TNF blockers improve bones in pediatric Crohn's disease

Last Updated: 2015-05-07

By Anne Harding

NEW YORK (Reuters Health) - Children with Crohn's disease (CD) who receive anti-tumor necrosis factor (TNF)-alpha inhibitors show improvements in bone density and structure, researchers say.

"The anti-TNF-alpha biologics have the potential to restore bone structure in children and adolescents," Dr. Lindsay M. Griffin, of New York University School of Medicine, told Reuters Health in a telephone interview. "The window of opportunity closes once growth and maturation are complete."

Anti-TNF-alpha inhibitors are increasingly being used as first-line treatment in pediatric inflammatory bowel disease, Dr. Griffin added, and "our findings here could lead to even earlier use of biologics."

Children with CD have low-density bones, thin cortical bone, and substantial muscle deficits, Dr. Griffin explained. Given that TNF-alpha has adverse effects on bone metabolism, she and her colleagues hoped deficits in trabecular bone mineral density (BMD) and cortical area would show improvements with anti-TNF-alpha treatment.

The researchers studied 74 children, ages five to 21, who were starting infliximab for CD at Children's Hospital of Philadelphia. Tibia peripheral quantitative computed tomography (pQCT) scans were done at baseline and 12 months after treatment began. More than 650 healthy children participating in a larger study of bone health served as a reference group.

At the outset, CD patients had lower height, trabecular BMD, cortical area, and muscle area Z-scores compared to the reference group. By 12 months, the Crohn's participants had shown significant improvements in height, trabecular BMD, cortical area, and muscle area Z-scores. Younger children had greater increases in trabecular BMD Z-scores, greater linear growth, and greater cortical area recovery than older children (p<0.001 both).

The researchers found, for instance, that median change in height for Crohn's participants came to 4.9 cm. Still, height scores remained lower at 12 months than in reference participants. Also, trabecular BMD scores increased over 12 months, but significant deficits remained.

Bone-specific alkaline phosphatase level increased a median of 75% during induction and was associated with 12-month improvements in trabecular BMD and cortical area scores (p<0.001 both).

At enrollment, 50% of participants had severe disease. That dropped to 6% at 10 weeks and 7% at 12 months.

At study end, 67 (91%) participants remained on TNF alpha inhibitors: 62 on infliximab, four on adalimumab, and one on certolizumab.

"We definitely need more long-term data to say are these changes over a year sustainable, do kids continue to get better, and ultimately does putting children on these anti-TNF biologics lead to a lower fracture rate," Dr. Griffin said.

Young CD patients given other treatments to improve bone health have not shown this type of recovery, she added. This suggests, according to Dr. Griffin, that the effect of infliximab could be due not just to the fact that children are growing again and eating better, but it could also be specifically related to its anti-TNF action.

The National Institutes of Health and the Penn Joint Center for Inflammatory Bowel Diseases supported this research.

SOURCE: http://bit.ly/1dtlq3N

J Clin Endocrinol Metab 2015.