Mechanistic complexities of bone loss in Alzheimer's disease: a review.


Mechanistic complexities of bone loss in Alzheimer's disease: a review.


Frame Gabrielle; Bretland Katie A; Dengler-Crish Christine M


Connective Tissue Research




Purpose/Aim: Alzheimer's disease (AD), the primary cause of dementia in the elderly, is one of the leading age-related neurodegenerative diseases worldwide. While AD is notorious for destroying memory and cognition, dementia patients also experience greater incidence of bone loss and skeletal fracture than age-matched neurotypical individuals, greatly impacting their quality of life. Despite the significance of this comorbidity, there is no solid understanding of the mechanisms driving early bone loss in AD. Here, we review studies that have evaluated many of the obvious risk factors shared by dementia and osteoporosis, and illuminate emerging work investigating covert pathophysiological mechanisms shared between the disorders that may have potential as new risk biomarkers or therapeutic targets in AD. Conclusions: Skeletal deficits emerge very early in clinical Alzheimer's progression, and cannot be explained by coincident factors such as aging, female sex, mobility status, falls, or genetics. While research in this area is still in its infancy, studies implicate several potential mechanisms in disrupting skeletal homeostasis that include direct effects of amyloid-beta pathology on bone cells, neurofibrillary tau-induced damage to neural centers regulating skeletal remodeling, and/or systemic Wnt/Beta-catenin signaling deficits. Data from an increasing number of studies substantiate a role for the newly discovered "exercise hormone" irisin and its protein precursor FNDC5 in bone loss and AD-associated neurodegeneration. We conclude that the current status of research on bone loss in AD is insufficient and merits critical attention because this work could uncover novel diagnostic and therapeutic opportunities desperately needed to address AD.;


Aging; Alzheimer’s; bone density; dementia; osteoporosis

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Frame Gabrielle; Bretland Katie A; Dengler-Crish Christine M, “Mechanistic complexities of bone loss in Alzheimer's disease: a review.,” NEOMED Bibliography Database, accessed July 18, 2024,