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Abstract: FR-PO275

The Relation of the 24,25 to 25-Hydroxyvitamin D Ratio with Bone Density and Fracture Risk in Older Adults: The Cardiovascular Health Study

Session Information

Category: Mineral Disease

  • 1202 Mineral Disease: Vitamin D, PTH, FGF-23


  • Ginsberg, Charles, University of California, San Diego, San Diego, California, United States
  • Katz, Ronit, University of Washington, Seattle, Washington, United States
  • de Boer, Ian H., University of Washington, Seattle, Washington, United States
  • Kestenbaum, Bryan R., University of Washington, Seattle, Washington, United States
  • Chonchol, Michel, University of Anschutz Medical Center, Aurora, Colorado, United States
  • Shlipak, Michael, San Francisco VA Medical Center, San Francisco, California, United States
  • Sarnak, Mark J., Tufts Medical Center, Boston, Massachusetts, United States
  • Hoofnagle, Andrew N., University of Washington, Seattle, Washington, United States
  • Rifkin, Dena E., University of California, San Francisco, San Francisco, California, United States
  • Garimella, Pranav S., University of California, San Diego, San Diego, California, United States
  • Ix, Joachim H., University of California, San Diego, San Diego, California, United States

Serum 25-hydroxyvitamin D [25(OH)D] concentrations may not optimally indicate vitamin D receptor (VDR) activity. Catabolism of 25(OH)D to 24,25-dihydroxyvitmin D [24,25(OH)2D] is stimulated by active 1,25-dihydroxyvitamin D. Thus, higher concentrations of 24,25(OH)2D and a higher ratio of 24,25(OH)2D to 25(OH)D (the vitamin D metabolite ratio [VMR]) may provide additional information on receptor activity. We compared the strength of associations of these markers with serum PTH concentrations, hip bone mineral density (BMD), and incident hip fracture among community-living older participants in the Cardiovascular Health Study (CHS).


We conducted a case-cohort study of 1116 CHS participants with over sampling for fracture outcomes. We used multiple linear regression to assess associations of 25(OH)D, 24,25(OH)2D, and VMR with PTH and hip BMD in the random cohort. We used a Cox proportional hazards model to estimate the association of each marker with incident fracture in the complete case-cohort population.


Mean age was 78, 60% were female, and mean eGFR was 64 +/-16 ml/min/1.73m2. Serum 25(OH)D, 24,25(OH)2D, and VMR were each associated with PTH; the sizes of these associations were statistically indistinguishable. Higher serum 24,25(OH)2D concentrations, but not 25(OH)D or VMR, were associated with greater hip BMD. There were 289 hip fractures during 8.4 years mean follow-up. Serum concentrations of 24,25(OH)2D and VMR but not 25(OH)D were associated with incident fracture (Table).


Lower 24,25(OH)2D concentrations and VMR but not 25(OH)D concentrations were associated with hip fracture risk in community-living older adults.

Association of Vitamin D Measures with Incident Hip Fracture
 25-hydroxyvitamin D (ng/ml)24,25-dihydroxyvitamin D (ng/ml)VMR (ng/ml) / (ng/ml)
Hazard Ratio per SD higher (95% CI)0.93 (0.79, 1.10)0.73 (0.61, 0.87)0.74 (0.61, 0.88)

Data for model adjusted for age, sex, race, season of measurements, site of measurement BMI, eGFR, serum calcium, phosphate and FGF-23.


  • NIDDK Support