Fran Lowry
January 17, 2014

Full Story (may require free registration): http://www.medscape.com/viewarticle/819382

Chronic damage in the small intestine is a risk factor for hip fracture in patients with celiac disease (CD), according to a cohort study published online January 16 in the Journal of Clinical Endocrinology & Metabolism.

“[CD] is associated with an increased fracture risk, an increase that persists after diagnosis,” write Benjamin Lebwohl, MD, from Columbia University College of Physicians and Surgeons, New York City, and colleagues. “A significant proportion of patients with CD have persistent villous atrophy…on follow-up biopsy.”

One factor that has not been taken into account regarding the long-term fracture risk in CD has been variable rates of mucosal healing, the authors note. Duodenal villous atrophy, which is a characteristic histological finding in CD, recedes after patients begin a gluten-free diet.

However, studies have reached contradictory conclusions about whether fracture risk remains elevated long after the disease is diagnosed and managed with a gluten-free diet….

The researchers aimed to determine whether persistent villous atrophy, compared with mucosal healing, is associated with an increased risk for fracture, including type of fracture, among patients with CD undergoing a follow-up biopsy.

The researchers analyzed tissue samples from 7146 patients in Sweden who were diagnosed with celiac disease from July 1969 to February 2008 and who had undergone follow-up biopsies between 6 months and 5 years after their diagnoses.

The median age at diagnosis was 23 years (range, 2 – 49 years), and the median age of follow-up biopsy was 25 years (range, 5 – 51).

Forty-six percent of the patients were younger than 20 years at the time of their follow-up biopsy, 64% were female, and 45% had their follow-up biopsy between 1 and 2 years after their diagnosis. The patients were followed-up for a median of 10.3 years (range, 6.8 – 15.7 years) after being diagnosed and a median of 8.6 years (range, 5.2 – 13.8 years) after biopsy.

The researchers examined intestinal tissue from the biopsies to determine the level of damage. Of this study population, 3105 patients (43%) had persistent villous atrophy in which the intestinal tissue did not heal.

During the follow-up period, a fracture occurred in 975 patients (14%). The overall incidence of any fracture in this population was 1376 per 100,000 person-years of observation.

The risk for overall fracture in patients with persistent villous atrophy did not differ from the risk in those with mucosal recovery (adjusted hazard ratio [HR], 0.93; 95% confidence interval [CI], 0.82 – 1.06).

However, with regard to osteoporotic fractures, patients with persistent villous atrophy had a higher, although nonsignificant, risk (HR, 1.11; 95% CI, 0.84 – 1.46). The chance of fracture was greatest for fractures of the distal forearm (HR, 1.19; 95% CI, 0.84 – 1.69).

The authors point out that the number of events (n = 142) was small and that the increased risk for an osteoporotic fracture was significant during the first year after the follow-up biopsy (HR, 2.54; 95% CI, 1.15 – 5.61). Hip fractures, however, were more likely to occur in patients who had persistent tissue damage.

There were 89 hip fractures during the observation period, corresponding to a rate of 114 per 100,000 person-years of observation. The rate was 158 per 100,000 person-years of observation in patients with persistent villous atrophy compared with 69 per 100,000 person-years of observation in patients with mucosal healing.

Persistent villous atrophy also was associated with an increased risk for subsequent hip fracture (HR, 1.67; 95% CI, 1.05 – 2.66), which translated into an absolute excess risk of 63 events per 100,000 person-years.

Patients with persistent villous damage in turn had a heightened risk for hip fracture beginning 5 years after the follow-up biopsy (HR, 2.18; 95% CI, 1.17 – 4.05), indicating a higher long-term risk.

“Physicians have debated whether people with celiac disease actually benefit from a follow-up biopsy to determine the level of tissue healing taking place,” Dr. Lebwohl said in a news release. “These findings suggest that a follow-up biopsy can be useful for predicting complications down the road.”

The authors point out that their study has several limitations. For one, information about clinical symptoms, which may have prompted follow-up biopsy, were not available for all patients. In addition, patients undergoing a follow-up biopsy may have done so because of a new clinical development or worsening symptoms.

“Because our analysis was restricted to the first follow-up biopsy, long-term mucosal healing rates were not available, and these rates may affect fracture risk,” the authors add.

In addition, increased fracture rate in the persistent villous atrophy patients could be a result of an increased rate of severe trauma among this group, but details regarding trauma were not available in this database. Information about bone density, muscle mass, and fall risk was also unavailable.

The data also lacked information about potential confounders or mediators such as smoking, corticosteroid use, anthropometry, physical activity, and diabetes, all of which may affect the risk for fracture.

Follow-up histology may be useful to stratify patients with celiac disease with regard to their fracture risk, the authors conclude.

“Future studies should examine how persistent villous atrophy affects bone density, [subcutaneous] fat, fall risk, and predictors of fractures among patients attempting to adhere to the gluten-free diet,” they write.

The authors have disclosed no relevant financial relationships.

J Clin Endocrinol Metab. Published online January 16, 2014. Abstract