A study recently published in the Journal of Clinical Endicronology & Metabolism shows a drug approved to treat Crohn’s disease, ulcerative colitis, and related conditions leads to “rapid improvements” in bone density and structure. The study, which was conducted by former and current Children’s Hospital researchers, could offer Crohn’s disease patients a treatment for the growth and bone issues associated with the condition.
The study was led by Mary B. Leonard, MD, MSCE, while its first author was Lindsay M. Griffin, MD. Both Drs. Leonard and Griffin — now at Stanford University and New York University, respectively — were previously at The Children’s Hospital of Philadelphia, where the bulk of the work was performed. Children’s Hospital’s Robert N. Baldassano, MD, and Babette S. Zemel, PhD, also contributed to the Journal of Clinical Endocrinology & Metabolism (JCEM) study.
A chronic bowel disease, Crohn’s disease (CD) is marked by inflammation of the gastrointestinal tract that can lead to narrowed and blocked intestines and ulcers. Though CD’s cause remains unknown, it may be brought on on by environmental, immunological, and genetic factors. According to the Crohn’s and Colitis Foundation of America, CD affects “as many as 700,000 Americans,” and is seen more often in adolescents aged 15 to 35 years.
In addition to its well-known, abdominal symptoms — such as cramping, diarrhea, and blood in the stool — CD is also associated with an impact on bone health and growth.
To wit, a 2014 review published in the World Journal of Gastroenterology notes “growth failure and impaired nutritional status are seen in [65 to 85 percent] of children and adolescents diagnosed with [Crohn’s disease], and [15 to 40 percent] of these patients continue to suffer from growth deficiency through the course of their disease.”
Examining Infliximab’s Effect on Bone
The current JCEM study investigated the effect the monoclonal antibody infliximab — which is sold under the name Remicade — had on bone density and structure in a cohort of 74 patients aged 5 to 21 years. The researchers evaluated the patients over a 12-month period (at first infusion, 10 weeks, six months, and 12 months), comparing the cohort’s results to data from 650 healthy reference patients who took part in a larger study of bone health.
Infliximab works by blocking tumor necrosis factor alpha (TNF-α), a cell signaling protein that per the JCEM paper, “has direct adverse effects on bone metabolism and plays a pivotal role in CD pathogenesis.”
While previous studies had shown that infliximab treatment had an effect on CD patients’ linear growth, the drug’s “impact on bone modeling has not been established,” the researchers write. They measured changes trabecular bone density and cortical area over the course of the 12-month infliximab treatment, hypothesizing it would improve both measures.
And indeed, Dr. Leonard and colleagues found that the patients’ height, BMI, trabecular bone density, and cortical area all improved, with the data showing “rapid improvements in disease activity.” In addition, the investigators found trabecular bone density improvements were greater in younger patients, which suggests that “childhood provides a window of opportunity for recovery of trabecular and endocortical deficits.”
“We believe this study is important because it is the first to show that blocking this inflammatory cytokine can reverse bone loss,” Dr. Leonard said. “Children can regain bone structure, as well as density.”
Though they caution that their study had limitations and that further research is needed, the researchers note “anti-TNF-α therapy during growth and development is associated with rapid improvements in trabecular [bone density] and cortical structure.”
To read more, see the Journal of Clinical Endocrinology & Metabolism. To learn more about inflammatory bowel disease care and research at The Children’s Hospital of Philadelphia, visit the Center for Pediatric Inflammatory Bowel Disease.