Oral Presentation ANZBMS-MEPSA-ANZORS 2022

Treating osteoporosis and dementia with anti-dementia medication acetylcholinesterase inhibitors may have therapeutic benefits on osteoporotic bone by attenuating osteoclastogenesis and bone resorption (#4)

Charles Inderjeeth 1 , Shangfu Li 2 , Dian Teguh 3 , Depeng Wu 2 , Lesong Liu 2 , Jinbo Yuan 3 , Jiake Xu 3
  1. North Metropolitan Health & University of Western Australia, Nedlands, WA, Australia
  2. Spine Surgery, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
  3. School of Biomedical Science, University of Western Australia, Perth, Western Australia, Australia

Background; Osteoporosis and dementia are common and often concurrent in ageing populations. Identifying common pathogenesis and treatment targets may be useful.

Aims: This study was designed to determine whether the use of acetylcholinesterase inhibitors (AChEIs), a group of drugs that stimulate Acetylcholine receptors and used to treat Alzheimer’s disease, is associated with osteoporosis protection and inhibition of osteoclast differentiation and function.

Methods: We examined the effects of AChEI on RANKL-induced osteoclast differentiation and function with osteoclastogensis and bone resorption assays. Next, we investigated impacts of AChEIs on RANKL-induced NF-κB and NFATc1 activation and expression of osteocalst marker genes of CA-2, CTSK and NFATc1, and dissected the MAPK signaling in osteoclasts in vitro by using luciferase assay and Western Blotting. Finally, we assessed the in vivo efficacy of AChEIs using an ovariectomy -induced osteoporosis model, which was analyzed using micro-computed tomography, in vivo osteoclast and osteoblast parameters were assessed using bone histomorphometry.

Results: We found that Donepezil and Rivastigmine inhibited RANKL-induced osteoclastogenesis and impaired osteoclastic activity and bone resorption. Moreover, AChEIs reduced the RANKL-induced transcription of NFATc1, and expression of osteocalst marker genes to varying degrees (mainly Donepezil and Rivastigmine but not Galanthamine). Furthermore, AChEIs variably inhibited RANKL-indued MAPK signaling. Finally, AChEIs protected against OVX-induced bone loss mainly by inhibiting osteoclast activity.

Conclusions: AChEIs (mainly Donepezil and Rivsatigmine) exerted powerfull effect on bone protection by inhibiting osteoclast function through MAPK signaling pathway. Our findings will influence drug choice in those patients with both Alzheimer’s disease and osteoporosis.

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