Bone Abstracts

Background: Alzheimer’s dementia (AD) and osteoporosis (OP) are common and parallel ageing and frequently coexist in an ageing population. Low BMD appears related to increased risk of AD. Various clinical conditions have been shown to alter acetylcholine (Ach) signalling and affect bone. Ach receptor (AchR) subunits and Ach esterase (AchE) are expressed in bone. Presynaptic Botox inhibit Ach release and impair bone healing and decrease bone mineral content. Poliomyelitis destroys motor neurons that use Ach. Patients have impaired bone growth and a larger proportion develop OP. Smoking; high nicotine; interact and desensitize nAchR affecting bone remodelling negatively. Anti-dementia drugs inhibit AchE. Donepezil and Rivastigmine bind nAChER and mAChER. Galantamine binds mAChER only. We hypothesised that acetylcholine esterase inhibitors (AchEI) as used in dementia management would reduce osteoclastogenesis if this was the mechanism of bone effect of Ach.

Methods: BMMs are seeded at 6×10³ cells/well in 96-well plate. Before RANKL stimulation, cultures were incubated with the drugs Donepezil and Galantamine at equimolar concentrations of 0.1–5.0 μM. Control plates were incubated with and without RANKL only for comparison.

Results: At equimolar concentrations Donepezil inhibit, whereas Galantamine enhances osteoclastogenesis. Donepezil inhibited osteoclastogenesis at the lowest concentration of 0.1 μM.

Conclusion: This data suggests Ach may be important in bone biology. AchEI that bind to nAchR may have the additional benefit of reducing osteoclastogenesis. Donepezil and Galantamine both bind nAChER. This finding is consistent with a recently published case control study confirming the protective effect of Donepezil and Rivastigmine but not Galantamine in hip fracture reduction. This may have important implications for osteoporosis management in older and dementia populations.