Flesh and Bone: New Research Upends the Conventional Wisdom About Body Weight and Bone Density in Men

June2022CoverEN

For years, obesity was thought to have the ability to thwart the occurrence of osteoporosis, especially in men. However, a new study in The Journal of Clinical Endocrinology & Metabolism shows that men with obesity could be at a higher risk for osteoporosis than previously thought.

Earlier this year, a paper entitled Fat Mass Has Negative Effects on Bone, Especially in Men: A Cross-sectional Analysis of NHANES 2011-2018” in The Journal of Clinical Endocrinology & Metabolism looked at the relationship between body composition and bone mineral density (BMD) in patients with a wide range of body mass index.

In their introduction, the authors state that while there have been several studies that show a strong positive relationship between body weight and BMD, the relationship has not been well studied in the current obesity epidemic. The authors go on to note that obesity has been linked to fractures in the humerus and other sites, and these findings “challenge conventional thinking and require a re-examination of our understanding of how weight may affect BMD.”

“While there are excellent studies looking at bone health and obesity, most studies have used body mass index as the indicator of obesity,” says one of the study’s authors, Rajesh K. Jain, MD, assistant professor of Medicine and Endocrinology Fellowship Program director at the University of Chicago Medicine. “As we know, BMI has its limitations and does not account for a person’s body composition. Studies have demonstrated that lean mass (which includes muscle mass) and fat mass have differing relationships to bone density, but the exact relationship of fat mass and bone density was not clear.”  Most previous studies have shown positive or neutral effects of body fat mass on bone health, but “have been limited due to small numbers, referral bias, or lack of racial and ethnic diversity,” says Jain.

What’s more, studies in men are scarcer and have had conflicting results. According to Jain, the main reason for this gap is that many studies chose to focus on women. “Because osteoporosis is more common in women, many research questions are asked first in women before considering men,” Jain says. “Unfortunately, this means that the discovery of novel risk factors in men may be delayed.”

Inconsistent Effects of Fat Mass

For this study, researchers analyzed the bone mineral density and body composition data of 10,814 people under 60 years old from the National Health and Nutrition Examination Survey (NHANES) 2011-2018. They found a strong positive association between lean mass and bone mineral density in both men and women. Conversely, fat mass had a moderately negative association with bone mineral density, and these effects were particularly prominent in men and those with the highest levels of fat mass. 

“It is important to ensure that associations we see in lower weight individuals are still present in obese individuals. For example, BMI has been strongly associated with bone density in many studies; however, if you look at just the subjects with BMI over 30 kg/m2 in our study, there was no relationship between BMI and bone density.” – Rajesh K. Jain, MD, assistant professor of Medicine and Endocrinology Fellowship Program director, University of Chicago Medicine, Chicago, Ill.

Jain and co-author Tamara J. Vokes, MD, write that their work contrasts with prior studies that found inconsistent effects of fat mass — positive, neutral, or slightly negative. “Furthermore, previous studies, some of which are 15 to 20 years old, may not reflect current trends in severe obesity, which has been increasing substantially in the United States and projected to worsen,” they write.

Jain tells Endocrine News that as obesity — and especially high levels of obesity — become more common, providers need to fully understand all of the health effects. “It is important to ensure that associations we see in lower weight individuals are still present in obese individuals,” he says. “For example, BMI has been strongly associated with bone density in many studies; however, if you look at just the subjects with BMI over 30 kg/m2 in our study, there was no relationship between BMI and bone density.”

A More Diverse Sampling

Jain and Vokes also point out that their study differs from previous ones in that they were able to analyze data from a diverse population. They write that very few studies have included as many men or racial and ethnic minorities, but the NHANES uses a “a complex, multistage probability sampling design to represent the US population as a whole.”

“Studying racially and ethnically diverse people is so important and one of the focuses of my research,” Jain says. “There have not been enough studies in bone health and osteoporosis looking at racially and ethnically diverse people. While we do know there are substantial differences in fracture rates by race or ethnicity, we have very little understanding about how risk factors may vary. For example, there is evidence that some of our most basic osteoporosis risk factors, such as age and body mass index, differ in Black people. I’ve also done work (also published in JCEM) looking at diabetes-related fracture risk that also demonstrated differences by race and ethnicity.”

One of the more surprising findings was that sex hormones don’t seem to fully explain the sex differences in the results. Indeed, other hormones could be playing a role, but Jain says it might still be too early to tell which ones, and what exactly they’re up to. “When we think about differences in bone health by gender, we often think about sex hormones since they play such a crucial role for bone health,” he says. “We also know that men with high levels of obesity can develop hypogonadism. We, therefore, thought it was important to investigate that as a potential cause of the sex differences. However, we did not find that sex hormones fully explained the differences we saw in bone density. More work is needed. For example, there could be effects of adipokines (released by adipose tissue) on bone.”

Obesity Is No Guarantee Against Osteoporosis

These findings may serve to shake up how things are done in the clinic. Again, the assumption among providers is that patients with obesity are at a lower risk of fracture. And for a time, that made sense; in clinical practice many of the patients with osteoporosis are underweight, and there are many studies showing an association of higher body weight or BMI with higher bone density. “However, higher body weight or BMI does not reflect a person’s body composition, which we found varied substantially even within BMI categories,” Jain says.

There are several screening recommendations in place, depending on the organization, but Jain says as far as he knows, no organization has different recommendations based on whether a patient has obesity. “For example, the United States Preventive Task Force recommends that all women over age 65 get bone density screening,” he says. “In reality, the general rate of screening is low, and more targeted screening is done for people physicians think are at risk. In general, higher BMI is associated with higher bone density so patients with obesity may be less likely to be screened.”

“There have not been enough studies in bone health and osteoporosis looking at racially and ethnically diverse people. While we do know there are substantial differences in fracture rates by race or ethnicity, we have very little understanding about how risk factors may vary. For example, there is evidence that some of our most basic osteoporosis risk factors, such as age and body mass index, differ in Black people.” – Rajesh K. Jain, MD, assistant professor of Medicine and Endocrinology Fellowship Program director, University of Chicago Medicine, Chicago, Ill.

But this study suggests that people with high body fat may be at higher risk for low bone density or fractures. Unfortunately, as of now, there is no routine way (outside of a research study) to measure body fat and appropriately identify who may be targeted for screening. “Rather than measure body fat, I would suggest clinicians consider factors that correlate with high body fat, such as the presence of diabetes, or low lean mass, such as poor performance on physical activity measures, such as grip strength,” Jain says. “These factors, in addition to their associations with body composition, are also associated with osteoporosis or fractures, and their presence should prompt clinicians to consider osteoporosis screening.” 

Jain and Vokes conclude the paper by writing that further work is necessary to understand the effects of high fat mass on the risk of fracture, devise appropriate osteoporosis screening strategies in obese patients, and determine whether negative effects of fat on bone mass are reversible with weight loss.

For now, healthcare providers should consider osteoporosis screening for patients with high body weight, especially if they have other risk factors like older age, previous fracture, family history, or steroid use, Jain says. “While higher BMI is generally associated with higher bone density,” he continues, “our study demonstrates that lean and fat mass affect bone density differently and that obesity is not a guarantee against osteoporosis.”

Bagley is the senior editor of Endocrine News. In the May issue, he wrote about the ENDO 2022 session, “Clinical Year in Review: All Things Adrenal.”

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