Osteoporosis and Obesity
The prevalence of both osteoporosis and obesity has been increasing over the past few decades: 55% of Americans over age 50 have weakened bones in the clinical form of osteopenia or osteoporosis (per National Osteoporosis Foundation), and nearly two-thirds of adults are either overweight or obese (Hedley et al., 2004) as indicated by the common metric body mass index. Coincidence? Maybe not. Clinical and biochemical connections between these widespread conditions have come to light as a result of detailed studies (Rosen and Bouxsein, 2006). Scientific investigation has found a correlation between body mass index and bone mineral density (BMD). BMD is a short-hand way of assessing osteoporosis or risk of osteoporosis. Scientists have also found positive correlations between an increase in adipose tissue (fat) and BMD (Reid et al., 1992; Stewart et al., 2002). Finally, eighteen genes have been identified responsible for the relationships between bone metabolism and obesity. Genetic correlations indicate that gene effects associated with increased fat mass are also associated with larger, stronger femora (Hubbard et al., 2005).
Experts suspect that the physiological link between obesity and osteoporosis occurs through leptin, a body hormone involced in homeostatic weight control (Halaas et al., 1995; Considine et al., 1996). Levels of leptin are in proportion to the quantity of adipose tissues, and thus are higher in obese individuals (Frederich et al., 1995; Hamrick et al., 2004). Researchers found that leptin affects bone density; the effect is different at different bone tissue locations. Mice raised with artificially low levels of leptin end up with shorter legs and lower bone density, and quantity of spongy bone, but the same mice have longer backs, and thicker and denser backbones.
Mice raised with lowered levels of the leptin hormone have higher levels of osteoclast activity in their bones (Hamrick et al., 2004, 2005). Most of the research in the connection between fat hormones and bones involves leptin, but there are also indications that other adipokines (cytokines produced by adipose tissue), such as adiponectin, affect bone formation and destruction (Lenchik et al., 2003; Shinoda et al., 2006; Jürimäe and Jürimäe, 2007; Richards et al., 2007). Nervous system signaling molecules like neuropeptide Y and neuromedin U affect energy metabolism in the body. They also influence bone growth and turn-over (Allison and Herzog, 2006; Panuccio et al., 2007; Sato et al., 2007).
Purely from a structural engineering standpoint, one would expect to see heavier people with thicker and stronger bones. One would predict bone morphology resulting in stronger bones just because of the increased mechanical loading in overweight individuals.
Bone cells may in turn produce cytokines and other biochemical markers that affect metabolism and obesity. It has been shown that osteocalcin directly affects the pancreas and other tissues (Lee et al., 2007). In embryonic development, bone and fat cells originate from the same progenitor cells. They develop through alternate, mutually exclusive, pathways (Wan et al., 2006) but the common origin may imply a tight, albeit not understood, relationships between skeletal and adipose tissues.
Several studies suggested that the correlation between BMD and BMI may be primarily due to environmental rather than genetic factors (Nguyen et al., 1998; Zhao et al., 2007; Greco et al., 2010). However, the correlation has been demonstrated in mice raised in identical environmental conditions, which suggests genetic factors are paramount (Cheverud et al, 2004; Reich et al., 2008). Longitudinal studies with large sample sizes, good design, and careful data analysis will be needed to conclusively show the true effect of fat mass on bone.
