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Alzheimer's drug could prevent bone fractures

Research shows donepezil prevents bone loss in mice

Date:
September 21, 2015
Source:
Elsevier
Summary:
The most common drug used to treat Alzheimer's disease increases bone mass in mice, according to a recent article. Researchers say this means the drug could also be used to treat bone loss diseases like osteoporosis and periodontitis, following further clinical research.
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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 new open access journal Heliyon. The authors of the study, from Saitama Medical University in Japan, say this means 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 Heliyon 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.

"We think that donepezil can improve cognitive function and increase bone mass, making it a very useful drug for patients with dementia and osteoporosis," said lead author Dr. Tsuyoshi Sato, Associate Professor in the Department of Oral and Maxillofacial Surgery, Saitama Medical University. "From the viewpoint of medical economics, this dual purpose could reduce the cost of treating these diseases."

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," said Dr. Sato. "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.

"Our findings are very promising and suggest that there is a role for donepezil in increasing bone mass in elderly patients with inflammation and dementia," said Dr. Sato. "There is still work to be done and we look forward to observing the effect of this drug in patients."

The team now plans to work with the Department of Neurology at Saitama Medical University on clinical research. They plan to study whether taking donepezil reduces patients' risk of bone fracture by looking at its effect in a group of patients compared to a control group.


Story Source:

Materials provided by Elsevier. Original written by Mary Beth O'Leary. Note: Content may be edited for style and length.


Journal Reference:

  1. Tsuyoshi Sato, Yuichiro Enoki, Yasushi Sakamoto, Kazuhiro Yokota, Masahiko Okubo, Masahito Matsumoto, Naoki Hayashi, Michihiko Usui, Shoichiro Kokabu, Toshihide Mimura, Yoshihiko Nakazato, Nobuo Araki, Toru Fukuda, Yasushi Okazaki, Tatsuo Suda, Shu Takeda, Tetsuya Yoda. Donepezil inhibits osteoclast differentiation in vitro and prevents RANKL-induced bone loss in vivo. Heliyon, 2015; 1 (1): e00013 DOI: 10.1016/j.heliyon.2015.e00013

Cite This Page:

Elsevier. "Alzheimer's drug could prevent bone fractures." ScienceDaily. ScienceDaily, 21 September 2015. <www.sciencedaily.com/releases/2015/09/150921090149.htm>.
Elsevier. (2015, September 21). Alzheimer's drug could prevent bone fractures. ScienceDaily. Retrieved March 28, 2024 from www.sciencedaily.com/releases/2015/09/150921090149.htm
Elsevier. "Alzheimer's drug could prevent bone fractures." ScienceDaily. www.sciencedaily.com/releases/2015/09/150921090149.htm (accessed March 28, 2024).

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