Systematic Reviews
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Orthop. May 18, 2017; 8(5): 412-423
Published online May 18, 2017. doi: 10.5312/wjo.v8.i5.412
Dementia and osteoporosis in a geriatric population: Is there a common link?
Candice L Downey, Adam Young, Emily F Burton, Simon M Graham, Robert J Macfarlane, Eva-Maria Tsapakis, Eleftherios Tsiridis
Candice L Downey, Emily F Burton, University of Leeds, School of Medicine, Leeds LS2 9NL, United Kingdom
Adam Young, Department of Anaesthetics, Pinderfields Hospital, Wakefield WF1 4DG, United Kingdom
Simon M Graham, Robert J Macfarlane, Department of Trauma and Orthopaedics, the Royal Liverpool University Hospital, Liverpool L7 8XP, United Kingdom
Eva-Maria Tsapakis, Eleftherios Tsiridis, Academic Department of Orthopaedics and Trauma, Aristotle University Medical School, 54124 Thessalonika, Greece
Author contributions: Downey CL and Young A contributed equally to this work; Downey CL and Tsiridis EM designed the research; Downey CL, Young A and Burton EF performed the research and wrote the paper; Graham SM, Macfarlane RJ and Tsiridis EM provided significant contributions in drafting the paper and revising it critically for important intellectual content; Tsapakis EM provided expert review.
Conflict-of-interest statement: The authors confirm that there are no potential conflicts of interest. There is no financial support to declare.
Data sharing statement: None.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Correspondence to: Simon M Graham, MBChB, MRCS, Department of Trauma and Orthopaedics, the Royal Liverpool University Hospital, Prescot St, Liverpool L7 8XP, United Kingdom.
Telephone: +44-151-7062000 Fax: +44-151-7065806
Received: December 5, 2016
Peer-review started: December 6, 2016
First decision: January 16, 2017
Revised: February 8, 2017
Accepted: February 28, 2017
Article in press: March 2, 2017
Published online: May 18, 2017

To determine the existence of a common pathological link between dementia and osteoporosis through reviewing the current evidence base.


This paper reviews the current literature on osteoporosis and dementia in order to ascertain evidence of a common predisposing aetiology. A literature search of Ovid MED-LINE (1950 to June 2016) was conducted. The keywords “osteoporosis”, “osteoporotic fracture”, “dementia” and “Alzheimer’s disease” (AD) were used to determine the theoretical links with the most significant evidence base behind them. The key links were found to be vitamins D and K, calcium, thyroid disease, statins, alcohol and sex steroids. These subjects were then searched in combination with the previous terms and the resulting papers manually examined. Theoretical, in vitro and in vivo research were all used to inform this review which focuses on the most well developed theoretical common causes for dementia (predominantly Alzheimer’s type) and osteoporosis.


Dementia and osteoporosis are multifaceted disease processes with similar epidemiology and a marked increase in prevalence in elderly populations. The existence of a common link between the two has been suggested despite a lack of clear pathological overlap in our current understanding. Research to date has tended to be fragmented and relatively weak in nature with multiple confounding factors reflecting the difficulties of in vivo experimentation in the population of interest. Despite exploration of various possible mechanisms in search for a link between the two pathologies, this paper found that it is possible that these associations are coincidental due to the nature of the evidence available. One finding in this review is that prior investigation into common aetiologies has found raised amyloid beta peptide levels in osteoporotic bone tissue, with a hypothesis that amyloid beta disorders are systemic disorders resulting in differing tissue manifestations. However, our findings were that the most compelling evidence of a common yet independent aetiology lies in the APOE4 allele, which is a well-established risk for AD but also carries an independent association with fracture risk. The mechanism behind this is thought to be the reduced plasma vitamin K levels in individuals exhibiting the APOE4 allele which may be amplified by the nutritional deficiencies associated with dementia, which are known to include vitamins K and D. The vitamin theory postulates that malnutrition and reduced exposure to sunlight in patients with AD leads to vitamin deficiencies.


Robust evidence remains to be produced regarding potential links and regarding the exact aetiology of these diseases and remains relevant given the burden of dementia and osteoporosis in our ageing population. Future research into amyloid beta, APOE4 and vitamins K and D as the most promising aetiological links should be welcomed.

Keywords: Osteoporosis, Fracture, Dementia, Thyroid disease, Alzheimer’s disease, Elderly, Vitamin D, Vitamin K, Calcium, Statins, Alcohol, Sex steroids

Core tip: A potential pathological link between osteoporosis and dementia has been explored in observational studies, but there exists a lack of large scale randomised controlled trials. We hypothesise that dementia and osteoporosis have common yet independent aetiologies. The most compelling evidence lies in the APOE4 allele, a well-established risk factor for Alzheimer’s disease. APOE4 is associated with fracture, independent of dementia and falling. The mechanism behind this is postulated to be reduced plasma vitamin K levels in individuals exhibiting the APOE4 allele. This may be augmented by the nutritional deficiencies associated with dementia, known to include vitamins K and D.