Blood biomarkers of osteoporosis in mild cognitive impairment and Alzheimer's disease

J Neural Transm (Vienna). 2009 Jul;116(7):905-11. doi: 10.1007/s00702-009-0241-x. Epub 2009 May 26.


Previous studies revealed some comorbidity of Alzheimer's disease and osteoporosis not only for advanced disease, but also for the incipient conditions cognitive decline and decline of bone mineral density. To detect comorbidity with osteoporosis at a subclinical level, we studied concentrations of biochemical osteoporosis markers in blood plasma of subjects with mild cognitive impairment and mild Alzheimer's disease compared to subjects with primary osteoporosis and age-matched cognitively normal controls in an explorative approach. Regarding disease-spanning molecular pathology we also studied osteoprotegerin, a decoy receptor of RANKL and TRAIL. Equally increased C-terminal collagen fragments, marking bone catabolism, were seen in osteoporosis and Alzheimer's disease (+68%) versus controls. Osteocalcin, marking bone remodelling and anabolism, was concomitantly increased in osteoporosis (+63%), as a trend, and significantly in Alzheimer's disease (+76%). Osteoprotegerin was unchanged between patient groups and controls. 25 (OH) vitamin D plasma levels were low normal and of equal amount in all groups except for the osteoporosis group. These results point to increased bone catabolism and concomitant remodelling/anabolism unrelated to vitamin D state in mild Alzheimer's disease, but not in mild cognitive impairment. This corroborates previous findings of comorbidity of Alzheimer's disease with osteoporosis in the early disease course at the level of biochemical blood markers. Regarding osteoprotegerin, previously reported plasma level increases in Alzheimer's disease were not observed in this study, which does not rule out subtle changes to be detected in larger samples or the possibility that other components of osteoprotegerin pathways are affected in Alzheimer's disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / epidemiology*
  • Biomarkers / analysis
  • Biomarkers / blood
  • Bone Remodeling / physiology
  • Bone and Bones / metabolism*
  • Bone and Bones / physiopathology
  • Cognition Disorders / epidemiology*
  • Collagen / analysis
  • Collagen / blood
  • Comorbidity
  • Female
  • Humans
  • Male
  • Middle Aged
  • Osteocalcin / analysis
  • Osteocalcin / blood
  • Osteoporosis / blood*
  • Osteoporosis / diagnosis
  • Osteoporosis / epidemiology*
  • Osteoprotegerin / analysis
  • Osteoprotegerin / blood
  • Peptide Fragments / analysis
  • Peptide Fragments / blood
  • Predictive Value of Tests
  • Sensitivity and Specificity
  • Vitamin D / analogs & derivatives
  • Vitamin D / analysis
  • Vitamin D / blood
  • Vitamin D Deficiency / blood
  • Vitamin D Deficiency / diagnosis


  • Biomarkers
  • Osteoprotegerin
  • Peptide Fragments
  • Osteocalcin
  • Vitamin D
  • Collagen
  • 25-hydroxyvitamin D