The obesity of bone

Abstract

During the last decades, obesity and osteoporosis have become important global health problems, and the belief that obesity is protective against osteoporosis has recently come into question. In fact, some recent epidemiologic and clinical studies have shown that a high level of fat mass might be a risk factor for osteoporosis and fragility fractures. Several potential mechanisms have been proposed to explain the complex relationship between adipose tissue and bone. Indeed, adipose tissue secretes various molecules, named adipokines, which are thought to have effects on metabolic, skeletal and cardiovascular systems. Moreover, fat tissue is one of the major sources of aromatase, an enzyme that synthesizes estrogens from androgen precursors, hormones that play a pivotal role in the maintenance of skeletal homeostasis, protecting against osteoporosis. Moreover, bone cells express several specific hormone receptors and recent observations have shown that bone-derived factors, such as osteocalcin and osteopontin, affect body weight control and glucose homeostasis. Thus, the skeleton is considered an endocrine target organ and an endocrine organ itself, likely influencing other organs as well. Finally, adipocytes and osteoblasts originate from a common progenitor, a pluripotential mesenchymal stem cell, which has an equal propensity for differentiation into adipocytes or osteoblasts (or other lines) under the influence of several cell-derived transcription factors. This review will highlight recent insights into the relationship between fat and bone, evaluating both potential positive and negative influences between adipose and bone tissue. It will also focus on the hypothesis that osteoporosis might be considered the obesity of bone.

Keywords: adipocyte; adipokines; bone-derived factors; fat bone marrow; mesenchymal stem cell; obesity; osteoblast; osteoporosis.

Figure 1.

Interaction between adipose and skeletal tissue. Adipocytes are a source of bioactive molecules (adipokines) that act in either a paracrine or endocrine manner to modulate insulin sensitivity locally as well as in the liver and skeletal muscle. Adipose tissue is also a source of inflammatory mediators. Thus, adipose tissue promotes atherosclerosis through a number of pathologic mechanisms. IGF, insulin-like growth factor; IL, interleukin; OPN, osteopontin; TNF, tumor necrosis factor.