How Glucocorticoids Can Change Fat Mass and Redistribution

For nearly seven decades, glucocorticoid treatment has been a common therapy for rheumatoid arthritis patients. It’s popular for other rheumatic conditions, as well, because it’s cost effective and offers strong anti-inflammatory and immunosuppressive effects. But, awareness of the negative effects is growing.

Glucocorticoids can have detrimental impacts:  osteoporosis, hyperglycemia, diabetes, cardiovascular disease and infections. Weight gain, including a red, round face, abdominal obesity with thin limbs, fat pad growth around the neck and back are also common. This weight increase, called the Cushingoid appearance, has been identified for decades and shows how glucocorticoids can impact fat metabolism. But, to date, there’s been little knowledge about how glucocorticoids can change fat mass and redistribution.

Consequently, understanding has also been minimal about the overall combination effect of rheumatoid arthritis and glucocorticoid treatments on body composition. While healthy body compositions have lower proportional body fat and higher proportional fat free mass, obesity increases the risk of high blood pressure, high cholesterol, diabetes, and cardiovascular disease.

To investigate these effects, Nicole P.C. Konijn from the Department of Rheumatology in the Amsterdam Rheumatology and Immunology Center and VU University Medical Center and colleagues conducted a study, published in Rheumatology, on the short-term effects of two high dose, step down prednisolone regimens on body composition in early rheumatoid arthritis patients. In turn, two international glucocorticoid experts from the Department of Rheumatology and Clinical Immunology at Germany’s Carité University Medicine - Frank Buttgereit and Gerd R. Burmester - analyzed the research and published a commentary in Nature Reviews.

Rheumatoid arthritis and the associated chronic inflammation affects between 0.5 percent and 1.0 percent of adults. The joint pain and stiffness associated with the condition is often attributed to a night-time rise of proteins, called cytokines, and hormones in the blood. In particular, these patients see a rise in pro-inflammatory cytokines, such as interleukin-6 and tumor necrosis factor. The same phenomenon is not seen in patients without rheumatoid arthritis.

It’s less widely known, though, that these changes also contribute to the abnormal body composition found in rheumatoid arthritis patients. Understanding this interaction is important, Buttgereit and Burmester wrote, because glucocorticoid treatment is known to facilitate fat accumulation and redistribution between the body’s trunk and limbs.

“Disease exacerbations, decreased physical activity and disuse of muscles can further reduce lean mass, leading to decreased functional capacity and serious consequences for morbidity and mortality,” Buttgereit and Burmester wrote.

Rheumatoid arthritis patients often experience rheumatoid cachexia - the replacement of lean body mass with fat mass. This condition can raise the risk for comorbidities, including diabetes and cardiovascular disease.

According to Buttgereit and Burmester, the data from Konijn’s study is particularly important because it fills in the knowledge gap, affirming there are no major changes in relative body composition that occur with some forms of glucocorticoid treatments. The researchers obtained their results by recording total body mass and using dual energy X-ray absorptiometry, a straight-forward, fast, non-invasive technique for gathering body composition measurements. They measured total fat mass, total lean mass, and trunk:peripheral fat ratio at baseline and after 26 weeks of glucocorticoid treatment.

Overall, Buttgereit and Burmester said, Konijn’s study has two major results. First, in early on-set rheumatoid arthritis patients who had never received glucocorticoid or disease modifying anti-rheumatic drug therapies, total body mass increased by 1.6 kg after 26 weeks of treatment. 

The body mass index of glucocorticoid treated patients rose from 25.6 kg to 26.2 kg. That increase makes the presence of overweight and obesity at 26 weeks higher than at baseline. In fact, the 20 patients who were treated with higher cumulative glucocorticoid dose presented a 2.1 kg weight gain – more than the 1.1 kg seen in the 18 patients who received lower cumulative glucocorticoid doses. The 20 patients received a total of 2,275 mg via a combination-therapy regimen called COBRA, and their average daily dose was 12.5 mg. The 18 patients received, 1,750 mg via the same COBRA regimen, and their daily average dose was 9.6 mg.  

Based on the second major result, glucocorticoid-treated patients maintained their trunk:  peripheral fat ratio and proportional distribution of total body mass and fat mass. In essence, researchers observed no fat redistribution from the body’s limbs to the trunk within the study’s timeframe. The study also didn’t point to a dose-dependent effect of COBRA versus COBRA-light body composition treatment.

These observations were surprising, however, Buttgereit and Burmester said, because it’s known that glucocorticoid treatments alter energy metabolism, induce muscle wasting and fat accumulation, and redistribute fat from body’s limbs to its trunk.

But, Buttgereit and Burmester said, Konijn’s study isn’t without its limitations. Not only was the study short at 26 weeks, but it also included a small number of patients with no control group. In addition, the difference in cumulative glucocorticoid doses between the two groups - only 525 mg after 26 weeks - could be too small to cause a dose-dependent effect.

Researchers also didn’t record any data from the time period prior to rheumatoid arthritis onset, so they can’t determine if the observed total body mass and body mass index changes truly represent a real increase or whether they can be credited to the recovery of body mass previously lost to disease and, then, regained through successful glucocorticoid treatment.

Ultimately, Buttgereit and Burmester wrote, further research should investigate the long-term effects of glucocorticoid treatment in rheumatoid arthritis and other rheumatic diseases. It should also look at how disease processes influence body composition, as well as address whether cytokine-targeting biologic drugs influence body composition.

References:

Nicole P. C. Konijn, Lilian H. D. van Tuy, et al. "The short-term effects of two high-dose, step-down prednisolone regimens on body composition in early rheumatoid arthritis," Rheumatology. May 31, 2016. DOI: 10.1093/rheumatology/kew221

Frank Buttgereit, Gerd R. Burmester. "Rheumatoid arthritis: Glucocorticoid therapy and body composition," Nature Reviews Rheumatology. July 7, 2016. DOI: 10.1038/nrrheum.2016.114