Reduced colon cancer incidence and mortality in postmenopausal women treated with an oral bisphosphonate—Danish National Register Based Cohort Study

• Published in: Osteoporosis international Vol. 23; no. 11; pp. 2693 - 2701
• Main Authors: Pazianas, M., Abrahamsen, B., Eiken, P. A., Eastell, R., Russell, R. Graham G.
• Format: Journal Article
• Language: English
• Published: London Springer-Verlag 01-11-2012; Springer Nature B.V
• Subjects: Administration, Oral; Age; Aged; Aged, 80 and over; Alendronate - administration & dosage; Alendronate - therapeutic use; Alendronic acid; Bisphosphonates; Bone Density Conservation Agents - administration & dosage; Bone Density Conservation Agents - therapeutic use; Bone diseases; Colon cancer; Colorectal cancer; Colorectal Neoplasms - epidemiology; Colorectal Neoplasms - prevention & control; Denmark - epidemiology; Diphosphonates - administration & dosage; Diphosphonates - therapeutic use; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug therapy; Endocrinology; Female; Humans; Incidence; Intestine; Lung diseases; Medicine; Medicine & Public Health; Middle Aged; Mortality; Mouth; Original Article; Orthopedics; Osteoporosis; Osteoporosis, Postmenopausal - drug therapy; Osteoporosis, Postmenopausal - epidemiology; Post-menopause; Prevention; Registries; Rheumatology; Risk factors; Survival; Survival Analysis; Women; Denmark; Oral bisphosphonates; Mortality; Colorectal cancer; Incidence
• ISSN: 0937-941X; 1433-2965
• DOI: 10.1007/s00198-012-1902-4

Summary
In this Danish national register-based cohort study, we examined the effects of alendronate on the development of colon cancers and survival. The incidence of colon cancer and mortality rate, once colon cancer had been diagnosed, were lower in patients treated with alendronate, posing the question whether alendronate acts as chemopreventive.
Introduction
When bisphosphonates are given by mouth, around 99% remains non-absorbed in the intestine. Based on their biochemical actions, we predicted that oral bisphosphonates might prevent colon cancers.
Methods
This is a Danish national register-based cohort study. We identified 30,606 women aged 50+, mean age 71.9 years, who had not previously taken treatments for osteoporosis, who began to take alendronate in 1996–2005, and assigned 124,424 individually age- and gender-matched control subjects. The main outcome measure was colorectal cancers incidence and post-diagnosis survival in patients taking oral alendronate for osteoporosis.
Results
Cox proportional hazards analysis of death due to colon cancer showed lower risk in alendronate users, crude hazard ratio (HR) 0.69 (95% CI 0.59–0.81) with an adjusted HR of 0.62 (95% CI 0.52–0.72). The reduction in risk comprised both a lower incidence of colon cancer-adjusted HR 0.69 (95% CI 0.60–0.79) and a lower mortality once colon cancer had been diagnosed, adjusted HR 0.82 (95% CI 0.70–0.97). Weekly alendronate was associated with a greater risk reduction than daily alendronate. The main findings were unaffected by excluding patients from the analysis who had pulmonary disease, a major co-morbid condition in users of alendronate and an important cause of death.
Conclusions
The risk of overall deaths from cancer and in particular death caused by colon cancer was significantly and substantially decreased (40%) in patients treated with alendronate, with survival curves deviating progressively after 2 years. Also, the incidence of colon cancer was lower in those patients.