Bidirectional association between cognitive impairment and bone mineral density reduction in aging populations: A systematic review and meta-analysis of osteoporosis, osteopenia, and bone mineral content

Bone. 2025 Nov:200:117616. doi: 10.1016/j.bone.2025.117616. Epub 2025 Aug 27.

Abstract

Osteoporosis is a skeletal disorder characterized by reduced bone mineral density (BMD), increasing fracture risk. Cognitive disorders (CD), including Alzheimer's disease, dementia, and mild cognitive impairment (MCI), cause cognitive decline and are prevalent among older adults. This systematic review and meta-analysis explores the bidirectional association between cognitive impairment and bone health, specifically low BMD, osteopenia, and osteoporosis. Comprehensive searches were performed in PubMed, Scopus, and the Cochrane Library through August 15, 2024. Eligible observational studies assessing the association between cognitive impairment and BMD were included. Two reviewers independently evaluated studies, with data analyzed using fixed and random-effects models in STATA 17. Risk of bias was assessed with the Newcastle-Ottawa Scale and AHRQ checklist. Fifteen studies involving 93 to 47,579 participants were analyzed. Results showed individuals with cognitive impairment had a significantly higher risk of osteoporosis (log RR: 0.59, 95 % CI: 0.27-0.92, p < 0.001) and a higher risk of osteopenia (log RR: -0.18, 95 % CI: -0.41-0.05). Conversely, those with osteoporosis were more likely to develop cognitive impairment (log RR: 0.34, 95 % CI: 0.19-0.48, p < 0.001). Comparing mean BMD between cognitively impaired individuals and controls revealed lower BMD in the cognitive impairment group: spine (Cohen's d: -0.26, 95 % CI: -0.57-0.04) and femur (Cohen's d: -0.39, 95 % CI: -0.63--0.16). These findings underscore the importance of bone health monitoring in patients with cognitive impairment and preventing cognitive decline in those with osteoporosis. Longitudinal studies with larger, diverse populations are warranted to confirm these results.

Keywords: Alzheimer's disease; Bone mineral density (BMD); Cognitive decline; Cognitive impairment; Dementia; Meta-analysis; Osteoporosis.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Aged
  • Aging* / pathology
  • Bone Density* / physiology
  • Bone Diseases, Metabolic* / complications
  • Bone Diseases, Metabolic* / physiopathology
  • Cognitive Dysfunction* / complications
  • Cognitive Dysfunction* / physiopathology
  • Humans
  • Observational Studies as Topic
  • Osteoporosis* / complications
  • Osteoporosis* / physiopathology