Contrary to conventional clinical wisdom, greater body fat is associated with lower bone mineral density (BMD), particularly in men, an analysis of data from a large, nationally representative sample has found.
Much previous research has suggested that obesity protects against fractures and loss of BMD for a variety of reasons, including the beneficial effects of weight-bearing on the skeleton and hormonal factors linked to body fat. But the new findings should prompt a reconsideration of the relationship between obesity and fracture risk, according to the investigators, whose study appears in the latest issue of the Journal of Clinical Endocrinology & Metabolism.
"While higher BMI [body mass index] is generally associated with higher bone density, our study demonstrates that lean and fat mass affect bone density differently and that obesity is not a guarantee against osteoporosis," Rajesh K. Jain, MD, of the University of Chicago, Illinois, told Medscape Medical News.
Jain and a colleague, Tamara Vokes, MD, used multivariant modeling to examine the relationship between BMD and body composition of 10,814 men and women aged 20-59 years from the National Health and Nutrition Examination Survey (NHANES) 2011-2018. All underwent total body DXA scans.
Participants were stratified into sex-specific quartiles based on lean mass index (LMI; lean mass divided by height squared) and fat mass index (FMI; fat mass divided by height squared). Lean mass had a strong positive association with bone density, whereas fat mass had a moderate negative effect, the researchers found.
An additional kg/m2 of FMI was associated with a 0.10 lower T-score, the number of standard deviations from the expected bone density of a young adult (P < .001). The negative effect was greater in men, who had a 0.13 lower T-score per additional 1 kg/m2 of FMI compared with 0.08 lower in women (P < .001). The effect was most pronounced in people in the highest FMI quartile.
Body composition is not a routine clinical measurement, Jain and Vokes note. Prior studies of the effect of body composition on bone density have been limited by small patient numbers, referral bias, lack of racial or ethnic diversity, and the use of estimates rather than true measures of fat and lean tissue. NHANES is designed to mirror the US population.
The researchers say when it comes to patients with obesity, the findings "should not dissuade clinicians from assessing bone density, particularly if other risk factors are present."
Useful Clinical Proxies for Body Composition
Clinicians have no routine way to measure body composition in an office setting. As a result, Jain advised clinicians to look at factors that correlate with high body fat, such as the presence of diabetes, or with low lean mass, such as poor performance on physical activity measures like grip strength, when deciding whether to consider osteoporosis screening. Patients with obesity should undergo recommended bone density screening, especially if they have other risk factors such as older age, previous fracture, steroid use, or a family history of fracture, he said.
Although some extra weight may have a beneficial loading effect, too much extra weight can lead to metabolic problems and restrict movement, according to Rodrigo J. Valderrábano, MD, medical director of clinical research for the Research Program in Men's Health: Aging and Metabolism, Brigham and Women's Hospital in Boston, Massachusetts. "There's a general sense that the extra weight is only good for your bones if you can carry it around," said Valderrábano, who was not involved in the study.
More research is needed to understand why fat affects men and women differently, Jain noted. The researchers found that testosterone and estradiol values did not fully explain the variation.
Adipokines released by fat cells may be important in driving bone loss but were not measured in the study, Peter R. Ebeling, MD, president of the American Society of Bone and Mineral Research, told Medscape Medical News. Distribution of fractures in obesity suggests that a high FMI may preferentially affect cortical bone instead of trabecular bone, but further studies using high-resolution peripheral quantitative CT are required to confirm the difference, Ebeling said.
Ebeling, who was not involved in the new study, agreed that the positive relationship between BMI and BMD has led to false reassurance that people with obesity may be protected from fragility fractures. "The take-home message for clinicians is that we should not neglect bone health in our patients with obesity, both male and female," he said.
Jain has reported receiving grant support from the Amgen Foundation and being a consultant for Radius Health. Vokes has reported being an investigator, consultant, and speaker for Radius Health, investigator and consultant for Takeda Pharmaceutical, and investigator for Ascendis Pharma. Valderrábano and Ebeling have reported no relevant financial relationships.
Mary Chris Jaklevic is a healthcare journalist based in the Midwest.
J Clin Endocrinol Metab. Published online February 10, 2022. Abstract
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