Downey Candice L, Young Adam, Burton Emily F, Graham Simon M, Macfarlane Robert J, Tsapakis Eva-Maria, Tsiridis Eleftherios
Candice L Downey, Emily F Burton, University of Leeds, School of Medicine, Leeds LS2 9NL, United Kingdom.
World J Orthop. 2017 May 18;8(5):412-423. doi: 10.5312/wjo.v8.i5.412.
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, and 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 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.
通过回顾当前的证据基础，确定痴呆症和骨质疏松症之间是否存在共同的病理联系。
本文回顾了当前关于骨质疏松症和痴呆症的文献，以确定是否存在共同的易患病因的证据。对Ovid MED-LINE（1950年至2016年6月）进行了文献检索。使用关键词“骨质疏松症”、“骨质疏松性骨折”、“痴呆症”和“阿尔茨海默病”（AD）来确定与其背后最显著证据基础的理论联系。发现关键联系为维生素D和K、钙、甲状腺疾病、他汀类药物、酒精和性类固醇。然后结合先前的术语对这些主题进行检索，并对所得论文进行人工检查。理论和研究都为本次综述提供了信息，该综述重点关注痴呆症（主要是阿尔茨海默病类型）和骨质疏松症最完善的理论共同病因。
痴呆症和骨质疏松症是多方面的疾病过程，具有相似的流行病学特征，在老年人群中的患病率显著增加。尽管在我们目前的理解中缺乏明确的病理重叠，但已有人提出两者之间存在共同联系。迄今为止的研究往往较为零散，本质上相对薄弱，存在多种混杂因素，这反映了在目标人群中进行实验的困难。尽管对各种可能的机制进行了探索以寻找这两种病理之间的联系，但本文发现，鉴于现有证据的性质，这些关联可能是巧合。本次综述的一个发现是，先前对共同病因的调查发现骨质疏松骨组织中淀粉样β肽水平升高，有一种假设认为淀粉样β紊乱是全身性疾病，会导致不同的组织表现。然而，我们的发现是，共同但独立病因的最有说服力的证据在于APOE4等位基因，它是AD的一个既定风险因素，但也与骨折风险存在独立关联。其背后的机制被认为是携带APOE4等位基因的个体血浆维生素K水平降低，而与痴呆症相关的营养缺乏（已知包括维生素K和D）可能会放大这种情况。维生素理论假设，AD患者的营养不良和阳光照射减少会导致维生素缺乏。
关于潜在联系以及这些疾病的确切病因，仍有待提供有力证据，鉴于痴呆症和骨质疏松症在老年人群中的负担，这一问题仍然具有相关性。未来对淀粉样β、APOE4以及维生素K和D作为最有希望的病因联系的研究应该受到欢迎。
