Effects of obesity on bone metabolism

• Main Author: Cao Jay J
• Format: Article
• Language: English
• Published: BMC 2011-06-01
• Series: Journal of Orthopaedic Surgery and Research
• Subjects: bone; fat; obesity; osteoporosis; inflammation
• Online Access: http://www.josr-online.com/content/6/1/30

<p>Abstract</p> <p>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.</p> <p>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 <abbrgrp><abbr bid="B1">1</abbr></abbrgrp>. The rates of obesity rates have doubled since 1980 <abbrgrp><abbr bid="B2">2</abbr></abbrgrp> and as of 2007, 33% of men and 35% of women in the US are obese <abbrgrp><abbr bid="B3">3</abbr></abbrgrp>. Obesity is positively associated to many chronic disorders such as hypertension, dyslipidemia, type 2 diabetes mellitus, coronary heart disease, and certain cancers <abbrgrp><abbr bid="B4">4</abbr><abbr bid="B5">5</abbr><abbr bid="B6">6</abbr></abbrgrp>. It is estimated that the direct medical cost associated with obesity in the United States is ~$100 billion per year <abbrgrp><abbr bid="B7">7</abbr></abbrgrp>.</p> <p>Bone mass and strength decrease during adulthood, especially in women after menopause <abbrgrp><abbr bid="B8">8</abbr></abbrgrp>. 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 <abbrgrp><abbr bid="B9">9</abbr></abbrgrp>. In 2001, osteoporosis alone accounted for some $17 billion in direct annual healthcare expenditure.</p> <p>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 <abbrgrp><abbr bid="B10">10</abbr></abbrgrp> and agents inhibiting adipogenesis stimulated osteoblast differentiation <abbrgrp><abbr bid="B11">11</abbr><abbr bid="B12">12</abbr><abbr bid="B13">13</abbr></abbrgrp> and vice versa, those inhibiting osteoblastogenesis increased adipogenesis <abbrgrp><abbr bid="B14">14</abbr></abbrgrp>. Second, decreased bone marrow osteoblastogenesis with aging is usually accompanied with increased marrow adipogenesis <abbrgrp><abbr bid="B15">15</abbr><abbr bid="B16">16</abbr></abbrgrp>. Third, chronic use of steroid hormone, such as glucocorticoid, results in obesity accompanied by rapid bone loss <abbrgrp><abbr bid="B17">17</abbr><abbr bid="B18">18</abbr></abbrgrp>. Fourth, both obesity and osteoporosis are associated with elevated oxidative stress and increased production of proinflammatory cytokines <abbrgrp><abbr bid="B19">19</abbr><abbr bid="B20">20</abbr></abbrgrp>. At present, the mechanisms for the effects of obesity on bone metabolism are not well defined and will be the focus of this review.</p>