Long-term oral bisphosphonates may double esophageal cancer risk

People who take oral bisphosphonates for bone disease over five years may be doubling their risk of developing esophageal cancer, according to a new study.

Researchers from the University of Oxford's Cancer Epidemiology Unit and the Medicines and Healthcare Products Regulatory Agency analyzed data from the UK General Practice Research Database, which has patient records for six million people registered with a National Health Service general practitioner. They reported results online in BMJ.

Researchers reviewed data on men and women more than 40 years old, uncovering 2,954 with esophageal cancer, 2,018 with stomach cancer and 10,641 with colorectal cancer diagnosed between 1995 and 2005. Each case was compared with five controls matched for age, sex, general practice and observation period.

Esophageal cancer increased in people with one or more previous prescriptions for oral bisphosphonates compared with those with no such prescriptions (relative risk [RR], 1.30; 95% CI, 1.02 to 1.66; P=0.02). Risk nearly doubled for people with 10 or more prescriptions than for those with one to nine prescriptions (RR, 1.93; 95% CI, 1.37 to 2.70). Risk more than doubled for those who used bisphosphonates for more than three years (average five) compared to no prescription (RR, 2.24; 95% CI, 1.47 to 3.43).

Stomach and colorectal cancers were not associated with prescription of bisphosphonate compared with no prescription (RR, 0.87; 95% CI, 0.64 to 1.19 and RR, 0.87; 95% CI, 0.77 to 1.00, respectively).

Risk did not differ significantly by bisphosphonate type, and risk in those with 10 or more bisphosphonate prescriptions did not vary by age, sex, smoking, alcohol intake, or body mass index; by diagnosis of osteoporosis, fracture, or upper gastrointestinal disease; or by prescription of acid suppressants, nonsteroidal anti-inflammatory drugs, or corticosteroids.

Typically, esophageal cancer develops in one per 1,000 people (0.5 per 1,000 in women and 1.5 per 1,000 in men) at age 60 to 79 over five years. According to incidence data published by the World Health Organization, researchers estimate that with five years' use of oral bisphosphonates, this would double to two cases (in women one case and in men three cases per 1,000).

An editorial from an FDA epidemiologist said, "The possibility of adverse effects on the oesophagus should prompt doctors who prescribe these drugs to consider risks versus benefits." It also suggests doctors "tell patients to report difficulty in swallowing and throat, chest, or digestive discomfort so that they can be promptly evaluated and possibly advised to discontinue the drug."