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Loss Of Lean Mass, But Not Fat Mass, Tied to Fracture Risk

ORLANDO — Prior loss in total body lean mass, but not fat mass, could be a predictor for future fracture, a researcher said here.

In a group of close to 10,000 predominantly female patients, reductions in total body lean mass were associated with a significantly higher risk for fracture, such that each standard deviation in lean mass loss was associated with between 10% and 13% increased risk for major osteoporosis fractures after adjusting for height loss, fracture risk assessment tool (FRAX) scores with and without bone density, and competing mortality, reported William Leslie, MD, of the University of Manitoba in Canada.

The association was even stronger when looking at hip fracture, with between 29% and 38% increased risk for hip fracture for each standard deviation in lean mass loss, he said during a presentation at the American Society for Bone and Mineral Research annual meeting.

“This [fracture risk] is independent of other risk factors including height loss and increased mortality that are associated with reductions in both lean and fat mass. Overall, this is consistent with the hypothesis that muscle loss adversely impacts skeletal health and fractures,” Leslie said.

In contrast, total body fat mass loss showed no significant increased risk for either major osteoporosis or hip fracture, he reported.

Mortality from tissue loss was greater in patients with prior total body lean mass loss and total body fat mass loss independent of height loss and bone mineral density (BMD), such that each standard deviation reduction was associated with an 8% and 15% increased risk, respectively, he said.

Leslie said the widely-used FRAX tool considers BMI measurements derived from height and weight as baseline measures, but does not look at height and weight over time. This analysis was an attempt to assess the longitudinal effects of two components of weight loss, he said.

The study used an estimated body composition measure based on weight, sex, and percent fat measured from the abdomen and hip dual energy x-ray absorptiometry (DEXA), which Leslie’s group determined was fairly accurate for both lean mass and body fat as shown with an R2 value of 0.84 and 0.94, respectively.

However, DEXA is not a direct measure of muscle mass and accounts for everything that is not fat or bone in the body, like skin, water, or fibrotic tissue, said Peggy Cawthon, PhD, MPH, of the University of California San Francisco, who was not involved in the study. Although DEXA is commonly — and correctly — used to diagnose osteoporosis, a growing body of literature has put into question its accuracy in predicting muscle, she said.

“The concern is, is it muscle, or is it just weight loss alone, or is it some other change we’re not capturing that is not muscle itself?” Cawthon told MedPage Today.

“The reason that’s important is, it would have much different clinical recommendations,” she explained. “Either maintain muscle or don’t lose weight. Those are different pathways for people to take and different causal mechanisms.”

Leslie said the lack of a direct measure for body composition was a study limitation, although he noted that reductions in weight and lean/fat mass are co-determined.

For the study, the authors measured the body composition of adults, ages ≥40, who had two spin-hip assessments in the DEXA Registry and Repository at least a year apart. This was then linked with hospitalizations, physician services, and pharmacy use.

In total, a cohort of 9,694 individuals “fairly typical” of those seen in the clinic for BMD testing were included, Leslie said. They were a mean age of 67, almost all women (95%), and predominantly Caucasian. The group had an average baseline height of 161 cm and average weight of 67 kg (about 148 lbs). The cohort’s FRAX probabilities with BMD were in the modest to high range for major osteoporosis fracture (12%) and hip fracture (3.08%), Leslie said.

Overall, the group lost a mean 0.53 cm in height and 0.61 kg in lean mass, while they gained a mean 0.05 kg in fat mass, with all weight loss occurring before the index date. There were 692 major osteoporosis fractures and 194 hip fractures to occur across a mean follow-up time of 6 years.

Leslie said they depended on the validity of administrative data to diagnose fractures, which is another study limitation. There also was a potential for referral bias, he said, since this was a clinical population. However, the group avoided recall bias because the data was extracted directly from population-based registries, he said.

“If we’re looking for things that work in clinical practice, this was developed and evaluated in clinical practice,” he said. “This is representative of the patients many of us see in our routine work.”

Leslie disclosed no relevant relationships with industry.