October 15, 2009
TUCSON, Ariz. – Fayez K. Ghishan, MD, director of the Steele Children’s Research Center at the University of Arizona College of Medicine, has received a $605,250, two-year National Institutes of Health American Recovery and Reinvestment grant to study the role calcium plays in inflammatory bowel disease-related bone loss.
The grant, “Development of Intestinal Transport of Calcium and Phosphate,” is funded by the National Institute of Diabetes and Digestive and Kidney Diseases, part of NIH. It will expand the ongoing research conducted by Dr. Ghishan and his research team to include another key component related to bone health – calcium – and how inflammation affects calcium absorption by the gut and the kidneys.
“Our previous research focused on phosphate balance. This study will focus on calcium absorption, because it takes both to develop strong bones,” says Dr. Ghishan, also professor and head of the UA Department of Pediatrics. “It will enable us to better understand the mechanisms governing calcium absorption at systemic, cellular and molecular levels.”
In children and young adults suffering from inflammatory bowel diseases, like Crohn’s disease and ulcerative colitis, bone density frequently is affected, resulting in osteopenia or osteoporosis (decreased bone mineral density). Decreased bone mineral density results in a higher risk of bone fractures later in life.
“Although we have long suspected that calcium deficiency may be one of the underlying factors in IBD-related bone loss, the mechanisms by which the calcium absorptive and re-absorptive mechanisms are disrupted by chronic intestinal inflammation are largely unknown,” says Pawel Kiela, DVM, PhD, UA research associate professor and co-investigator of the study. “So it is vital to understand how inflammation affects the key players involved in the maintenance of calcium balance.”
One mechanism the research team will explore is the role the “Klotho” gene plays in how calcium is transported and absorbed by the kidneys. (The gene was named after one of the Fates, a Greek goddess that spins the thread of life, thus determining the lifespan of humans.) Previous research has established that Klotho is integral in the aging process, showing that when Klotho is down-regulated, signs of premature aging appear, including osteoporosis. More recently, the Steele Center has demonstrated that Klotho is down-regulated in acute and chronic colitis.
“This is a fascinating connection,” Dr. Kiela says. “We are now hypothesizing that when Klotho is down-regulated, it negatively affects renal calcium reabsorption, which along with other metabolic complications, contributes to colitis-associated calcium imbalance, and the resulting bone loss.”
“The more we understand the mechanisms involved in calcium and phosphate absorption, the better chance we will have of developing novel therapies to treat children and adults suffering from IBD-related bone loss,” Dr. Ghishan says.
The University of Arizona, University Physicians Healthcare and University Medical Center work together to care for patients, educate medical students, train resident-physicians and conduct clinical and basic research. The UA Steele Children’s Research Center and UMC are working together to build Diamond Children’s Medical Center (www.diamondchildrens.org), now under construction and scheduled to open in 2010. Diamond Children's will be Arizona’s only pediatric inpatient medical center connected to an academic research facility – the Steele Center (www.steelecenter.arizona.edu).