Introduction: Oral bisphosphonates are widely-prescribed medications used to increase bone density in postmenopausal women with osteopenia or osteoporosis. Bisphosphonates prevent the attachment of osteoclasts to bone, and have been shown to have numerous anticancer properties. Several studies, including the Women's Health Initiative (WHI), have found that use of oral bisphosphonates is associated with reduced risk of developing breast cancer, but less is known about potential associations with other hormonal malignancies such as colorectal cancer (CRC). A few case-control and retrospective cohort studies have reported decreased risk of CRC among oral bisphosphonate users. In contrast, a large prospective cohort study found no association.

Methods: We evaluated the association between oral bisphosphonate use and CRC incidence in postmenopausal women, between 50 and 79 years of age, who participated in the WHI clinical trials and observational study. At baseline, all women completed an in-person interview covering demographic and general health information, and personal and family medical history. Oral bisphosphonate use was ascertained from an interviewer-administered inventory of regularly-used medications and supplements taken at baseline and over follow-up. Women who reported a personal history of CRC, ulcerative colitis, or colectomy at baseline were excluded from our analyses. Relative risks (RRs) were estimated by hazard ratios with 95% confidence intervals (CI) using Cox proportional hazards regression. Estimates were adjusted for WHI study component, hormone randomization assignment, age, a composite 5-year fracture probability, colorectal endoscopy, mammography, body mass index, race, education, family history of CRC, smoking status, alcohol consumption, physical activity, estrogen-only use, estrogen-progestin use, nonsteroidal anti-inflammatory drug use, aspirin use, total calcium intake, and total vitamin D intake.

Results: Among 156,826 eligible women at baseline, 1,931 were diagnosed with incident invasive CRC during a median follow-up of 11.9 years. The prevalence of oral bisphosphonate use increased over study follow-up from about 2% at baseline to about 10% six years after baseline. Comparing oral bisphosphonate users at baseline to non-users at baseline, we observed no association with CRC risk (RR, 0.80; CI, 0.55-1.17, P = 0.24). Updating baseline use in regression models that treated oral bisphosphonate use as a time-varying covariate resulted in more precise estimates, but the RR did not achieve statistical significance at the 0.05 level (RR, 0.88; CI, 0.72-1.07, P = 0.20). These results were not substantially different by tumor site or stage at diagnosis.

Conclusions: Use of oral bisphosphonates was not associated with the risk of developing CRC in the postmenopausal women who participated in WHI.

Citation Format: Michael N. Passarelli, Polly A. Newcomb, Andrea Z. LaCroix, Dorothy S. Lane, Gloria Y.F. Ho, Rowan T. Chlebowski. Oral bisphosphonate use and colorectal cancer incidence in the Women's Health Initiative. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr A92.