Alzheimer’s Drug Could Prevent Bone Fractures
Research shows donepezil prevents bone loss in mice
Research shows donepezil prevents bone loss in mice
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.
“Donepezil prevents RANKL-induced bone loss via inhibition of osteoclast differentiation by downregulating acetylcholinesterase” by Sato et al. (doi: 10.1016/j.heliyon.2015.e00013). The article appears in Heliyon (September 2015), published by Elsevier.
For a copy of this paper, please contact Mary Beth O’Leary at firstname.lastname@example.org or email@example.com
In online coverage of this paper, please mention the journal Heliyon and link to the paper at http://www.heliyon.com/article/e00013/
Heliyon is an open access journal from Elsevier that publishes robust research across all disciplines. The journal’s team of experts ensures that each paper meeting their rigorous criteria is published quickly and distributed widely. Led by Dr. Claudia Lupp, the editorial team consists of over 600 active researchers who review papers on their merit, validity, and technical and ethical soundness. All published papers are immediately and permanently available on both Heliyon.com and ScienceDirect.
Elsevier is a world-leading provider of information solutions that enhance the performance of science, health, and technology professionals, empowering them to make better decisions, deliver better care, and sometimes make groundbreaking discoveries that advance the boundaries of knowledge and human progress. Elsevier provides web-based, digital solutions — among them ScienceDirect, Scopus, Research Intelligence and ClinicalKey— and publishes over 2,500 journals, including The Lancet and Cell, and more than 35,000 book titles, including a number of iconic reference works. Elsevier is part of RELX Group, a world-leading provider of information and analytics for professional and business customers across industries. www.elsevier.com
Mary Beth O’Leary
Heliyon Marketing & Publicity Manager
+44 (0) 2074 244 343
+44 (0) 7881 330 150