Impact of donepezil on bone health in Alzheimer's patients

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

Phase 2 Interventional Duke University · NCT06041789

This study is testing if the medication donepezil can help improve bone health in people with Alzheimer's disease by looking at changes in bone density over a year.

Quick facts

PhasePhase 2
Study typeInterventional
Enrollment45 (estimated)
Ages50 Years and up
SexAll
SponsorDuke University Academic / other
Drugs / interventionsdenosumab, romozosumab, radiation
Locations1 site (Durham, North Carolina)
Trial IDNCT06041789 on ClinicalTrials.gov

What this trial studies

This study investigates the effects of donepezil, an acetylcholinesterase inhibitor, on bone metabolism in individuals diagnosed with Alzheimer's disease-related dementia. Participants will undergo baseline bone density tests and blood sample collections before being randomly assigned to receive either donepezil or a placebo for 12 months. Follow-up assessments will include additional blood samples and repeat bone density tests, along with questionnaires to evaluate their health status throughout the study period. The goal is to understand how donepezil may influence bone mineral density and other factors related to bone health.

Who should consider this trial

Good fit: Ideal candidates are individuals diagnosed with Alzheimer's disease-related dementia who are willing to start treatment with an acetylcholinesterase inhibitor.

Not a fit: Patients currently taking acetylcholinesterase inhibitors or osteoporosis medications are unlikely to benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to improved bone health and reduced fracture risk in patients with Alzheimer's disease.

How similar studies have performed: Previous studies have suggested a potential link between donepezil use and reduced fracture rates, indicating that this approach may hold promise.

Eligibility criteria

Show full inclusion / exclusion criteria
Inclusion Criteria:

1. Diagnosis of cognitive impairment, including clinical assessment, radiographic or laboratory biomarker assessment
2. Willing to initiate treatment for cognitive impairment
3. A) For females: either age \> 55 years, or Age \< 55 years and at least 12 months since last menstrual period B) For males, age \> 50 years
4. Geriatric Depression Scale score \< 6
5. English-speaking

Exclusion Criteria:

1. Currently on acetylcholinesterase inhibitor or memantine
2. History of bradycardia, heart block, long QT, unexplained syncope, or other contraindication for donepezil; subject with ECG showing HR \< 50, PR interval \> 200 ms, QTc \> 440 ms in men or \> 460 ms in women, or evidence of atrioventricular block
3. Currently on osteoporosis medication (e.g., bisphosphonate, SERM, denosumab, teriparatide, abaloparatide, romozosumab, calcitonin)
4. Use of bisphosphonate within last 5 years
5. Use within last 6 months of estrogens or testosterone, androgen deprivation therapy or aromatase inhibitors, antiepileptic, heparin therapy, thiazolidinediones
6. History of disorders associated with secondary osteoporosis: collagen vascular diseases, malabsorption, inflammatory bowel disease, severe liver disease/cirrhosis, hyperthyroidism (endogenous or exogenous)
7. History of fracture of the humerus, wrist, or vertebra due to fall from standing height or less
8. History of hip fracture, hip replacement, or non-ambulatory
9. Long-term use (\>6 months) of corticosteroids
10. History of Parkinson's, HIV, Huntington's disease
11. History of solid organ transplantation
12. History of bariatric surgery or intending to lose weight by bariatric surgery or weight loss medication (e.g. GLP-1 agonist) in the next 12-months
13. Severe kidney impairment (eGFR \< 30 ml/min),
14. Active malignancy currently undergoing chemotherapeutic, surgical, or radiation therapy, except non-melanomatous skin cancer
15. 1-year mortality \> 25%, measured by ePrognosis calculator
16. Planning to move out of the area in the next 12-months
17. Planning surgery in the next 12-months

Where this trial is running

Durham, North Carolina

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
Conditions Osteoporosis
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.