Effect of Acetylcholinesterase Inhibitors on Bone Metabolism

Inclusion criteria

• Diagnosis of cognitive impairment, including clinical assessment, radiographic or laboratory biomarker assessment
• Willing to initiate treatment for cognitive impairment
• 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
• Geriatric Depression Scale score < 6
• English-speaking

Exclusion criteria

• Currently on acetylcholinesterase inhibitor or memantine
• 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
• Currently on osteoporosis medication (e.g., bisphosphonate, SERM, denosumab, teriparatide, abaloparatide, romozosumab, calcitonin)
• Use of bisphosphonate within last 5 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 secondary osteoporosis: collagen vascular diseases, malabsorption, inflammatory bowel disease, severe liver disease/cirrhosis, hyperthyroidism (endogenous or exogenous)
• History of fracture of the humerus, wrist, or vertebra due to fall from standing height or less
• 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
• 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
• Severe kidney impairment (eGFR < 30 ml/min),
• Active malignancy currently undergoing chemotherapeutic, surgical, or radiation therapy, except non-melanomatous skin cancer
• 1-year mortality > 25%, measured by ePrognosis calculator
• Planning to move out of the area in the next 12-months
• Planning surgery in the next 12-months