In this study, both weight and height were positively correlated with BMD however, correlation between BMI and BMD was not established. Age and female gender increase the risk of developing both obesity and osteoporosis, which affect millions of women. In healthy adults, body weight is tightly regulated despite day-to-day variations in food intake and energy expenditure. Several environmental, nutritional, and hormonal factors appear to influence body weight. The rate of bone loss in adults reflects the interaction between genetic and environmental factors, which also influences the extent of bone acquisition during growth, known as peak bone mass. Body fat and lean mass are correlated with bone mineral density, with obesity apparently confering protection against bone loss after menopause.
The pathophysiological role of adipose tissue in skeletal homeostasis probably lies in the role that several adipokines play in bone remodeling via their effects on either bone formation or resorption. Since the demonstration that bone cells express several specific hormone receptors, the skeleton has come to be considered an endocrine target organ. Additionally, recent observations have shown that bone-derived factors, such as osteocalcin and osteopontin, may affect body weight control and glucose homeostasis, suggesting a possible role of bone tissue as an endocrine organ with the presence of a potential feedback mechanism between the skeleton and endocrine organs. Thus, the cross-talk between fat and bone likely constitutes a homoeostatic feedback system in which adipokines and molecules secreted by osteoblasts and osteoclasts represent the link of an active bone-adipose axis.
However, the mechanism(s) by which all these events occur remains unclear. Extensive data have shown that, in healthy premenopausal and postmenopausal women, total body fat is positively related to bone mineral density, an important and measurable determinant of fracture risk, that high body weight (or body mass index) is correlated with high bone mineral density, and that decreased body weight leads to bone loss. Although these data indicate that obesity exerts a protective effect on bone tissue, more recent studies have described an opposite event. In particular, although cross-sectional and longitudinal studies have shown that bone mass is positively related to body weight and body mass index, there are controversial issues as to whether lean mass or fat mass might be the most important determinant of bone mineral density.
These conflicting results suggest a complex effect of fat mass on bone tissue related to sample size, ethnicity, gender, study design, methods of statistical analysis and population structure. Nevertheless, several lines of evidence from environmental and medical interventions support an inverse correlation between fat and bone mass, ie, physical exercise increases bone mass while reducing fat mass, supplementation with calcium and vitamin D appears beneficial for the prevention of both osteoporosis and obesity, and menopause is also associated with increased fat mass, increased bone loss, and decreased lean mass.
Several potential mechanisms have been proposed to explain the complex relationship between adipose tissue and bone tissue. Fat has long been viewed as a passive energy reservoir, but since the discovery of leptin and identification of other adipose tissue-derived hormones and serum mediators, fat has come to be considered as an active endocrine organ which modulates energy homeostasis. Adipose tissue also secretes various inflammatory cytokines, including interleukin (IL)-6 and tumor necrosis factor-alpha, and altered production of these proinflammatory mediators is thought to have adverse metabolic and cardiovascular consequences. All these molecules, which include resistin, leptin, adiponectin, and IL-6, affect human energy homeostasis and may well be involved in bone metabolism, contributing to the complex relationship between adipose tissue and bone tissue. Leptin suppresses appetite, increases energy expenditure, and regulates bone remodeling, and is the most important adipocyte-derived hormone.
The effect of leptin on bone is complex, and both negative and positive actions on bone mineral density have been reported in humans. Leptin reduces food intake and increases energy expenditure by stimulating proopiomelanocortin neurons to secrete α-melanocyte-stimulating hormone, which, in addition to having an effect on obesity, might contribute to bone resorption but not bone formation. Leptin also inhibits expression of neuropeptide Y, a hypothalamus-derived peptide, essential for the regulation of food consumption, energy homeostasis, and bone remodeling. Adiponectin is another adipocyte-derived hormone which has anti-inflammatory and antiatherogenic effects, regulating energy homeostasis and bone remodeling. Human osteoblasts express adiponectin and its receptors, but both negative and positive links between adiponectin and bone mineral density have been reported. Other in vivo and in vitro studies show that adiponectin increases bone mass by suppressing osteoclastogenesis and activating osteoblastogenesis, suggesting that a rise in adiponectin levels caused by fat reduction could have a beneficial effect on bone mineral density.
Resistin increases osteoblast proliferation and cytokine release, as well as osteoclast differentiation, so the effect of resistin on bone is still unclear, and further studies are needed to understand its role better. IL-6 is a pluripotent inflammatory cytokine, released from adipocytes, adipose tissue matrix, osteoblast, and elsewhere in the body. In particular, adipose tissue accounts for onethird of circulating levels of IL-6. IL-6 is also a well recognized stimulator of osteoclastogenesis and bone resorption but some data show that IL-6 mRNA is expressed in preosteoblasts and osteoblasts, and that IL-6 stimulates osteoblast proliferation and differentiation by controlling the production of local factors,108 and it might play a role in bone formation in conditions of high bone turnover.
In addition to adipocytes, adipose tissue contains various stromal and vascular cells, including fibroblasts, vascular endothelial cells, and inflammatory cells. Adipocytes were initially thought to be the major source of adipose-derived mediators, but recent studies have shown that macrophages infiltrate adipose tissue, and that these macrophages, along with other cells that reside in the stroma, also contribute to the production and secretion of humoral mediators, particularly inflammatory cytokines. A paracrine loop involving free fatty acids and inflammatory cytokines has been postulated to establish a vicious cycle between adipocytes and macrophages, thereby propagating inflammation. Therefore, it is important to define interactions between adipocytes, osteoblasts, and stromal cells in obese subjects61.
