Association of Bone Mineral Density and Dementia: The Rotterdam Study

Abstract

Background and objectives: Low bone mineral density (BMD) and dementia commonly co-occur in older individuals, with bone loss accelerating in patients with dementia due to physical inactivity and poor nutrition. However, uncertainty persists over the extent to which bone loss already exists before onset of dementia. Therefore, we investigated how dementia risk was affected by BMD at various skeletal regions in community-dwelling older adults.

Methods: In a prospective population-based cohort study, BMD at the femoral neck, lumbar spine, and total body and the trabecular bone score (TBS) were obtained using dual-energy X-ray absorptiometry in 3,651 participants free from dementia between 2002 and 2005. Persons at risk of dementia were followed up until January 1, 2020. For analyses of the association between BMD at baseline and the risk of incident dementia, we used Cox proportional hazards regression analyses, adjusting for age, sex, educational attainment, physical activity, smoking status, body mass index, systolic and diastolic blood pressure, cholesterol level, high-density lipoprotein cholesterol, history of comorbidities (stroke and diabetes mellitus), and APOE genotype.

Results: Among the 3,651 participants (median age 72.3 ± 10.0 years, 57.9% women), 688 (18.8%) developed incident dementia during a median of 11.1 years, of whom 528 (76.7%) developed Alzheimer disease (AD). During the whole follow-up period, participants with lower BMD at the femoral neck (per SD decrease) were more likely to develop all-cause dementia (hazard ratio [HR] _{total follow-up} 1.12, 95% CI 1.02-1.23) and AD (HR_{total follow-up} 1.14, 95% CI 1.02-1.28). Within the first 10 years after baseline, the risk of dementia was greatest for groups with the lowest tertile of BMD (femoral neck BMD, HR_{0-10 years} 2.03; 95% CI 1.39-2.96; total body BMD, HR_{0-10 years} 1.42; 95% CI 1.01-2.02; and TBS, HR_{0-10 years} 1.59; 95% CI 1.11-2.28).

Discussion: In conclusion, participants with low femoral neck and total body BMD and low TBS were more likely to develop dementia. Further studies should focus on the predictive ability of BMD for dementia.

Figure 1. Flowchart for Participants With Bone Mineral Density Scans Included in the Study

Figure 2. Kaplan-Meier Curves of Dementia-Free Survival at Different Levels of Bone Mineral Density at Each Site

Figure 3. Associations of Low BMD of the Total Body (A), the Femoral Neck (B), the Lumbar Spine (C), and Trabecular Bone (D) Scores With the Risk of All-Cause Dementia, Stratified by Sex and APOE-ε4 Allele Carriership

Participants in the highest tertile of BMD were regarded as the reference group (hidden). Estimated HRs were obtained after adjustment of (if applicable) age, sex, APOE genotype, education attainment, physical activity, smoking status, body mass index, systolic and diastolic blood pressure, total cholesterol levels, high-density lipoprotein cholesterol levels, and history of comorbidities (stroke and diabetes mellitus). *The tertile categories of BMD and trabecular bone score were derived by generating tertiles from the residuals of linear regression models adjusted for age (continuously) and sex. The highest tertile was considered as the reference group. BMD = bone mineral density; HR = hazard ratio.