Breakdown of bone keeps blood sugar in check, study finds

The destruction of old bone during normal skeletal regrowth plays an important role in regulating blood sugar, according to researchers with Columbia University Medical Center.

The discovery suggests that diabetes in some patients may develop from changes in the skeleton, and drugs designed to stimulate the bone-insulin pathway may lead to better drugs for type 2 diabetes.

The study, published in Cell, affirms that resorption – the regular and lifelong process through which old bone is destroyed to aid in the process of new bone creation – is necessary to maintain a healthy level of glucose in the blood and acts to stimulate the release of insulin into the bloodstream. Furthermore, the study says, resorption helps improve the uptake of glucose by cells in the entire body.

“This research has important implications for both diabetes and osteoporosis patients,” stated Gerard Karsenty, MD, PhD, study leader, in a press release. “First, this research shows that osteocalcin is involved in diabetes onset; secondly, bone may become a new target in the treatment of type 2 diabetes … as it appears to contribute strongly to glucose intolerance; and, finally, osteocalcin could become a treatment for type 2 diabetes.”

Osteocalcin’s importance

The release noted that the first clue the skeleton may have an important role in regulating blood glucose came in 2007, when Karsenty discovered that osteocalcin can regulate glucose levels.

Karsenty’s new study reveals that osteocalcin cannot work until cells that degrade bone start working and begin the resorption process.

“Remarkably, insulin was discovered to favor bone resorption,” Karsenty stated in the release. “Hence, in a feed-forward loop it favors the activation of osteocalcin, which in turn favors insulin synthesis and secretion. Insulin is a street-smart molecule that takes advantage of the functional interplay between bone resorption and osteocalcin, to turn-on the secretion and synthesis of more insulin.”

Osteoporosis in a new light

The study’s findings strengthen the idea that diabetes could be treated by increasing the level of osteocalcin in the body. The researchers also suggested that since most osteoporosis drugs work by inhibiting bone resorption, those drugs may decrease the activation of osteocalcin and cause glucose intolerance in some patients.

“… for people with osteoporosis, the concern is that a common treatment, bisphosphonates […] could push someone with borderline glucose intolerance into full-fledged disease onset,” Karsenty stated. “Although, more research is needed to study this further.”

Reference:
Ferron M, Wei J, Yoshizawa T, et al. Insulin signaling in osteoblasts integrates bone remodeling and energy metabolism. Cell. July 23, 2010. 10.1016/j.cell.2010.06.003