • Middle Aged
  • Risk
  • Risk Assessment
  • Vitamin D / analogs & derivatives*
  • Vitamin D / blood


  • Vitamin D
  • 25-hydroxyvitamin D