New research from Australia is shedding light on the role between chronic stress and depression and bone loss and an increased risk of fractures. Scientists, led by Holger Henneicke of the University of Sydney, examined the impact of chronic stress on skeletal metabolism and structure in mice, comparing a group of wild type mice with a group in which the signals of a hormone, suspected of being responsible, had been disrupted.
Stressed Males Have More Bone Loss?

Holger Henneicke said in the May 18, 2016 news release, “We know stress and depression are linked to poor bone health but not how one results in the other, so we set out to determine the role played by stress hormones, known as glucocorticoids, in the cells which synthesis bone. Eight-week-old male and female mice were exposed to chronic but mild stress. In some mice, the glucocorticoid signaling was selectively disrupted in bone-forming osteoblasts, while their littermates were left ‘wild.’”
The control group was not exposed to stress.
Dr. Henneicke continued, “After four weeks of stress exposure, the mice were examined and a portion of the spine – the L3-vertebrae – plus tibia and blood were analyzed. When compared to the non-stressed control group, the wild type mice, with normal intact stress hormone signaling, experienced a loss of bone mass in the analyzed vertebrae and a reduction in the area of the tibial cortex, as well as an increase in the activity of osteoclasts, a type of bone cell that breaks down bone tissue for maintenance and repair purposes. Meanwhile, the stressed mice whose glucocorticoid signaling had been disrupted did not experience this effect. And interestingly, this only applied to males. In stressed females, neither the vertebral nor tibial structures were affected.”
Dr. Henneicke concluded, “So in male mice, glucocorticoid signaling in osteoblasts and the subsequent activation of osteoclasts is part of what lies behind bone loss during chronic mild stress. In female mice, it is a different story altogether, chronic stress did not seem to influence bone health and we are currently looking into why not.”
Dr. Henneicke told OTW, “For me personally, the most interesting and unexpected result is the gender difference in this study. While we now have a reasonable understanding of stress-induced bone loss in male rodents, in females, we are really just at the beginning.”
Regarding any hypotheses as to why this didn’t affect females, he added, “We currently don’t have an answer to the question why female rodents are resilient to stress-induced bone loss. However, there are a number of possibilities. Receptor levels for various stress-related hormones could differ across gender for example or female sex steroids might interfere with receptor signaling. This issue will be very interesting to investigate.”

Discussion
This is a fascinating development. In my practice we've seen similar outcomes with the revised protocol. The key differentiator seems to be patient selection criteria. Has anyone else noticed the correlation with BMI thresholds?
Great point. I'd push back slightly on the conclusion, the sample size in the cited study is too small to draw population-level inferences. That said, the directional signal is compelling and worth a larger RCT.
We implemented a similar approach last year. Early results are promising but we're still gathering 12-month follow-up data. Happy to share our protocol if anyone is interested.
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