CALCIUM AND COLORECTAL EPITHELIAL-CELL PROLIFERATION IN ULCERATIVE-COLITIS

In persons at higher risk for colon cancer (e.g., those with sporadic adenoma or ulcerative colitis), compared to those at lower risk, colon ic epithelial cell proliferation kinetics are altered, We have shown p reviously that calcium supplementation appears to normalize the distri bution of proliferating cells without affecting the proliferation rate in the colorectal mucosa of sporadic adenoma patients, In a pilot ran domized, double-blind, placebo-controlled, clinical trial conducted co ncurrently with our previously published sporadic adenoma trial, we te sted whether calcium supplementation can also modulate cell proliferat ion kinetics in patients with ulcerative colitis, Ulcerative colitis p atients (n = 31) were randomized to placebo or 2.0 g of supplemental c alcium daily, Colorectal epithelial cell proliferation was determined by immunohistochemical detection of proliferating cell nuclear antigen labeling of cells in ''non-prep'' rectal biopsies taken at randomizat ion and after 2 months treatment, All biopsies were scored by one revi ewer, Differences in mean follow-up minus baseline labeling index (LI; the proportion of colon crypt epithelial cells that were labeled) and in the empty set(h) (proportion of labeled cells that were in the upp er 40% of the crypts) were compared with analysis of covariance. Pill- taking adherence was 97%, Biopsy-scoring reliability was high (r = 0.8 9). The pooled baseline LI and empty set(h) were 6.3% and 5.6%, respec tively. The LI in the calcium group decreased by 0.3% (proportionately , 3%) more than in the placebo group (P = 0.91), Similarly, the empty set(h) in the calcium group decreased by 0.5% (proportionately,10%) mo re than in the placebo group (P = 0.85). This pilot study does not sug gest that 2.0 g of calcium as calcium carbonate daily can substantiall y normalize either the rate or distribution of proliferating cells ove r a 2-month period in the colon crypts of patients with ulcerative col itis; a more definitive answer to the question of whether calcium may be effective would require a study with a larger sample size and/or ot her study design modifications.