Table 2 Association between post-diagnostic bisphosphonate use and colorectal cancer-specific death

From: Post-diagnostic oral bisphosphonate use and colorectal cancer mortality: a population-based cohort study within the UK Clinical Practice Research Datalink

 

User

Non-user

      

Medication usage after diagnosis a

Cancer-specific mortality

All patients

Person years

Cancer-specific mortality

All patients

Person years

Unadjusted HR (95% CI), ( n =4792)

P -value

Adjusted b

HR (95% CI), ( n =4792)

P -value

Fully Adjusted c

HR (95% CI), ( n =3466)

P- value

Bisphosphonate user vs non-user

60

346

1145

1516

4445

20 423

0.94 (0.73, 1.22)

0.65

1.00 (0.77, 1.31)

1

1.11 (0.80, 1.54)

0.54

1–12 prescriptions

37

145

563

1516

4445

20,423

0.98 (0.71, 1.36)

0.91

1.03 (0.74, 1.43)

0.89

1.07 (0.70, 1.64)

0.76

>12 prescriptions

23

201

582

—

—

—

0.88 (0.58, 1.34)

0.56

0.96 (0.63, 1.47)

0.86

1.16 (0.72, 1.88)

0.54

1 to 365 DDDs

37

144

536

1516

4445

20,423

1.04 (0.75, 1.44)

0.83

1.08 (0.77, 1.50)

0.66

1.12 (0.73, 1.71)

0.6

⩾365 DDDs

23

202

610

—

—

—

0.82 (0.54, 1.24)

0.35

0.92 (0.61, 1.41)

0.71

1.09 (0.67, 1.77)

0.74

Nitrogen-containing bisphosphonate user vs non-user

54

322

1019

1522

4469

20,549

0.98 (0.74, 1.28)

0.87

1.09 (0.82, 1.44)

0.56

1.13 (0.80, 1.61)

0.48

Alendronate user vs non-user

44

273

837

1532

4518

20,731

1.02 (0.76, 1.38)

0.9

1.15 (0.84, 1.56)

0.38

1.25 (0.85, 1.84)

0.27

Subgroup analysis

Colon cancer

36

222

761

828

2542

11,758

0.92 (0.66, 1.29)

0.64

1.05 (0.74,1.49)

0.79

1.10 (0.72, 1.69)

0.7

Rectal cancer (including rectosigmoid junction)

24

124

384

688

1903

8665

1.02 (0.68, 1.53)

0.94

0.96 (0.63, 1.45)

0.83

1.18 (0.70, 1.98)

0.53

Female ⩾60 years old

42

246

854

477

1,413

6622

0.94 (0.68, 1.29)

0.7

1.05 (0.75, 1.46)

0.79

1.14 (0.75, 1.74)

0.53

Stages 1 and 2

23

180

630

321

1796

10,038

1.29 (0.84, 1.97)

0.24

1.42 (0.91, 2.21)

0.12

1.36 (0.86, 2.14)

0.19

Stages 3 and 4

19

82

233

727

1539

5800

0.88 (0.56, 1.39)

0.58

0.92 (0.58, 1.48)

0.73

0.92 (0.56, ,1.49)

0.73

Pre-diagnostic non-usersd

27

234

729

1370

4077

18,713

0.80 (0.55, 1.18)

0.26

0.82 (0.56,1.21)

0.32

0.84 (0.51, 1.39)

0.5

Sensitivity analysis

Increasing lag to 1 year

49

312

1012

1527

4479

20,556

0.92 (0.69, 1.22)

0.55

0.97 (0.72, 1.31)

0.86

1.12 (0.78, 1.59)

0.54

Propensity score matched analysise

32

113

565

37

113

577

—

—

0.88 (0.54, 1.42)

0.6

1.13 (0.62, 2.07)

0.68

User vs non-user 1 year before diagnosisf

35

109

540

1397

4311

23,752

1.04 (0. 75, 1.50)

0.81

1.08 (0.77, 1.52)

0.65

1.35 (0.90, 2.02)

0.14

  1. aMedication use modelled as a time varying covariate with an individual considered a non-user before 6 months after first medication usage (or 12th prescription) and user after this time, excluding deaths in the year after cancer diagnosis.
  2. bAdjusted for year of diagnosis, age at diagnosis, sex , site (colon/rectum for colorectal cancer) , surgery within 6 months, chemotherapy within 6 months, radiotherapy within 6 months, pre-diagnostic comorbidities (including myocardial infarction, cerebrovascular disease, congestive heart disease, chronic pulmonary disease, peripheral vascular disease, peptic ulcer disease, diabetes, renal disease and rheumatoid arthritis) pre-diagnostic smoking (missing category included), low-dose aspirin use, statin use, ACE inhibitor use, β-blocker use and NSAID use (all in the exposure period).
  3. cCohort restricted to those with available stage and grade information and analysis additionally adjusted for stage and grade.
  4. dAnalysis restricted to non-users in the year before diagnosis, restricted to individuals with at least 1 year of records before colorectal cancer diagnosis.
  5. ePropensity score calculated using logistic regression with bisphosphonate use as the outcome and the following exposure variables: low-dose aspirin use, statin use, ACE inhibitor use, β-blocker use, NSAID use (in first year after diagnosis), age, year, gender, surgery, radiotherapy, chemotherapy, cancer site (colon or rectum), comorbidities (before diagnosis, including cerebrovascular disease, chronic pulmonary disease, congestive heart disease, diabetes, myocardial infarction, peptic ulcer disease, peripheral vascular disease and renal disease) and smoking before diagnosis. Fully adjusted estimate model also includes stage and grade.
  6. fOn the basis ofone or more prescription in the year before cancer diagnosis, restricted to individuals with at least 1 year of records before a cancer diagnosis, does not exclude deaths in the first year after diagnosis. Adjusted analysis includes all variables used in footnote a with the exception of other medication usage that are adjusted for in the year before diagnosis.
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