The neuropeptide Y-ergic system: potential therapeutic target against bone loss with obesity treatments

Obesity is no longer considered to provide protection against osteoporosis. Moreover, treatments for obesity are now suspected of reducing bone mass. With the escalating incidence of obesity, combined with increases in the frequency, duration and intensity of interventions used to combat it, we face a potential increase in health burden due to osteoporotic fractures. The neuropeptide Y-ergic system offers a potential target for the prevention and anabolic treatment of bone loss in obesity, due to its dual role in the regulation of energy homeostasis and bone mass. Although the strongest stimulation of bone mass by this system appears to occur via indirect hypothalamic pathways involving Y2 receptors (one of the five types of receptors for neuropeptide Y), Y1 receptors on osteoblasts (bone-forming cells) induce direct effects to enhance bone mass. This latter pathway may offer a suitable target for anti-osteoporotic treatment while also minimizing the risk of adverse side effects.