Bisphosphonate use and gastrointestinal tract cancer risk: Meta-analysis of observational studies

Table 3 Case-control studies (n = 3) included in meta-analysis regarding use of bisphosphonates and risk of cancer

Ref.	Country (study type)	Case selection method	Control sampling method	Medication data collection method (period)	Age, yr (mean±SD)	Sex ratio of cases (reference group)	Site of cancer	Type of drug (reference group)	Odd’s ratio (95% CI)	Adjustment	No. of cases/no. of controls
											Exposed	Unexposed
Green et al[8]	United Kingdom (nested case-control)	Review of computerized information (within participants of GPRD between 1995 -2005)	Matched on age (within 2 yr), sex, observation period in the database and general practice attended)	Review of computerized medical records (from 1995 until cancer diagnosis)	72 ± 11	M: 57; F: 43	Gastrointestinal cancer (esophageal, gastric, colorectal)	Any bisphosphonate use (no bisphosphonate use)	Esophageal cancer 1.30 (1.02-1.66); Gastric cancer 0.87 (0.64-1.19); colorectal cancer 0.87 (0.77-1.00)	Age, sex, observation period, general practice, BMI, cigarette smoking, alcohol intake	Esophageal cancer 90/345; gastric cancer 49/270; colorectal cancer 276/1555	Esophageal cancer 2864/14 376; gastric cancer 1969/9737; colorectal cancer 10 365/51 467
Nguyen et al[12]	United States (nested case-control)	Review of computerized information (within patients with Barrett’s esophagus in the national veterans affair database between 2000-2002)	Matched on age(interval of 5 yr) and Barrett’s esophagus index date	Review of computerized medical records (from Barrett’s esophagus diagnosis until 3 mo before cancer diagnosis)	65.0 ± 10.3	M: 2.6; F: 97.4	Esophageal cancer	Any bisphosphonate use, mostly alendronate (no bisphosphonate use)	0.81 (0.18-3.72)	Age, Barrett’s esophagus index date, race, non cancer disease comorbidity index, NSAID use, PPI use	2/13	114/683
Rennert et al[13]	Israel (conventional case-control)	Review of a computerized information (within postmenopausal women in CHS database between 2000-2006)	Matched on age, sex, residence, and ethnic group in CHS database	Review of CHS pharmacy records	71.1 ± NA	F: 100	Colorectal cancer	Any bisphosphonate use more than 1 yr (no bisphosphonate use)	0.41 (0.25-0.67)	BMI, family history of colorectal cancer, vegetable consumption, sports participation, use of low-dose aspirin, statins, vitamin D, postmenopausal hormones	53/100	880/833

E: Enrollment; F/U: Follow up; CI: Confidence interval; M: Male; F: Female; NA: Not available; BMI: Body mass index; NSAID: Nonsteroidal antiinflammatory drugs; PPI: Proton pump inhibitors; CHS: Clalit Health Service; GPRD: General Practice Research Database.