Table 1 The main characteristics of 34 included studies.

From: Bisphosphonates and risk of cancers: a systematic review and meta-analysis

Study [year]	Population location	Study design	Study period	Sample size	Number of cases	Mean age (years)^a	Sex, female (%)	Types of bisphosphonates	Duration of bisphosphonates	Types of cancers
Fortuny et al. ⁶³	USA	Case–control study	2001–2005	936	469	63.6 ± NA	100	NA	NA	Endometrial cancer
Newcomb et al.⁶¹	USA	Case–control study	2003–2006	5911	2936	54.5 ± 8.9	100	NA	3–12 months; 13–24 months; ≥25 months	Breast cancer
Rennert et al.⁶⁵	Northern Israel	Case–control study	2000–2010	4039	1832	64.7 ± NA	100	Alendronate: 86.7%	<1 year; 1–2 years; 2–3 years; 3–4 years; 4–5 years; >5 years	Breast cancer
Rennert et al.⁶⁴	Northern Israel	Case–control study	2000–2006	1866	933	71.6 ± NA	100	Alendronate: 94.7%	<1 year; 1–2 years; 2–3 years; >3 years	Colorectal cancer
Wright et al. ⁶⁰	UK	Case–control study	1995–2007	43,180	8636	64.7 ± NA	36.4	NA	NA	Oesophageal and gastric cancer
Rennert et al.⁶²	Israel	Case–control study	2003–2010	805	464	67.2 ± NA	100	Alendronate and risedronate	<1 year; 1–2 years; 2–3 years; 3–4 years; 4–5 years; >5 years	Endometrial and ovarian cancer
Green et al.⁵⁹	UK	Nested case–control study	NA	93,678	15,613	≥40	NA	NA	NA	Oesophageal, gastric and colorectal cancer
Nguyen et al.⁵⁶	USA	Nested case–control study	2000–2002	812	116	64.7 ± 10.3	2.6	Alendronate, risedronate, etidronate, tiludronate and ibandronate	≥1 prescription	Oesophageal cancer
Chen et al. ⁵⁰	Taiwan, China	Nested case–control study	2001–2008	3093	282	NA	NA	Alendronate	<1 year; ≥1 year	Oesophageal cancer
Singh et al. ⁵²	Canada	Nested case–control study	2000–2009	59,667	5425	≥50	46.0	Alendronate, risedronate, etidronate, pamidronate, clodronate and zoledronate	<210 days; 210–572 days; 573–1250 days; >1250 days	Colorectal cancer
Vinogradova et al.⁵³	UK	Nested case–control study	1997–2011	1,023,458	180,401	69.5 ± 10.0	49.7	Alendronate, risedronate, etidronate and ibandronate	<1 year; ≥1 year	Non-gastrointestinal cancers^b
Vinogradova et al.⁵⁴	UK	Nested case–control study	1997–2011	217,569	28,625	≥50	49.7	Alendronate, etidronate, ibandronate and risedronate	<1 year; ≥1 year	Oesophageal, gastric and colorectal cancer
Vogtmann et al.⁵⁵	California	Nested case–control study	1997–2011	146,567	2934	67.2 ± 12.1	30.8	NA	<1 year; ≥1 year	Oesophageal and gastric cancer
Jung et al. ¹²	Korea	Nested case–control study	2002–2013	8540	1708	≥40	66.6	Alendronate, risedronate, etidronate, ibandronate, clodronate and pamidronate	NA	Oesophageal and gastric cancer
Busby et al.⁵⁷	Scotland	Nested case–control study	1993–2011	18,035	3098	69.2 ± 11.2	35.4	NA	NA	Oesophageal and gastric cancer
Vogtmann et al.⁵⁸	California	Nested case–control study	1997–2011	612,039	12,505	65.9 ± 12.9	48.5	Alendronate, risedronate, etidronate, ibandronate and tiludronate	<1 year; ≥1 year	Colorectal cancer
Chung et al.⁵¹	Denmark	Nested case–control study	1996–2013	30,228	2748	NA	37.4	Alendronate, risedronate, etidronate, ibandronate, clodronate and zoledronate	≤3 months; 3–12 months; >12 months	Renal cell carcinoma
Chiang et al.⁶⁶	Taiwan, China	Case cohort study	1998–2009	27,603	3467	73.5 ± 8.4	100	Alendronate	≤2 years; >2 years	All types of cancer
Abrahamsen et al.⁴⁰	Denmark	Cohort study	1995–2005	41,034	85	74.3 ± 8.8	89.1	Alendronate, risedronate, etidronate, ibandronate and clodronate	Mean 2.1 years	Oesophageal and gastric cancer
Cardwell et al.³⁸	UK	Cohort study	1996–2006	83,652	314	70.0 ± 11.4	81.0	Alendronate, risedronate, etidronate, ibandronate, tiludronate and clodronate	NA	Oesophageal cancer
Chlebowski et al.⁴¹	USA	Cohort study	1993–2005	154,768	6276	50–79	100	Alendronate, etidronate, tiludronate and pamidronate	<1 year; 1–3 years; ≥3 years	Breast cancer
Vestergaard et al.¹¹	Denmark	Cohort study	1996–2006	414,245	103,562	70.5 ± 11.4	84.7	Alendronate, etidronate and clodronate	NA	Digestive system cancers^c
Vestergaard et al.⁴⁸	Denmark	Cohort study	1996–2006	348,426	884	71.1 ± 10.7	100	Alendronate, risedronate, etidronate, ibandronate, clodronate, pamidronate and zoledronate	NA	Breast cancer
Abrahamsen et al.³⁷	Denmark	Cohort study	1996–2005	153,030	318	71.9 ± 10.0	100	Alendronate	NA	Oesophageal and gastric cancer
Cardwell et al.¹³	UK	Cohort study	1996–2006	83,652	5956	70.0 ± 11.4	81.0	NA	< 1 year; 1–2 years; 2–3 years; 3–4 years	All types of cancer
Khalili et al.⁴⁵	USA	Cohort study	1998–2008	86,277	801	64.7 ± 7.1	100	Alendronate, risedronate, etidronate and other bisphosphonates	1–2 years; 3–4 years; ≥5 years	Colorectal cancer
Lee et al.³⁹	Taiwan, China	Cohort study	1998–2009	21,918	873	NA	84.4	Alendronate	NA	All types of cancer
Pazianas et al.⁴⁷	Denmark	Cohort study	1996–2005	153,030	1683	71.9 ± 10.0	100	Alendronate	NA	Colon cancer
Passarelli et al.¹⁴	USA	Cohort study	1993–2009	143,335	1931	63.2 ± 7.2	100	Alendronate, risedronate, etidronate and tiludronate	<1 year; 1–3 years; ≥3 years	Colorectal cancer
Alford et al.⁴⁶	USA	Cohort study	1993–2001	23,485	97	55–74	100	Alendronate, risedronate, etidronate and ibandronate	NA	Endometrial cancer
Newcomb et al.⁴³	USA	Cohort study	1993–2010	83,286	1123	63.0 ± 7.2	100	Alendronate, risedronate, etidronate and tiludronate	<1 year; 1–3 years; ≥3 years	Endometrial cancer
Fournier et al.⁴⁹	France	Cohort study	2004–2011	64,438	2407	62.8 ± 6.4	100	Alendronate, risedronate, etidronate, ibandronate, tiludronate and zoledronate	<0.5 year; 0.5–1 years; 1–3 years; ≥3 years	Breast cancer
Tao et al.⁴²	USA	Cohort study	1993–2013	151,134	2511	50–79	100	Alendronate, risedronate, etidronate, tiludronate, pamidronate and zoledronate	<0.67 years; 0.67–1.49 years; 1.50–2.99 years; ≥3 years	Lung cancer
Bae et al.⁴⁴	Korea	Cohort study	2003–2013	204,525	2183	57.2 ± NA	100	Alendronate and risedronate	NA	Female cancer^d

NA not available.
^aIf mean values of age were unavailable, median or range was extracted.
^bNon-gastrointestinal cancers: bladder, breast, cervical, endometrial, lung, melanoma, ovarian, pancreas and prostate cancer.
^cDigestive system cancers: oesophageal, liver, pancreas, colon and small intestinal cancer.
^dBreast, endometrial and ovarian cancer.

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Table 1 The main characteristics of 34 included studies.

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