Increasing cases of Alzheimer’s disease in our aging population is a cause of great concern. It is one of the most common forms of dementia that affects our elderly. In its early stages, Alzheimer's disease is characterized by decreasing bone density, which puts patients at a higher risk of bone fractures.
A new research article published in the new open access journal Heliyon, has revealed that the most common drug used for treating Alzheimer’s disease increases bone mass in mice. This is good news as the authors of the study from Saitama Medical University in Japan point out. The results of the study signify that following further clinical research, the drug could also be used to treat bone loss diseases like osteoporosis and periodontitis.
Donepezil is the commonly used drug to treat Alzheimer's disease. As per the new Heliyon disease, this drug can improve cognitive function as well as increase bone density, thereby reducing the risk of fractures.
Dr. Tsuyoshi Sato, Associate Professor in the Department of Oral and Maxillofacial Surgery, Saitama Medical University and also the lead author of the study said that they are of the opinion that donepezil can improve cognitive function and increase bone mass, making it a very useful drug for patients with dementia and osteoporosis. Since, this drug serves dual purpose, from the viewpoint of medical economics; it will reduce the cost of treating these diseases.
There are two types of cell at work to control bone mass and density in our bodies – osteoblasts make bone and osteoclasts absorb it. A molecule named 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.
It is seen that donepezil, stops acetylcholinesterase from working, leading to an increase in the amount of acetylcholine in the brain. Recent clinical studies seem to suggest that patients who are on donepezil for Alzheimer’s disease have a lower risk of hip fracture. The researchers wanted to further their study and understand how donepezil prevents bone degradation. They observed the drug’s activity in vitro using mouse bone marrow cells, and it was found that more acetylcholinesterase is produced when osteoclasts are being made, which leads to even more osteoclasts being made. Donepezil stops acetylcholinesterase from working, which in turn prevents osteoclasts from being made.
The team then studied the effect this drug has in a mouse model with bone loss. It was found that by preventing the production of osteoclasts, donepezil increases bone mass in mice. Dr. Sato said that it was indeed surprising to find that donepezil directly inhibits the production of osteoclasts and subsequently increases bone mass in vivo. Some of the researches done previously have shown that acetylcholinesterase activity increases continuously with age, and that is the reason why elderly people are at an accelerated risk of bone loss.
The researchers also noted that the concentration of acetylcholinesterase in macrophages was higher when the tissue was inflamed. It suggests that inflammation causes bone to be degraded in part due to acetylcholinesterase production. Dr. Sato seemed very positive about the findings of the study as they are very promising and suggest that there is a role for donepezil in increasing bone mass in elderly patients with inflammation and dementia. Of course, more research is needed to observe the effect of this drug in patients.
To further their studies, the team now plans to work with the Department of Neurology at Saitama Medical University on clinical research. They will study if taking donepezil reduces patients’ risk of bone fracture by looking at its effect in a group of patients compared to a control group.
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