Alzheimer's disease and osteoporosis

Abstract

Alzheimer's disease (AD) and osteoporosis are both common degenerative diseases in the elderly population. The incidence of both diseases increases with age and will be posing enormous societal burden worldwide. It may appear that AD and osteoporosis are two distinct diseases although many risk factors are shared. Previous observational studies have shown that patients with osteoporosis have higher risks of developing AD than those who do not have osteoporosis. Although osteoporosis, falls, and fractures are more often seen in patients with AD than other older adults, the association between these two diseases may be due to a pathophysiological link rather than one condition causing the other. Several in vitro and in vivo studies lend support to this notion. Patients with AD have excessive amyloid plaques in the brain, and the pathology may extend to peripheral organs and cause skeletal amyloid deposition, which would enhance receptor activator nuclear factor-kappa B ligand signaling and lead to greater osteoclast activities. Patients with osteoporosis may have Vitamin D deficiency or lower levels of Vitamin D binding protein, which protects against amyloid aggregation, thus linking Vitamin D deficiency and AD or osteoporosis and AD. Osteoporosis coexisting with AD provides a window to examine the amyloid hypothesis from peripheral tissues. Future studies are warranted to clarify the role of genetic background regarding Vitamin D levels, exposure to sunlight, estrogen replacement therapy, and physical activity in patients with both chronic diseases.

Keywords: Alzheimer's disease; Amyloid; Osteoporosis; Vitamin D.

Figure 1

The proposed mechanism of amyloid deposition and Vitamin D in the pathogenesis of Alzheimer's disease and osteoporosis. NF-κB: Nuclear factor kappa B, Aβ: Amyloid beta peptide, RANK: Receptor activator NF-κB, RANKL: Receptor activator NF-κB ligand; IκB: Inhibitor of NF-κB, TRAF-6: Tumor necrosis factor receptor-associated factor-6, MEK1: Mitogen-activated protein kinase kinase-1, ERK: Extracellular signal-regulated kinase, OSCAR: Osteoclast-associated receptor, NFATc1: Nuclear factor of activated T-cells-cytoplasmic 1, HP-tau: Hyperphosphorylated tau, DBP: Vitamin D binding protein