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For Megan Roche, MD, attending this year’s Western States Endurance Run was about more than watching history unfold. The five-time USATF trail national champion and epidemiology researcher at Stanford University was also there to collect data from athletes participating in the 100-mile race for a study she’s authoring with Emily Kraus, MD, a clinical assistant professor at Stanford Children’s Orthopedic and Sports Medicine Center.
According to Dr. Kraus, the study, which is funded by the Western States Research Foundation, aims to enhance the understanding of the ultra-endurance population, both males and females, specifically with regard to history of bone stress injuries and injury history by looking at baseline bone mineral density and bone health and values. Distance runners are at the highest risk for bone stress injuries, which are a common injury that can leave them sidelined or unable to train or compete for many weeks or months, depending on the type or severity of the injury. Drs. Roche and Kraus were inspired to pursue this research not just because research in ultra-athletes is currently lacking, but also because it’s lacking for female athletes in general.
“We still need a lot of research to better understand risk stratification and risk profile when it comes to genetic risks, but even just with the relationship of nutrition, labs, and training volume, we’re really trying to push those research efforts on female athletes of all ages and show how you can change behaviors before those risks lead to injury,” Dr. Kraus says. “Research in the ultramarathon population is not as extensively studied as in the NCAA population or even the high school population. Getting these first two years of results is helpful in terms of identifying potential areas of concern.”
Drs. Roche and Kraus’s study methods included a pre-race survey to examine the prevalence of disordered eating, bone stress injuries, menstrual dysfunction in women, and training volume; as well as genetic testing via a saliva test, a DEXA scan to test the bone mineral density of the lumbar spine, femoral neck and total hip, and a lab draw carried out during the race weekend with the assistance of InsideTracker, a company that uses a comprehensive blood test and a detailed analysis of 12 key biomarkers to inform factors from nutrition and diet to workouts and injury prevention.
“We tried to get the athletes to do fasting lab draws, if possible, and we assessed estradiol and testosterone, both free and total, and ferritin, a measure of iron stores and vitamin D,” Dr. Kraus explains. “Our thought was to look at both males and females for both of those, because there can be relationships with testosterone levels, even just lower on the spectrum of low in female athletes with hormonal suppression due to low energy availability.”
Findings show a prevalence of disordered eating, or “low energy availability”
Drs. Roche and Kraus currently have study results from the last two years, which they’d been building off leading up to this year’s race. The study followed 83 men and 40 women (both professional and recreational runners of varying levels, all of whom participated in this year’s race) over the course of two years in 2018 and 2019, which Roche noted is fairly consistent with the ratio of men to women in the actual racing field.
In ultramarathon runners, the prevalence Drs. Kraus and Roche found a lifetime history of bone stress injury of around 24%. This made them eager to understand if the risk factors for bone stress injury and ultramarathon runners were similar to risk factors and kind of other runners of different populations. For female runners, such injuries are often closely tied to the female athlete triad, which is defined as three interrelated components: low energy availability with or without disordered eating or an eating disorder; menstrual irregularities or irregular periods; and low bone mineral density or history of bone stress injury.
Additionally, around 48% of female participants were using some form of hormonal contraception, and about 38% had a history of a stress fracture or bone stress injury compared to 20% in males. With regard to eating disorders and disordered eating, the study referred to these behaviors as “low energy availability,” emphasizing that it can be difficult to distinguish the true intention of some of these behaviors within their reported history. However, about 52.5% of female subjects self-reported in their questionnaire that they were trying to lose weight for performance. Two-thirds of those athletes had moderate- to high-risk for low energy availability, which Dr. Kraus noted was significant, as it amounted to 25 of the 40 female athletes.
“This goes back to the importance of really emphasizing nutrition and fueling as part of the training, and with this population, just like the entire running population, is an important component to factor into coaching and training recommendations,” Dr. Kraus says.
“Sometimes we see a lag in an athlete’s energy availability and how that impacts the body, both hormonally and bone mineral density-wise, and so sometimes, an athlete may not be fueling their body appropriately for a couple of months or for even a couple of years, and it takes a little bit of time to see those impacts on the body,” Dr. Roche adds. “That’s why it’s really important to catch athletes in this early stage of low energy availability, because you can prevent those downstream consequences from occurring.”
In year one and year two, Drs. Kraus and Roche did find some relationships between sex hormone levels and bone mineral density in females, though Dr. Kraus noted that it’s hard to assess stress fracture risk on this spectrum.
“I think we would need quite a higher number of runners to really see those types of trends, but basically the higher those hormone levels, the higher the bone mineral density,” she says. “Sometimes there can be blood or hormone level changes that may be influencing the bone mineral density before we’re really seeing the extent or severity of low bone mineral density that sometimes we see kind of at later stages.”
Dr. Kraus also noted that while many people would expect runners to have higher than normal bone mineral density, it’s important to consider these values are compared to age and sex-matched controls.
“The thing that I found most interesting from this was kind of the discrepancy between the rate of bone stress injury and the rate of low bone mineral density in female athletes,” Dr. Roche adds. “We found a higher percentage of athletes had a stress fracture compared to the percentage who had low bone mineral density. This highlights the fact that stress fractures and bone stress injuries are so multifactorial, which is why it’s helpful to look at other hormonal profiles to look at low energy availability, along with looking at genetic predictors, because it’s really just not bone mineral density that’s a risk factor at the end of the day.
“While this makes the picture a little bit more complicated, I think it’s helpful when thinking about coaching or training recommendations for athletes, because it’s really about considering so many different unique considerations for each athlete.”
Tests can be helpful for nailing low values, preventing injuries
Dr. Kraus also noted that study results showed average ferritin levels of 30.8 and 31.3 for vitamin D in females, which she would consider to be low.
“What a lab might tell you is normal in the general population might result in athletes being fairly symptomatic,” she says. “It’s defined as sufficient, in more clinical terms, but I think in an athlete who’s engaging in regular or higher intensity physical activity, those levels should be optimized.”
Dr. Roche cited this difference in how a lab approaches blood tests vs. how an athlete-minded company views them as a big reason she likes working with InsideTracker for testing endurance runners.
“I think sometimes athletes will go to a physician who may not have a background in running or athletics, and so they may see these values and say and tell an athlete they’re OK and cleared,” Dr. Roche adds. “But InsideTracker really helps break down what’s optimized, versus what may be considered low-normal and what may be considered low, and it’s very helpful to go onto their platform and kind of have that range and to see where athletes should be falling, as opposed to just the general reference ranges for the regular population.”
Dr. Kraus also highlighted that lab results are communicated to the participants in the study, with many finding it valuable to understand their health metrics and overall health profile, as it relates to bone health.
“One female athlete in particular got some of the results and had a very low iron level, and she noted that it changed her whole approach and philosophy toward training and nutrition, which helped to improve her life and training experience,” she says. “These are some of the benefits athletes may not be aware of, they may not even realize that these values are so low or that maybe their bone health is suboptimal per the DEXA scan, and they can really kind of make more proactive changes.”
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What’s next for this research?
Drs. Roche and Kraus are also studying a risk score that looks at genetic markers for bone mineral density and bone stress injury. They are working with Stuart Kim, another scientist at Stanford who has taken these genetic markers from a larger biobank and has validated them in other populations, but not the ultra-marathon population.
“Before this year, we only had 40 female athletes to do the analysis on, and so we’ll have a lot more information after this year’s results,” Dr. Roche says. “After this year’s genetic analysis is done, our goal is really to just to get a complete picture of bone stress injury risk, and having the genetic component to explain the percentage of an athlete’s overall risk profile.”
Dr. Kraus noted that it will take about four to six weeks to get this year’s results back, followed by a couple of months to gather and organize data before writing and submitting their manuscript. Some of their preliminary research has been accepted for publication in the Clinical Journal of Sports Medicine to tentatively be published later this summer. They will also be submitting their data to organizations such as the American College of Sports Medicine or the American Medical Society of Sports Medicine.
What can female athletes make of this data?
As far as what other athletes can glean from the study, Dr. Kraus hopes they take into account that training for these races is more than just logging the miles.
“I would hope that they would factor in their nutrition, and not just how much they’re eating, but what they’re putting into their body,” she says. “A big takeaway is the importance of optimal nutrition, especially in the female athlete, and how that can affect both bone health and hormones.”
“For me, it really gets down to the sheer prevalence we found of athletes struggling with disordered eating, whether that’s intentional or something that they don’t even know is going on and was totally unintentional,” Dr. Roche says. “I think athletes should keep in mind that when competing in ultramarathons like this, being attentive to nutrition is really important, and doing that through a care team can be really powerful, whether that’s with [a registered dietitian], a physician or someone who can replicate the labs and processes we did. I also hope more athletes will just be more willing to talk about it, to seek care, talk to coaches about it, and just make this a more normal conversation, given how prevalent it is in the ultra-marathon population.”