Donepezil regulates energy metabolism and favors bone mass accrual.

The autonomous nervous system regulates bone mass through the sympathetic and parasympathetic arms. The sympathetic nervous system (SNS) favors bone loss whereas the parasympathetic nervous system (PNS) promotes bone mass accrual. Donepezil, a central-acting cholinergic agonist, has been shown to down-regulate SNS and up-regulate PNS signaling tones. Accordingly, we hypothesize that the use of donepezil could have beneficial effects in regulating bone mass. To test our hypothesis, two groups of healthy female mice were treated either with donepezil or saline. Differences in body metabolism and bone mass of the treated groups were compared. Body and visceral fat weights as well as serum leptin level were increased in donepezil-treated mice compared to control, suggesting that donepezil effects on SNS influenced metabolic activity. Donepezil-treated mice had better bone quality than controls due to a decrease in osteoclasts number. These results indicate that donepezil is able to affect whole body energy metabolism and favors bone mass in young female WT mice.