But a decade ago, endocrinologist Sundeep Khosla, M.D., made another profound discovery: Estrogen regulates bone metabolism in men as well as women. Moreover, declining estrogen levels can lead to osteoporosis in aging men just as in postmenopausal women. [J. Clin. Invest. (2000)106(12), 1553-1560]. Dr. Khosla’s finding that men need estradiol, the primary form of estrogen, drew attention to male osteoporosis. Now, collaborating with other Mayo researchers, Dr. Khosla’s laboratory team is uncovering solutions.

“This finding is leading to some important changes in our diagnostic evaluation and, potentially, treatment approaches for men with osteoporosis,” Dr. Khosla says. Although many clinicians continue to focus on testosterone levels in men with symptoms of osteoporosis, “we really ought to be looking at estradiol levels in those men,” Dr. Khosla says. “Measuring estradiol levels in older men might be a useful tool to identify those at increased risk of bone loss or fractures.”

Translating basic science such as Dr Khosla’s estrogen research into patient care is a cornerstone of Mayo’s approach to medicine. Lab discoveries lead to innovative treatments; patients’ needs raise questions about cell structure and suggest improvements in imaging technology. When a disease like osteoporosis is examined from all these angles, the results are striking. “The progress in the past 10 to 15 years has been enormous,” Dr. Khosla says. “Our understanding of how bone is regulated has exploded, and out of that has come a whole host of new treatments. There’s great excitement in osteoporosis.”

Although aging men have only about one-third the fracture rate of postmenopausal women, the number of men affected is still high. About one in eight men over age 50 will suffer an osteoporotic fracture. Moreover, the consequences can be more serious in men; they are twice as likely as women to die in hospital after a hip fracture. About 20 percent of people with hip fracture die within a year of their injury.

Dr. Khosla considers his team’s findings in male osteoporosis to be some of their most significant work. After the initial discovery, the investigators wanted to learn precisely how estrogen regulates bone metabolism. They studied knockout mice in which estrogen receptors, which promote bone growth, were unable to bind to DNA. Blocking the estrogen receptors “had a very profound effect on bone,” particularly in males, Dr. Khosla says