Acetylcholinesterase inhibitors and the risk of hip fracture in Alzheimer's disease patients: A case-control study

Abstract

Recent studies have reported the presence of acetylcholine (ACh) receptor subtypes in bone tissue, and have demonstrated that inhibition of the ACh receptors has negative effects on bone mass and fracture healing capacity. However, little is known about the potential clinical effects that increased ACh signaling might have on bone. Accordingly, this study was designed to determine whether the use of acetylcholinesterase inhibitors (AChEIs), a group of drugs that stimulate ACh receptors and are used to treat Alzheimer's disease (AD), is associated with a decreased risk of hip fracture in AD patients. To accomplish this objective, a case-control analysis was performed using the AD population, aged above 75 years, based in the local health area of the Carlos Haya Hospital, in Malaga, Spain. The cases were 80 AD patients that suffered a hip fracture between January 2004 and December 2008. The controls were 2178 AD patients without hip fracture followed at our health care area during the same period of time. Compared with patients who did not use AChEIs, the hip fracture adjusted odds ratio (OR) for users of AChEIs was 0.42 (95% confidence interval [CI], 0.24-0.72), for users of rivastigmine was 0.22 (95% CI, 0.10-0.45), and for users of donepezil was 0.39 (95% CI, 0.19-0.76). Data were adjusted for the following parameters: body mass index, fall risk, smoking habits, cognition, dependence, degree of AD, comorbidity score, treatment with selective serotonin reuptake inhibitors, age, and gender. Our data suggests that use of AChEIs donepezil and rivastigmine is associated with a reduced risk of fractures in AD patients. Many elderly patients with AD disease who are at risk of developing osteoporosis may potentially benefit from therapy with the AChEIs donepezil and rivastigmine. ß

Acetylcholinesterase Inhibitors Are Associated with Reduced Fracture Risk among Older Veterans with Dementia

“…Evidence suggesting a benefit of AChEI use on bone health has slowly emerged . Bone homeostasis is regulated by local autocrine and paracrine mechanisms and neuronal signals from the autonomic nervous system; similarly, the autonomic nervous system is also implicated in dementia .…”

“…Evidence from in vivo studies shows that administration of a peripherally acting AChEI, pyridostigmine, raises acetylcholine levels and increased trabecular bone mass in mice by inhibiting osteoclasts and bone resorption . Available clinical studies, though few, support improved bone health with use of AChEIs . In older adults with AD, use of centrally acting AChEIs such as donepezil and rivastigmine is associated with reduced hip fracture risks .…”

“…in vivo studies show increase in overall bone mass and whole‐body energy among donepezil‐treated mice, possibly by inhibiting receptor activator of NF‐κB ligand (RANKL)‐induced osteoclast differentiation . Studies in human subjects have been very few but suggest that AChEIs may confer protection against fractures, accelerate bone healing, and reduce both fracture complications and all‐cause mortality post‐hip fracture . Concerns about small sample sizes and risk of bias have limited the application and generalizability of these initial studies.…”

Antihypertensive Medications and the Survival Rate of Osseointegrated Dental Implants: A Cohort Study

“…Preoperatively, patient information including medications, habits, and behavioral factors was self‐reported using a standardized questionnaire that was filled prior to the surgical intervention. Patients with a severe systemic disease [American Society of Anesthesiology III or IV], pregnant, or with a medical disorder known to substantially affect bone metabolism, such as osteoporosis, osteomalacia, Paget's disease, vitamin D deficiency, hyperthyroidism, uncontrolled diabetes, cancer [excluding nonmelanoma skin cancer], or alcoholism, as well as those on corticosteroids, antiepileptic drugs, selective serotonin reuptake inhibitors, proton pump inhibitors, bisphosphonates . Patients with implants with diameters narrower than 4 mm were excluded because adjustment for this confounder was not possible due to the very few number of implants narrower than 4 mm in our cohort ( n = 60), and none of them was placed in antihypertensive drugs users.…”

Early Evidence of Low Bone Density and Decreased Serotonergic Synthesis in the Dorsal Raphe of a Tauopathy Model of Alzheimer’s Disease

“…Contrary to assumptions that skeletal problems result from the advanced disease state of AD, bone loss is reported very early in the progression of AD when cognitive decline is minimal and mobility has not yet been compromised [10–12]. In fact, comorbid bone deficits in AD have been shown to be independent of age, body mass index, physical activity [13, 14], and cognitive state [15]. Thus, it has been hypothesized that bone integrity may represent a component of a prodromal state of AD occurring years before evidence of dementia [14, 16].…”