Karsenty's team further found that the bone resorption process creates an acidic environment that converts osteocalcin into an "active" form, which can escape bone and enter circulation. Karsenty calls this process a "feed-forward" loop, where insulin stimulates the production of osteocalcin, which in turn stimulates more insulin production. His team's findings suggest that the bone resorptive process is necessary to further stimulate of insulin generation.
"The significance of this is that bone is an integrated part of how whole body glucose equilibrium is regulated. Drugs that inhibit bone resorption [which are commonly used to treat osteoporosis] may, in certain patients, favor glucose intolerance," Karsenty says. He adds that this is a concern that also needs to be addressed in future studies.
Clifford Rosen, senior scientist at Maine Medical Center Research Institute who was not involved with either study, says the new findings have "huge implications" and "bring the skeleton into the metabolic arena." He points out that mice have very high metabolic rates, however, so future studies will need to address whether this loop exists in humans. Also, glucose is a major stimulator of insulin, and other compounds in the body can stimulate its production as well, so where in the hierarchy of metabolic regulation the skeleton fits in is not yet clear.
Together, the studies suggest that bone plays a part in energy expenditure, Clemens says. "It's a part we missed before. We knew that muscle and fat played a role in metabolism, but we didn't think of bone as a true metabolic organ. This puts the skeleton, specifically bone cells, in control of body composition, through insulin," he adds.