Persistent Mucosal Damage and Risk of Fracture in Celiac Disease

Context: Celiac disease (CD) is associated with an increased fracture risk, an increase that persists after diagnosis. A significant proportion of patients with CD have persistent villous atrophy (VA) on follow-up biopsy. Objective: The objective of the study was to determine whether persistent VA impacts long-term fracture risk. Design: This was a cohort study. Setting and Patients: We identified all patients in Sweden with histological evidence of CD who underwent a follow-up biopsy and compared patients with persistent VA with those with mucosal healing. Main Outcome Measures: The following were measured: 1) any fracture; 2) likely osteoporotic fracture (defined as fractures of the hip, distal forearm, thoracic and lumbar spine, or proximal humerus); and 3) hip fracture. Results: Of 7146 patients, VA was present on follow-up biopsy in 43%. There was no significant association between persistent VA and overall fractures [hazard ratio (HR) of persistent VA compared with those with healing 0.93, 95% confidence interval (CI) 0.82-1.06] or with likely osteoporotic fractures (HR 1.11, 95% CI 0.84-1.46). Persistent VA was associated with an increased risk of hip fracture (HR 1.67, 95% CI 1.05-2.66). Hip fracture risk increased, depending on the degree of VA (HR for partial VA compared with those with healing 1.70, 95% CI 0.82-3.49, HR for subtotal/total VA compared with those with healing 2.16, 95% CI 1.06-4.41). Conclusions: Persistent VA on follow-up biopsy is predictive of hip fracture risk. The association between persistent VA and hip fractures, but not fractures overall, implies that thinner sc tissue