Speeding up bone healing in postmenopausal females

The findings could have implications for the way fractures in women are treated in the future.

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Age-related changes affect many of the biologic processes involved in fracture healing. However, the contributions of such changes do not fully explain the poorer healing outcomes and increased morbidity reported in elderly patients.

While staggering, the gender gap is unsurprising given that more women than men have osteoporosis, a disease that weakens the bones. And yet, only recently has the scientific community shifted its focus to understanding this difference. Still, most studies have been done on male animals; hence, there is a long overdue question of why older women heal bone fractures slower than men.

A new study focusing on this found that stem cells as a potential culprit in the differing healing outcomes. Scientists next determined if there are differences in the skeletal stem cells in men versus women. They found that mouse and human skeletal stem cells are estrogen-dependent and that estrogen directly regulates bone proliferation at the stem cell level.

The team then surgically removed the ovaries from female mice to create a condition resembling menopause because the ovaries generally produce estrogen. They then put a pulverized pill directly into the wound, delivering localized estrogen to a fracture site.

In mice lacking ovaries, the scientists enhanced healing and returned skeletal stem cells to normal levels. Surprisingly, the team demonstrated that localized estrogen also restored skeletal stem cells in female mice who were naturally postmenopausal. However, estrogen delivery did not affect the fractures in male mice. Sexual dimorphism comes into play here because estrogen only affects the skeletal stem cells of females.

Wu Tsai Alliance member Charles Chan, Ph.D., an assistant professor of surgery at Stanford University and co-senior author of the paper, said, “It turns out that these male skeletal stem cells don’t express the same type of estrogen receptor as females. They express estrogen receptor 1, but not 2.”

While menopausal women’s estrogen injections can aid in bone development, systemically administered estrogen increases the risk of diseases, including breast cancer and ovarian cancer.

Chan said“Knowing that the skeletal stem cells express the receptors themselves allows us to find an alternative strategy from systemic estrogen for treating bone fractures. So now, if nana falls and breaks her hips, we can piece her pelvis back together, and locally we’ll release some estrogen to get the bone to heal.”

“The findings could one day help women who suffer from fractures and osteoporosis, as well as inform gender reaffirmation surgeries and dental implant surgeries.”

Journal Reference:

  1. Andrew, T.W., Koepke, L.S., Wang, Y. et al. Sexually dimorphic estrogen sensing in skeletal stem cells control skeletal regeneration. Nat Commun 13, 6491 (2022). DOI: 10.1038/s41467-022-34063-5
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