Effect of Acetylcholinesterase Inhibitors on Bone Metabolism

Study Overview
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Brief Summary
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People with Alzheimer's disease are at an increased risk of bone fracture. Some studies have shown that those taking donepezil have a lower rate of bone fractures, but the reasons for this are unknown. The purpose of this study is to measure the effect of donepezil treatment on bone metabolism factors including bone mineral density, bone turnover markers, and bone quality. Participants in this study will have a bone density test and have blood samples collected at the baseline study visit. Participants will then be randomly assigned to donepezil or matching placebo to be taken daily by mouth for 12 months. Blood samples will be collected at 6 and 12 months. A repeat bone density test will be performed at 12 months. Participants will also complete questionnaires at each study visit.

Official Title
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Effect of Acetylcholinesterase Inhibitors on Bone Metabolism and Fracture Risk Factors Among Older Adults With Mild to Moderate Alzheimer's Disease

Conditions
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Osteoporosis

Intervention / Treatment
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* Drug: Donepezil
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of ADRD, including clinical assessment and either radiographic or laboratory biomarker assessment Meets NIA-AA clinical dementia criteria Willing to initiate treatment with AchEI for ADRD MoCA score < 24 For females, either age > 55 years, or Age < 55 years and at least 12 months since last menstrual period For males, age > 50 years Geriatric Depression Scale score < 6 Exclusion Criteria: Currently on acetylcholinesterase inhibitor Currently on osteoporosis medication (e.g., bisphosphonate, SERM, denosumab, teripar-atide, abaloparatide, romozosumab) Use of bisphosphonate within last 2 years Use within last 6 months of estrogens or testosterone, androgen deprivation therapy or aromatase inhibitors, antiepileptic, heparin therapy, thiazolidinediones History of disorders associated with osteoporosis: collagen vascular diseases, malab-sorption, inflammatory bowel disease, severe liver disease/cirrhosis, hyperthyroidism (endogenous or exogenous) History of hip fracture, hip replacement, or non-ambulatory Long-term use (>6 months) of corticosteroids History of Parkinson's, HIV, Huntington's disease History of solid organ transplantation Severe kidney impairment (eGFR < 30 ml/sec), Active malignancy, except non-melanomatous skin cancer 1-year mortality > 25%, measured by ePrognosis calculator Initiation of investigational or FDA-approved anti-amyloid drug

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Donepezil<br> | Drug: Donepezil<br>* 10 mg tablet<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Donepezil placebo tablet<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in bone mineral density, as measured by dual x-ray absorptiometry (DXA) |  | baseline, 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in bone resorption marker C-terminal telopeptide (CTX) | measured using commercially available ELISA test on serum | baseline, 6 months, 12 months | 
| Change in bone formation marker amino-terminal propeptide of type I procollagen (P1NP) | measured using commercially available ELISA test on serum | baseline, 6 months, 12 months | 
| Change in Trabecular Bone score | measure of bone quality, using DXA spine images | baseline, 12 months |