High-dose steroids do not always cause bone loss in children

Study of kidney condition challenges conventional view of steroid effects

Children who take steroid drugs for a kidney condition called nephrotic syndrome do not suffer bone loss, a common side effect of steroid treatments in adults. A new study sheds light on the steroid’s mixed effects: the drug frequently causes obesity, which seems to protect children against bone loss.

Childhood nephrotic syndrome, which affects 3 out of 100,000 children, is the most common chronic kidney disease in children. Although it does not impair kidney function, it weakens the body’s ability to remove water and salt from the blood, and causes swelling in the belly, legs, and around the eyes.

Left untreated, the syndrome may progress to life-threatening complications. Fortunately, most cases of childhood nephrotic syndrome are steroid-sensitive, meaning that a corticosteroid drug such as prednisone relieves the symptoms. Furthermore, nephrotic syndrome usually disappears by the later teen years, with no permanent kidney damage.

“Unlike other childhood diseases treated with steroid drugs, such as inflammatory bowel disease or juvenile rheumatoid arthritis, nephrotic syndrome resolves quickly when treated,” said pediatric nephrologist Mary B. Leonard, M.D., of The Children’s Hospital of Philadelphia, lead author of the study. “We specifically chose steroid-sensitive nephrotic syndrome because we are able to isolate the drug’s effects on bones, without having an underlying systemic disease simultaneously affecting the bones.”

The team led by Dr. Leonard compared 60 children and adolescents with steroid-sensitive nephrotic syndrome to 195 healthy children. Specialized X-ray measurements showed no signs of osteoporosis, a loss in bone mass, among the nephrotic syndrome patients. The study appeared in the August 26 New England Journal of Medicine.

The researchers made adjustments for body mass index, an important consideration, since 38 percent of the children in the nephrotic syndrome sample were obese (in contrast, only 16 percent of the control subjects were obese, a proportion consistent with the general pediatric population). The disproportionate obesity among children with nephrotic syndrome disappears after the patients discontinue steroid treatments.

“While steroids tend to make children shorter and heavier than healthy children, increased weight is associated with an increase in bone mass,” said co-author Babette Zemel, Ph.D., of the Nutrition Center at Children’s Hospital. Specifically, whole-body measurements of bone mineral content were higher in children with nephrotic syndrome than in healthy children.

A possible explanation for the increased bone mass, she added, is that the extra physical load imposed by higher weight may stimulate the bones to grow stronger. Obesity may also induce hormones to increase bone mass.

Bone health in childhood strongly influences bone health in later life–including the degree to which older adults are vulnerable to osteoporosis-related fractures. “This report may help reassure doctors and parents that using steroids to treat children with nephrotic syndrome does not raise their risk of osteoporosis,” said Dr. Leonard. “There is some evidence that obesity raises a child’s risk of fracture, but this may be due to the force of a heavy child falling on an outstretched arm–and not to a weakening of the bone.”

In other childhood diseases treated with steroids, such as inflammatory bowel disease and juvenile rheumatoid arthritis, researchers have found bone loss in children. The authors suggest those underlying diseases, which involve systemic, persistent inflammation, may damage bones in a way that nephrotic syndrome does not. Drs. Leonard and Zemel are continuing their pediatric bone studies with more refined computed tomography (CT) techniques that provide richer data than the two-dimensional images produced by X-ray studies.

Co-authors with Drs. Leonard and Zemel, also from Children’s Hospital, were Justine Shults, Ph.D.; Bethany J. Foster, M.D.; and Virginia A. Stallings, M.D. Harold I. Feldman, M.D., and all the co-authors were also from the University of Pennsylvania School of Medicine. Grants from the National Institute of Health supported the study.