The most common drug used to treat Alzheimer's disease increases bone mass in mice, according to one of the first research articles published in the journal Heliyon. The researchers believe the drug could also be used to treat bone loss diseases like osteoporosis and periodontitis, following further clinical research.
Alzheimer's disease is the most common form of dementia and the incidence is increasing in our aging population. In the early stages of Alzheimer's disease, bone density decreases, putting patients at a higher risk of bone fractures. The new study suggests that treating Alzheimer's disease with a drug called donepezil not only improves cognitive function but also increases bone density, reducing the risk of fractures.
Two different kinds of cell control the bone mass and density in our bodies: osteoblasts make bone and osteoclasts absorb it. A molecule called acetylcholine causes osteoclasts to die in vitro. Although an enzyme called acetylcholinesterase breaks this molecule down, the effect of this enzyme on osteoclasts remains unclear.
The most common drug used to treat Alzheimer's disease, donepezil, stops acetylcholinesterase from working, leading to an increase in the amount of acetylcholine in the brain. Recent retrospective clinical studies have suggested that patients being treated with donepezil for Alzheimer's disease have a lower risk of hip fracture, and that risk was dependent on the dose they were taking.
The researchers wanted to understand how donepezil prevents bone degradation. They looked at the drug's activity in vitro using mouse bone marrow cells, and found that more acetylcholinesterase is produced when osteoclasts are being made, which leads to even more osteoclasts being made. Donepezil stops acetylcholinesterase from working, therefore preventing osteoclasts from being made.
The team also looked at the effect of the drug in a mouse model with bone loss. They found that donepezil increases bone mass in mice by preventing the production of osteoclasts.
"We were surprised to see that donepezil directly inhibits the production of osteoclasts and subsequently increases bone mass in vivo," the researchers said. "This is very surprising point - donepezil directly controls the molecule that is responsible for macrophages becoming osteoclasts."
Previous research has shown that acetylcholinesterase activity increases continuously with age, and may accelerate the risk of bone loss in elderly people. The researchers noted that the concentration of acetylcholinesterase in macrophages was higher when the tissue was inflamed. This suggests that inflammation causes bone to be degraded in part due to acetylcholinesterase production.
The team now plans to startclinical research, and study whether taking donepezil reduces patients' risk of bone fracture compared to a control group.
Based on material originally posted by Elsevier.