Current issues of ACP Journal Club are published in Annals of Internal Medicine


Therapeutics

Calcium supplements reduced recurrence of colorectal adenomas

ACP J Club. 1999 Sept-Oct;131:39. doi:10.7326/ACPJC-1999-131-2-039


Source Citation

Baron JA, Beach M, Mandel JS, et al., for the Calcium Polyp Prevention Study Group. Calcium supplements for the prevention of colorectal adenomas. N Engl J Med. 1999 Jan 14;340:101-7.


Abstract

Question

In patients who have had colorectal adenomas, is calcium supplementation effective for reducing recurrent adenomas?

Design

Randomized, double-blind, placebo-controlled trial with 45-month follow-up after randomization.

Setting

6 clinical centers and associated practices in the United States (Cleveland, Ohio; Lebanon, New Hampshire; Los Angeles, California; Iowa City, Iowa; Minneapolis, Minnesota; and Chapel Hill, North Carolina).

Patients

930 patients who were < 80 years of age (mean age 61 y, 72% men); were in good health; and had ≥ 1 histologically confirmed, large-bowel adenomas removed within 3 months before trial entry. Exclusion criteria were history of familial polyposis, invasive large-bowel cancer, malabsorption syndromes, or any condition that might be exacerbated by calcium supplements. Follow-up was 89%.

Intervention

After a 3-month placebo run-in period, patients were allocated to calcium carbonate, 3 g (1200 mg elemental calcium) (n = 464), or placebo (n = 466) given in 1 tablet twice daily for up to 4 years.

Main outcome measures

Incidence of adenoma after randomization, including those detected by using surveillance colonoscopy at 9 and 45 months after study medication was started.

Main results

At 45 months, fewer patients in the calcium group than in the placebo group had recurrence of ≥ 1 adenomas (P = 0.05) (Table); after adjustment for age, sex, number of previous adenomas, clinical center, and length of follow-up, the treatment effect remained (relative risk reduction 19%, 95% CI 1% to 33%). Fewer adenomas occurred in the calcium group than in the placebo group (mean number of adenomas 0.55 vs 0.73, P = 0.03). At 9 months, fewer patients in the calcium group had ≥ 1 adenomas (P = 0.02) (Table); fewer adenomas occurred in the calcium group than in the placebo group (mean number of adenomas 0.43 vs 0.60, P = 0.03).

Conclusion

In patients who have had colorectal adenomas, calcium supplementation reduced recurrent adenomas.

Sources of funding: In part, National Institutes of Health. Calcium and placebo tablets provided by Lederle (now Whitehall-Robins).

For correspondence: Dr. J.A. Baron, 7927 Rubin Building, Dartmouth-Hitchcock Medical Center, 1 Medical Center Drive, Lebanon, NH 03756, USA. FAX 603-650-5225.


Table. Calcium vs placebo for preventing recurrence of colorectal adenomas*

Outcomes Calcium Placebo RRR (95% CI) NNT (CI)
Recurrence at > 9 to 45 mo 31% 38% 17% (0 to 32) 16 (8 to 1283)
Recurrence at 0 to 9 mo 25% 33% 23% (4 to 38) 14 (8 to 79)

*Abbreviations defined in Glossary; RRR, NNT, and CI calculated from data in article.


Commentary

Calcium supplementation may prevent recurrent adenomas by binding bile acids that cause carcinogenic changes in animal colonic mucosa. Previous trials have produced conflicting results about the efficacy of calcium in the prevention of colorectal adenomas. This trial by Baron and colleagues is one of the largest, longest, and best-designed evaluations of the efficacy of calcium supplementation prophylaxis.

Calcium supplementation seems to have a small, but statistically significant, effect for prevention of recurrent adenomas. Several confounding factors, including age and length of follow-up, were controlled for when the adjusted risk ratio was being calculated. However, the type of adenomas in this trial must be considered; almost all recurrent adenomas were diminutive (1 to 9 mm in diameter), and few diminutive adenomas progress to colon cancer.

Characteristics of advanced adenomas may include villous histology, size > 10 mm in diameter, and high-grade dysplasia. These are the polyps that frequently progress to cancer. Unfortunately, this trial was not designed to identify a reduction in colon cancer or advanced polyps, and no difference in frequency of colon cancer or advanced adenomas was seen between the calcium supplementation and placebo groups.

On the basis of these data, calcium supplementation cannot be routinely prescribed to prevent recurrent adenomas. If future research shows that calcium supplementation prevents colon cancer or advanced polyps, then this recommendation will change. Nevertheless, calcium supplementation is inexpensive, safe, and may benefit other dis-orders (e.g., osteoporosis). Therefore, physicians may choose to individualize their care and consider offering calcium supplementation to selected patients, such as those with multiple recurrent adenomas on repeated surveillance colonoscopies.

Philip Schoenfeld, MD, MSEd, MSc
National Naval Medical CenterBethesda, Maryland, USA