Effects of obesity on bone metabolism.
Effects of obesity on bone metabolism.
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DOI：
10.1186/1749-799x-6-30
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发表时间：
2011-06-15
影响因子：
2.6
通讯作者：
Cao JJ
中科院分区：
文献类型：
--
作者：
Cao JJ
肥胖传统上被认为有益于骨骼健康，因为体重赋予的机械负荷对骨形成的积极影响是公认的，尽管它是许多其他慢性健康疾病的风险因素。虽然身体质量对骨形成有积极的影响，但肥胖或过度脂肪积累产生的质量对骨骼是否有益仍存在争议。肥胖和骨骼之间的病理生理关系是复杂的，并且仍然是一个活跃的研究领域。流行病学和动物研究的最新数据有力地支持了脂肪堆积对骨量有害的观点。据我们所知，肥胖可能通过几种机制影响骨代谢。由于脂肪细胞和成骨细胞都来自共同的多潜能间充质干细胞，肥胖可能会增加脂肪细胞的分化和脂肪堆积，而减少成骨细胞的分化和骨形成。肥胖与慢性炎症有关。肥胖时循环和组织促炎性细胞因子的增加可能通过改变核因子受体激活剂RANK/RANK配体/护骨素途径促进破骨细胞活性和骨吸收。此外，肥胖时脂肪细胞过度分泌瘦素和/或减少脂联素的产生，可能直接影响骨形成，或通过上调促炎细胞因子的产生间接影响骨吸收。最后，高脂肪摄入可能会干扰肠道钙的吸收，从而降低骨形成所需的钙的利用率。在分子水平上解开脂肪和骨代谢之间的关系可能有助于我们开发治疗肥胖症和骨质疏松症的药物。肥胖的定义是身体质量指数≥为30公斤/平方米，是一种身体脂肪过多积累到对健康不利的程度的情况。自1980年以来，肥胖率翻了一番，截至2007年，美国33%的男性和35%的女性肥胖。肥胖与许多慢性疾病呈正相关，如高血压、血脂异常、2型糖尿病、冠心病和某些癌症。据估计，在美国，每年与肥胖有关的直接医疗费用约为1000亿美元。成年期的骨量和强度会下降，尤其是绝经后的女性。这些变化可能最终导致骨质疏松症，骨质疏松症是一种以骨量减少和微结构恶化为特征的疾病，导致骨折风险增加。据估计，50岁以上的美国人中约有1000万人患有骨质疏松症，另有3400万人面临罹患骨质疏松症的风险。2001年，仅骨质疏松症一项就占每年直接保健支出约170亿美元。有几条证据表明，肥胖和骨代谢是相互关联的。首先，成骨细胞(骨形成细胞)和脂肪细胞(储能细胞)都来源于共同的间充质干细胞，抑制脂肪生成的药物促进成骨细胞分化，反之亦然，抑制成骨细胞生成的药物促进脂肪生成。第二，随着年龄的增长，骨髓成骨细胞生成减少，通常伴随着骨髓脂肪生成的增加。第三，长期使用类固醇激素，如糖皮质激素，会导致肥胖并伴有迅速的骨质流失。第四，肥胖和骨质疏松症都与氧化应激升高和促炎细胞因子的产生增加有关。目前，肥胖对骨代谢影响的机制尚不清楚，将成为本文综述的重点。
Obesity is traditionally viewed to be beneficial to bone health because of well-established positive effect of mechanical loading conferred by body weight on bone formation, despite being a risk factor for many other chronic health disorders. Although body mass has a positive effect on bone formation, whether the mass derived from an obesity condition or excessive fat accumulation is beneficial to bone remains controversial. The underline pathophysiological relationship between obesity and bone is complex and continues to be an active research area. Recent data from epidemiological and animal studies strongly support that fat accumulation is detrimental to bone mass. To our knowledge, obesity possibly affects bone metabolism through several mechanisms. Because both adipocytes and osteoblasts are derived from a common multipotential mesenchymal stem cell, obesity may increase adipocyte differentiation and fat accumulation while decrease osteoblast differentiation and bone formation. Obesity is associated with chronic inflammation. The increased circulating and tissue proinflammatory cytokines in obesity may promote osteoclast activity and bone resorption through modifying the receptor activator of NF-κB (RANK)/RANK ligand/osteoprotegerin pathway. Furthermore, the excessive secretion of leptin and/or decreased production of adiponectin by adipocytes in obesity may either directly affect bone formation or indirectly affect bone resorption through up-regulated proinflammatory cytokine production. Finally, high-fat intake may interfere with intestinal calcium absorption and therefore decrease calcium availability for bone formation. Unraveling the relationship between fat and bone metabolism at molecular level may help us to develop therapeutic agents to prevent or treat both obesity and osteoporosis. Obesity, defined as having a body mass index ≥ 30 kg/m2, is a condition in which excessive body fat accumulates to a degree that adversely affects health. The rates of obesity rates have doubled since 1980 and as of 2007, 33% of men and 35% of women in the US are obese. Obesity is positively associated to many chronic disorders such as hypertension, dyslipidemia, type 2 diabetes mellitus, coronary heart disease, and certain cancers. It is estimated that the direct medical cost associated with obesity in the United States is ~$100 billion per year. Bone mass and strength decrease during adulthood, especially in women after menopause. These changes can culminate in osteoporosis, a disease characterized by low bone mass and microarchitectural deterioration resulting in increased bone fracture risk. It is estimated that there are about 10 million Americans over the age of 50 who have osteoporosis while another 34 million people are at risk of developing the disease. In 2001, osteoporosis alone accounted for some $17 billion in direct annual healthcare expenditure. Several lines of evidence suggest that obesity and bone metabolism are interrelated. First, both osteoblasts (bone forming cells) and adipocytes (energy storing cells) are derived from a common mesenchymal stem cell and agents inhibiting adipogenesis stimulated osteoblast differentiation and vice versa, those inhibiting osteoblastogenesis increased adipogenesis. Second, decreased bone marrow osteoblastogenesis with aging is usually accompanied with increased marrow adipogenesis. Third, chronic use of steroid hormone, such as glucocorticoid, results in obesity accompanied by rapid bone loss. Fourth, both obesity and osteoporosis are associated with elevated oxidative stress and increased production of proinflammatory cytokines. At present, the mechanisms for the effects of obesity on bone metabolism are not well defined and will be the focus of this review.