$2.2 million awarded to study loss of bone strength in menopausal women     

An investigative team featuring U-M faculty members has been awarded a $2.2 million grant from the National Institutes for Health to identify key features that identify women most likely to lose bone strength during the menopausal transition.

The team is made up of Karl Jepsen, Ph.D., from the Michigan Medicine Department of Orthopaedic Surgery; Carrie Karvonen-Gutierrez and Sioban Harlow from the Center for Midlife Science in the U-M School of Public Health; and Arun Karlamangla and Gail Greendale from UCLA.

“We have identified a very simple trait – bone width – that has shown tremendous promise,” said Jepsen.

Preliminary studies show that women with narrow bones do not lose much bone mass, and actually gain bone on the outer surface, during menopause, which is a critical window in a woman’s life that has a profound impact on her bone health. Thus, women with narrow bones may be maintaining or even increasing their bone strength during the midlife.

In contrast, women with wide bones show tremendous loss of bone mass but minimal outer bone expansion. This means women with wide bones may be losing bone strength earlier and faster than women with narrow bones.

The grant will examine changes in bone structure and mass over 14 years in women as they transition through menopause. By combining engineering, imaging and epidemiological expertise, the team aims to improve understanding of how these different structural and mass changes affect bone strength.

This grant will leverage existing and new information from two epidemiologic cohort studies, the Michigan Bone Health and Metabolism Study and the Michigan site of the Study of Women’s Health Across the Nation. Both studies have more than 20 years of imaging data available on participants prior to, during, and after the menopausal transition, thus providing the information needed to answer the key questions.

The current clinical paradigm involves waiting until a woman is 65 years of age or older and has lost significant bone mass and strength before beginning treatment. This grant has the potential to make a scientific breakthrough and advance clinical care by providing a systematic way to identify subgroups of women most at risk of bone loss, and consequent risk of later life fracturing, and to do so early in midlife and before significant loss of bone strength.

Moving the diagnostic window up 20-30 years will allow women to maintain their strength as long as possible. The challenge of identifying women early in life is that their bones are generally quite healthy and no clinical measures currently exist that can predict future fractures prior to the menopausal transition.