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Donepezil: Positive Side Effects Of This Alzheimer's Drug Could Benefit Patients With Osteoporosis

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Donepezil (Aricept), prescribed for Alzheimer's disease, increased bone mass in mice. Someday this drug may be used for osteoporosis. epSos.de, CC by 2.0

Sometimes a common side effect of a drug may be beneficial to those who take it. Aricept (donepezil), which is prescribed for Alzheimer's disease, increases bone mass in mice, a new study finds. Researchers from Saitama Medical University in Japan say further studies are needed to see if the drug might be used to treat bone loss diseases such as osteoporosis, a common ailment of the elderly.

As many as half of all women and a quarter of men over the age of 50 will break a bone due to osteoporosis. This disease, which currently affects more than 40 million Americans, weakens and thins the bones, making them fragile. Once adults reach their mid-60s, many will be dealing with the earliest symptoms of Alzheimer’s disease, a common form of dementia that affects about five million Americans. This progressive memory loss disease is often treated with a prescription drug known as donepezil (which includes the brand name Aricept).

The way donepezil helps Alzheimer's patients is it stops acetylcholinesterase from destroying a molecule that performs as a neurotransmitter in the brain. This molecule (acetylcholine) helps brain cells talk to each other (transmit synapses) when trying to perform their jobs together. Naturally, a low level of acetylcholine would mean the neurons as well as the brain itself would not be able to function well.

While Donepezil crosses the blood-brain barrier to work on neurons, some of the drug remains within the body at large. Recent research has found that patients taking donepezil had a lower risk of hip fracture, suggesting the drug may have a direct effect on bone cells. The new study investigated this idea.

Double Duty Drug

Lead author Dr. Tsuyoshi Sato, an associate professor at Saitama Medical University, and his colleagues began their research from the perspective of bone tissue. It is well-known that two different kinds of cell control bone mass and bone density: Osteoblasts make bone and osteoclasts absorb it. This balanced alternation between osteoclasts and osteoblasts is how our bones continuously renew themselves.

Past research has shown that acetylcholine kills osteoclasts in vitro (outside the body), and it is known acetylcholinesterase breaks down acetylcholine. Putting these two ideas together, the researchers asked, what would donepezil (an acetylcholinesterase) do to osteoclasts?

Experimenting on the bone marrow cells of mice, the researchers discovered that donepezil directly inhibited the production of osteoclasts, which subsequently increased bone mass.

"Our findings are very promising and suggest that there is a role for donepezil in increasing bone mass in elderly patients," Sato stated in a press release. He and his team are continuing to study the drug in the belief that someday donepezil may perform double duty, curing two old age ailments at once.

Source: Sato T, Enoki Y, Sakamoto Y, et al. Donepezil prevents RANKL-induced bone loss via inhibition of osteoclast differentiation by downregulating acetylcholinesterase. Heliyon. 2015.

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