Age-related factor, not estrogen, key in osteoporosis, study says

A new day could be dawning in medicines understanding of the debilitating bone-loss ailment osteoporosis after researchers at the University of Arkansas for Medical Sciences reported discovering an age-related mechanism associated with the ailment.

The discovery by Dr. Stavros Manolagas and his UAMS colleagues appears to overturn the decades-old belief that the reduction of the hormone estrogen in women was the main culprit.

Instead, aging and the body's increased inability to defend against bone-damaging molecules produced through a process known as oxidative stress are most directly responsible for the bone-weakening disease, Manolagas and his team reported in an article published in the Feb. 3 issue of the journal Cell Metabolism.

This age-related mechanism may be behind other age-related diseases.

Based on its research, the UAMS team has concluded that age weakens the defenses against oxidative stress. In particular, an age-related loss of certain proteins, the FoxOclass, which defend against oxidative stress increase the risk of osteoporosis.

A reduction in estrogen may simply further decrease the molecular defenses against oxidative stress, rather than being the main causal factor, they say.

"We feel like we have turned a page in our understanding of osteoporosis," said Manolagas. "This emerging evidence provides a paradigm shift from the estrogen-centric view of what causes osteoporosis to one in which these age-related mechanisms are the main protagonists and other changes - including the reduction of estrogen - accentuate them."

The FoxO proteins defend against oxidative stress. With age, however, the oxidative stress begins to overwhelm the defense mechanisms, according to Manolagas.

"Now we will look for what specifically causes the defense mechanisms against oxidative stress to fail over time," he said.