Scolaris Content Display Scolaris Content Display

Cochrane Database of Systematic Reviews

Bisphosphonates for advanced prostate cancer

Information

DOI:
https://doi.org/10.1002/14651858.CD006250.pub2Copy DOI
Database:
  1. Cochrane Database of Systematic Reviews
Version published:
  1. 26 December 2017see what's new
Type:
  1. Intervention
Stage:
  1. Review
Cochrane Editorial Group:
  1. Cochrane Urology Group

Copyright:
  1. Copyright © 2017 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

Article metrics

Altmetric:

Cited by:

Cited 0 times via Crossref Cited-by Linking

Collapse

Authors

  • Sascha Macherey

    Cochrane Haematological Malignancies Group, Department I of Internal Medicine, University Hospital of Cologne, Cologne, Germany

  • Ina Monsef

    Cochrane Haematological Malignancies Group, Department I of Internal Medicine, University Hospital of Cologne, Cologne, Germany

  • Franziska Jahn

    Department of Internal Medicine IV; Hematology/Oncology, Martin‐Luther‐University Halle‐Wittenberg, Halle, Germany

  • Karin Jordan

    Department of Medicine V, University of Heidelberg, Heidelberg, Germany

  • Kwok Keung Yuen

    Department of Clinical Oncology, Queen Mary Hospital, Hong Kong, China

  • Axel Heidenreich

    Department of Urology, University Hospital Cologne, Cologne, Germany

  • Nicole Skoetz

    Correspondence to: Cochrane Haematological Malignancies Group, Department I of Internal Medicine, University Hospital of Cologne, Cologne, Germany

    [email protected]

Contributions of authors

SM: data extraction and analysis, drafting of final review.

IM: developed and ran search strategies and provided databases.

FJ: clinical expertise.

KJ: clinical expertise.

KKY: clinical expertise for the first version of this review.

AH: clinical expertise.

NS: data extraction and analysis, content and methodologic input.

Sources of support

Internal sources

  • University Hospital of Cologne, Department I of Internal Medicine, Germany.

External sources

  • No sources of support supplied

Declarations of interest

SM: none known.

IM: none known.

FJ: received payment for lectures from MSD, Riemser and Tesaro; received travel, accommodation or meeting expenses from Pfizer, Roche, Tesaro.

KJ: received payment for lectures from Amgen.

KKY: none known.

AH: none known.

NS: none known.

Acknowledgements

The authors of the first version of this review would like to thank Mrs Bernadette Coles MSc for developing and running the search strategies for this review.

We thank the authors of the first published version of this review, Mike Shelley, Wai Man Sze, Timothy J Wilt and Malcolm D Mason.

We thank the Cochrane Urology Group for their support, including the editors for their feedback on this review. We also thank the referees for their appreciated feedback: Stefan Krause, Stefanie Schmidt and Gunhild von Amsberg.

Version history

Published

Title

Stage

Authors

Version

2017 Dec 26

Bisphosphonates for advanced prostate cancer

Review

Sascha Macherey, Ina Monsef, Franziska Jahn, Karin Jordan, Kwok Keung Yuen, Axel Heidenreich, Nicole Skoetz

https://doi.org/10.1002/14651858.CD006250.pub2

2006 Oct 18

Bisphosphonates for advanced prostate cancer

Review

Kwok Keung Yuen, Mike Shelley, Wai Man Sze, Timothy J. Wilt, Malcolm Mason

https://doi.org/10.1002/14651858.CD006250

Differences between protocol and review

We included all trials fitting the inclusion criteria, irrespective of outcomes reported. The protocol and first version of the review included only trials that evaluated pain. However, as this is not in line with the methodologic expectations of Cochrane intervention reviews (MECIR) guidelines, we included all trials irrespective of the outcomes reported.

For continuous outcomes we would have calculated mean differences, or in case different scales would have been used, standardized mean difference (SMD). For time‐to‐event outcomes, we would have extracted the hazard ratio (HR) from published data according to Parmar 1998 and Tierney 2007, but neither continuous outcomes nor time‐to‐event outcomes have been reported.

In contrast to the protocol and the prior version of this review, we did not include trials with active control groups (other bisphosphonates). We initially identified three trials comparing different doses and types of bisphosphonates, but these studies have been designed heterogeneously. As agreed with the Editorial Base, in the final analysis, we subsequently decided to omit analysis of these trials due to potentially imbalanced results with restricted applicability.

Notes

Some passages in this review, especially in the methods part, are from the standard template of the Cochrane Haematological Malignancies Review Group.

Keywords

MeSH

PICOs

Population
Intervention
Comparison
Outcome

The PICO model is widely used and taught in evidence-based health care as a strategy for formulating questions and search strategies and for characterizing clinical studies or meta-analyses. PICO stands for four different potential components of a clinical question: Patient, Population or Problem; Intervention; Comparison; Outcome.

See more on using PICO in the Cochrane Handbook.

Study flow diagram.
Figures and Tables -
Figure 1

Study flow diagram.

Risk of bias summary: review authors' judgments about each risk of bias item for each included study.
Figures and Tables -
Figure 2

Risk of bias summary: review authors' judgments about each risk of bias item for each included study.

Forest plot of comparison: 1 Bisphosphonates versus control, outcome: 1.1 Proportion of participants with pain response.
Figures and Tables -
Figure 3

Forest plot of comparison: 1 Bisphosphonates versus control, outcome: 1.1 Proportion of participants with pain response.

Forest plot of comparison: 1 Bisphosphonates versus control, outcome: 1.2 Skeletal‐related events: any.
Figures and Tables -
Figure 4

Forest plot of comparison: 1 Bisphosphonates versus control, outcome: 1.2 Skeletal‐related events: any.

Forest plot of comparison: 1 Bisphosphonates versus control, outcome: 1.9 Mortality.
Figures and Tables -
Figure 5

Forest plot of comparison: 1 Bisphosphonates versus control, outcome: 1.9 Mortality.

Forest plot of comparison: 1 Bisphosphonates versus control, outcome: 1.11 Adverse events: renal.
Figures and Tables -
Figure 6

Forest plot of comparison: 1 Bisphosphonates versus control, outcome: 1.11 Adverse events: renal.

Comparison 1 Bisphosphonates versus control, Outcome 1 Proportion of participants with pain response.
Figures and Tables -
Analysis 1.1

Comparison 1 Bisphosphonates versus control, Outcome 1 Proportion of participants with pain response.

Comparison 1 Bisphosphonates versus control, Outcome 2 Skeletal‐related events: any.
Figures and Tables -
Analysis 1.2

Comparison 1 Bisphosphonates versus control, Outcome 2 Skeletal‐related events: any.

Comparison 1 Bisphosphonates versus control, Outcome 3 Skeletal‐related events: pathologic fracture.
Figures and Tables -
Analysis 1.3

Comparison 1 Bisphosphonates versus control, Outcome 3 Skeletal‐related events: pathologic fracture.

Comparison 1 Bisphosphonates versus control, Outcome 4 Skeletal‐related events: pathologic fractures: vertebral fracture.
Figures and Tables -
Analysis 1.4

Comparison 1 Bisphosphonates versus control, Outcome 4 Skeletal‐related events: pathologic fractures: vertebral fracture.

Comparison 1 Bisphosphonates versus control, Outcome 5 Skeletal‐related events: pathologic fractures: non‐vertebral fracture.
Figures and Tables -
Analysis 1.5

Comparison 1 Bisphosphonates versus control, Outcome 5 Skeletal‐related events: pathologic fractures: non‐vertebral fracture.

Comparison 1 Bisphosphonates versus control, Outcome 6 Skeletal‐related events: spinal cord compression.
Figures and Tables -
Analysis 1.6

Comparison 1 Bisphosphonates versus control, Outcome 6 Skeletal‐related events: spinal cord compression.

Comparison 1 Bisphosphonates versus control, Outcome 7 Skeletal‐related events: bone radiation therapy.
Figures and Tables -
Analysis 1.7

Comparison 1 Bisphosphonates versus control, Outcome 7 Skeletal‐related events: bone radiation therapy.

Comparison 1 Bisphosphonates versus control, Outcome 8 Skeletal‐related events: bone surgery.
Figures and Tables -
Analysis 1.8

Comparison 1 Bisphosphonates versus control, Outcome 8 Skeletal‐related events: bone surgery.

Comparison 1 Bisphosphonates versus control, Outcome 9 Mortality.
Figures and Tables -
Analysis 1.9

Comparison 1 Bisphosphonates versus control, Outcome 9 Mortality.

Comparison 1 Bisphosphonates versus control, Outcome 10 Adverse events: nausea.
Figures and Tables -
Analysis 1.10

Comparison 1 Bisphosphonates versus control, Outcome 10 Adverse events: nausea.

Comparison 1 Bisphosphonates versus control, Outcome 11 Adverse events: renal.
Figures and Tables -
Analysis 1.11

Comparison 1 Bisphosphonates versus control, Outcome 11 Adverse events: renal.

Comparison 1 Bisphosphonates versus control, Outcome 12 Adverse events: bone pain.
Figures and Tables -
Analysis 1.12

Comparison 1 Bisphosphonates versus control, Outcome 12 Adverse events: bone pain.

Comparison 1 Bisphosphonates versus control, Outcome 13 Adverse events: osteonecrosis of the jaw.
Figures and Tables -
Analysis 1.13

Comparison 1 Bisphosphonates versus control, Outcome 13 Adverse events: osteonecrosis of the jaw.

Comparison 1 Bisphosphonates versus control, Outcome 14 Proportion of participants with decreased analgesic consumption.
Figures and Tables -
Analysis 1.14

Comparison 1 Bisphosphonates versus control, Outcome 14 Proportion of participants with decreased analgesic consumption.

Comparison 1 Bisphosphonates versus control, Outcome 15 Proportion of participants with disease progression.
Figures and Tables -
Analysis 1.15

Comparison 1 Bisphosphonates versus control, Outcome 15 Proportion of participants with disease progression.

Comparison 1 Bisphosphonates versus control, Outcome 16 Sensitivity analysis: pain response (low risk of bias vs high risk of bias).
Figures and Tables -
Analysis 1.16

Comparison 1 Bisphosphonates versus control, Outcome 16 Sensitivity analysis: pain response (low risk of bias vs high risk of bias).

Comparison 1 Bisphosphonates versus control, Outcome 17 Subgroup analysis: pain response (amino‐bisphosphonate vs non‐amino‐bisphosphonate).
Figures and Tables -
Analysis 1.17

Comparison 1 Bisphosphonates versus control, Outcome 17 Subgroup analysis: pain response (amino‐bisphosphonate vs non‐amino‐bisphosphonate).

Comparison 1 Bisphosphonates versus control, Outcome 18 Subgroup analysis: pain response (route of administration).
Figures and Tables -
Analysis 1.18

Comparison 1 Bisphosphonates versus control, Outcome 18 Subgroup analysis: pain response (route of administration).

Comparison 1 Bisphosphonates versus control, Outcome 19 Sensitivity analysis: skeletal‐related events (low risk of bias vs high risk of bias).
Figures and Tables -
Analysis 1.19

Comparison 1 Bisphosphonates versus control, Outcome 19 Sensitivity analysis: skeletal‐related events (low risk of bias vs high risk of bias).

Comparison 1 Bisphosphonates versus control, Outcome 20 Sensitivity analysis: skeletal‐related events (full‐text vs abstract publication).
Figures and Tables -
Analysis 1.20

Comparison 1 Bisphosphonates versus control, Outcome 20 Sensitivity analysis: skeletal‐related events (full‐text vs abstract publication).

Comparison 1 Bisphosphonates versus control, Outcome 21 Subgroup analysis: skeletal‐related events (amino‐bisphosphonate versus non‐amino‐bisphosphonate).
Figures and Tables -
Analysis 1.21

Comparison 1 Bisphosphonates versus control, Outcome 21 Subgroup analysis: skeletal‐related events (amino‐bisphosphonate versus non‐amino‐bisphosphonate).

Comparison 1 Bisphosphonates versus control, Outcome 22 Subgroup analysis: skeletal‐related events (route of administration).
Figures and Tables -
Analysis 1.22

Comparison 1 Bisphosphonates versus control, Outcome 22 Subgroup analysis: skeletal‐related events (route of administration).

Comparison 1 Bisphosphonates versus control, Outcome 23 Sensitivity analysis: mortality (low risk of bias vs high risk of bias)).
Figures and Tables -
Analysis 1.23

Comparison 1 Bisphosphonates versus control, Outcome 23 Sensitivity analysis: mortality (low risk of bias vs high risk of bias)).

Comparison 1 Bisphosphonates versus control, Outcome 24 Sensitivity analysis: mortality (full‐text vs abstract publication).
Figures and Tables -
Analysis 1.24

Comparison 1 Bisphosphonates versus control, Outcome 24 Sensitivity analysis: mortality (full‐text vs abstract publication).

Comparison 1 Bisphosphonates versus control, Outcome 25 Subgroup analysis: mortality (amino‐bisphosphonate vs non‐amino‐bisphosphonate).
Figures and Tables -
Analysis 1.25

Comparison 1 Bisphosphonates versus control, Outcome 25 Subgroup analysis: mortality (amino‐bisphosphonate vs non‐amino‐bisphosphonate).

Comparison 1 Bisphosphonates versus control, Outcome 26 Subgroup analysis: mortality (route of administration).
Figures and Tables -
Analysis 1.26

Comparison 1 Bisphosphonates versus control, Outcome 26 Subgroup analysis: mortality (route of administration).

Comparison 1 Bisphosphonates versus control, Outcome 27 Sensitivity analysis: adverse event: nausea (low risk of bias vs high risk of bias).
Figures and Tables -
Analysis 1.27

Comparison 1 Bisphosphonates versus control, Outcome 27 Sensitivity analysis: adverse event: nausea (low risk of bias vs high risk of bias).

Comparison 1 Bisphosphonates versus control, Outcome 28 Subgroup analysis: adverse event: nausea (amino‐bisphosphonate vs non‐amino‐bisphosphonate).
Figures and Tables -
Analysis 1.28

Comparison 1 Bisphosphonates versus control, Outcome 28 Subgroup analysis: adverse event: nausea (amino‐bisphosphonate vs non‐amino‐bisphosphonate).

Comparison 1 Bisphosphonates versus control, Outcome 29 Subgroup analysis: adverse event: nausea (route of administration).
Figures and Tables -
Analysis 1.29

Comparison 1 Bisphosphonates versus control, Outcome 29 Subgroup analysis: adverse event: nausea (route of administration).

Comparison 1 Bisphosphonates versus control, Outcome 30 Sensitivity analysis: renal (low risk of bias vs high risk of bias).
Figures and Tables -
Analysis 1.30

Comparison 1 Bisphosphonates versus control, Outcome 30 Sensitivity analysis: renal (low risk of bias vs high risk of bias).

Comparison 1 Bisphosphonates versus control, Outcome 31 Subgroup analysis: renal (amino‐bisphosphonate vs non‐amino‐bisphosphonate).
Figures and Tables -
Analysis 1.31

Comparison 1 Bisphosphonates versus control, Outcome 31 Subgroup analysis: renal (amino‐bisphosphonate vs non‐amino‐bisphosphonate).

Comparison 1 Bisphosphonates versus control, Outcome 32 Subgroup analysis: renal (route of administration).
Figures and Tables -
Analysis 1.32

Comparison 1 Bisphosphonates versus control, Outcome 32 Subgroup analysis: renal (route of administration).

Summary of findings for the main comparison. Bisphosphonates compared to placebo/no treatment for advanced prostate cancer

Bisphosphonates compared to control for advanced prostate cancer

Patient or population: men with advanced prostate cancer

Settings:

Intervention: bisphosphonate

Comparison: control

Outcomes

No of participants
(studies)
Follow‐up

Quality of the evidence
(GRADE)

Relative effect
(95% CI)

Anticipated absolute effects* (95% CI)

Risk with control

Risk difference with bisphosphonates

Proportion of participants with pain response

Follow‐up: 5‐12 months

876
(3 RCTs)

⊕⊕⊝⊝
Low1,2

RR 1.15
(0.93 to 1.43)

Study population

265 per 1000

40 more per 1000
(19 fewer to 114 more)

Skeletal‐related events: any, composite outcome
Follow‐up: 5‐60 months

3153
(9 RCTs)

⊕⊕⊕⊝
Moderate3

RR 0.87
(0.81 to 0.94)

Study population

448 per 1000

58 fewer per 1000
(85 fewer to 27 fewer)

Mortality
Follow‐up: 12‐60 months

2450
(9 RCTs)

⊕⊕⊕⊝
Moderate3

RR 0.97
(0.91 to 1.04)

Study population

517 per 1000

16 fewer per 1000
(47 fewer to 21 more)

Quality of life

Not estimable

Adverse events: nausea
Follow‐up: 5‐36 months

3008
(9 RCTs)

⊕⊕⊕⊝
Moderate3

RR 1.19
(1.00 to 1.41)

Study population

35 per 1000

7 more per 1000
(0 fewer to 14 more)

Adverse events: renal

Follow‐up: 5‐36 months

1794
(7 RCTs)

⊕⊕⊕⊝
Moderate3

RR 1.65
(1.11 to 2.46)

Study population

34 per 1000

22 more per 1000
(4 more to 50 more)

Adverse events: osteonecrosis of the jaw
Follow‐up: 5‐24 months

1626
(5 RCTs)

⊕⊝⊝⊝
Very low3,4

RR 1.92
(0.75 to 4.90)

Study population

7 per 1000

7 more per 1000
(2 fewer to 29 more)

Proportion of participants with disease progression
Follow‐up: 12‐60 months

2115
(7 RCTs)

⊕⊕⊕⊝
Moderate3

RR 0.95
(0.90 to 0.99)

Study population

710 per 1000

36 fewer per 1000
(71 fewer to 7 fewer)

*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).

CI: confidence interval; RCT: randomized controlled trial; RR: risk ratio.

GRADE Working Group grades of evidence
High quality: We are very confident that the true effect lies close to that of the estimate of the effect.
Moderate quality: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.
Low quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect.
Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect.

1Potential risk of performance, detection and attrition bias leading to downgrading (one point).

2Small number of events leading to downgrading (one point).

3Potential risk of performance and attrition bias leading to downgrading (one point).

4Very small number of events leading to downgrading (two points).

Figures and Tables -
Summary of findings for the main comparison. Bisphosphonates compared to placebo/no treatment for advanced prostate cancer
Comparison 1. Bisphosphonates versus control

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Proportion of participants with pain response Show forest plot

3

876

Risk Ratio (M‐H, Fixed, 95% CI)

1.15 [0.93, 1.43]

2 Skeletal‐related events: any Show forest plot

9

3153

Risk Ratio (M‐H, Fixed, 95% CI)

0.87 [0.81, 0.94]

3 Skeletal‐related events: pathologic fracture Show forest plot

6

2226

Risk Ratio (M‐H, Fixed, 95% CI)

0.68 [0.53, 0.87]

4 Skeletal‐related events: pathologic fractures: vertebral fracture Show forest plot

2

993

Risk Ratio (M‐H, Fixed, 95% CI)

0.84 [0.52, 1.36]

5 Skeletal‐related events: pathologic fractures: non‐vertebral fracture Show forest plot

2

993

Risk Ratio (M‐H, Fixed, 95% CI)

0.76 [0.53, 1.10]

6 Skeletal‐related events: spinal cord compression Show forest plot

6

2226

Risk Ratio (M‐H, Fixed, 95% CI)

0.67 [0.50, 0.89]

7 Skeletal‐related events: bone radiation therapy Show forest plot

6

1696

Risk Ratio (M‐H, Fixed, 95% CI)

0.90 [0.77, 1.06]

8 Skeletal‐related events: bone surgery Show forest plot

5

1915

Risk Ratio (M‐H, Fixed, 95% CI)

0.50 [0.29, 0.86]

9 Mortality Show forest plot

9

2450

Risk Ratio (M‐H, Fixed, 95% CI)

0.97 [0.91, 1.04]

10 Adverse events: nausea Show forest plot

9

3008

Risk Ratio (M‐H, Fixed, 95% CI)

1.19 [1.00, 1.41]

11 Adverse events: renal Show forest plot

7

1794

Risk Ratio (M‐H, Fixed, 95% CI)

1.65 [1.11, 2.46]

12 Adverse events: bone pain Show forest plot

5

1445

Risk Ratio (M‐H, Fixed, 95% CI)

0.93 [0.81, 1.06]

13 Adverse events: osteonecrosis of the jaw Show forest plot

5

1626

Risk Ratio (M‐H, Fixed, 95% CI)

1.92 [0.75, 4.90]

14 Proportion of participants with decreased analgesic consumption Show forest plot

4

416

Risk Ratio (M‐H, Fixed, 95% CI)

1.19 [0.87, 1.63]

15 Proportion of participants with disease progression Show forest plot

7

2115

Risk Ratio (M‐H, Fixed, 95% CI)

0.94 [0.90, 0.98]

16 Sensitivity analysis: pain response (low risk of bias vs high risk of bias) Show forest plot

3

876

Risk Ratio (M‐H, Fixed, 95% CI)

1.15 [0.93, 1.43]

16.1 Low risk of bias

1

227

Risk Ratio (M‐H, Fixed, 95% CI)

1.23 [0.80, 1.89]

16.2 High risk of bias

2

649

Risk Ratio (M‐H, Fixed, 95% CI)

1.13 [0.88, 1.44]

17 Subgroup analysis: pain response (amino‐bisphosphonate vs non‐amino‐bisphosphonate) Show forest plot

3

876

Risk Ratio (M‐H, Fixed, 95% CI)

1.15 [0.93, 1.43]

17.1 Amino‐bisphosphonate

1

592

Risk Ratio (M‐H, Fixed, 95% CI)

1.12 [0.87, 1.44]

17.2 Non‐amino‐bisphosphonate

2

284

Risk Ratio (M‐H, Fixed, 95% CI)

1.23 [0.81, 1.87]

18 Subgroup analysis: pain response (route of administration) Show forest plot

3

876

Risk Ratio (M‐H, Fixed, 95% CI)

1.15 [0.93, 1.43]

18.1 Oral

1

592

Risk Ratio (M‐H, Fixed, 95% CI)

1.12 [0.87, 1.44]

18.2 Intravenous

2

284

Risk Ratio (M‐H, Fixed, 95% CI)

1.23 [0.81, 1.87]

19 Sensitivity analysis: skeletal‐related events (low risk of bias vs high risk of bias) Show forest plot

9

3153

Risk Ratio (M‐H, Fixed, 95% CI)

0.87 [0.81, 0.94]

19.1 Low risk of bias

5

1767

Risk Ratio (M‐H, Fixed, 95% CI)

0.90 [0.81, 0.99]

19.2 High risk of bias

4

1386

Risk Ratio (M‐H, Fixed, 95% CI)

0.84 [0.75, 0.94]

20 Sensitivity analysis: skeletal‐related events (full‐text vs abstract publication) Show forest plot

9

3153

Risk Ratio (M‐H, Fixed, 95% CI)

0.87 [0.81, 0.94]

20.1 Full‐text publication

8

3093

Risk Ratio (M‐H, Fixed, 95% CI)

0.88 [0.81, 0.95]

20.2 Abstract publication

1

60

Risk Ratio (M‐H, Fixed, 95% CI)

0.40 [0.12, 1.37]

21 Subgroup analysis: skeletal‐related events (amino‐bisphosphonate versus non‐amino‐bisphosphonate) Show forest plot

9

3153

Risk Ratio (M‐H, Fixed, 95% CI)

0.87 [0.81, 0.94]

21.1 Amino‐bisphosphonate

8

2842

Risk Ratio (M‐H, Fixed, 95% CI)

0.86 [0.79, 0.94]

21.2 Non‐amino‐bisphosphonate

1

311

Risk Ratio (M‐H, Fixed, 95% CI)

0.92 [0.78, 1.09]

22 Subgroup analysis: skeletal‐related events (route of administration) Show forest plot

9

3153

Risk Ratio (M‐H, Fixed, 95% CI)

0.87 [0.81, 0.94]

22.1 Oral

2

374

Risk Ratio (M‐H, Fixed, 95% CI)

0.92 [0.78, 1.09]

22.2 Intravenous

7

2779

Risk Ratio (M‐H, Fixed, 95% CI)

0.86 [0.79, 0.94]

23 Sensitivity analysis: mortality (low risk of bias vs high risk of bias)) Show forest plot

9

2450

Risk Ratio (M‐H, Fixed, 95% CI)

0.97 [0.91, 1.04]

23.1 Low risk of bias

6

1420

Risk Ratio (M‐H, Fixed, 95% CI)

0.93 [0.85, 1.02]

23.2 High risk of bias

3

1030

Risk Ratio (M‐H, Fixed, 95% CI)

1.04 [0.94, 1.15]

24 Sensitivity analysis: mortality (full‐text vs abstract publication) Show forest plot

9

2450

Risk Ratio (M‐H, Fixed, 95% CI)

0.97 [0.91, 1.04]

24.1 Full‐text publication

8

2390

Risk Ratio (M‐H, Fixed, 95% CI)

0.98 [0.91, 1.04]

24.2 Abstract publication

1

60

Risk Ratio (M‐H, Fixed, 95% CI)

0.80 [0.32, 2.03]

25 Subgroup analysis: mortality (amino‐bisphosphonate vs non‐amino‐bisphosphonate) Show forest plot

9

2450

Risk Ratio (M‐H, Fixed, 95% CI)

0.97 [0.91, 1.04]

25.1 Amino‐bisphosphonate

5

1738

Risk Ratio (M‐H, Fixed, 95% CI)

0.98 [0.90, 1.07]

25.2 Non‐amino‐bisphosphonate

4

712

Risk Ratio (M‐H, Fixed, 95% CI)

0.96 [0.87, 1.06]

26 Subgroup analysis: mortality (route of administration) Show forest plot

9

2450

Risk Ratio (M‐H, Fixed, 95% CI)

0.97 [0.91, 1.04]

26.1 Oral

5

1140

Risk Ratio (M‐H, Fixed, 95% CI)

1.02 [0.95, 1.11]

26.2 Intravenous

4

1310

Risk Ratio (M‐H, Fixed, 95% CI)

0.91 [0.81, 1.02]

27 Sensitivity analysis: adverse event: nausea (low risk of bias vs high risk of bias) Show forest plot

9

3008

Risk Ratio (M‐H, Fixed, 95% CI)

1.19 [1.00, 1.41]

27.1 Low risk of bias

7

2042

Risk Ratio (M‐H, Fixed, 95% CI)

1.18 [0.99, 1.40]

27.2 High risk of bias

2

966

Risk Ratio (M‐H, Fixed, 95% CI)

1.41 [0.49, 4.03]

28 Subgroup analysis: adverse event: nausea (amino‐bisphosphonate vs non‐amino‐bisphosphonate) Show forest plot

9

3008

Risk Ratio (M‐H, Fixed, 95% CI)

1.19 [1.00, 1.41]

28.1 Amino‐bisphosphonate

5

2332

Risk Ratio (M‐H, Fixed, 95% CI)

1.19 [0.98, 1.45]

28.2 Non‐amino‐bisphosphonate

4

676

Risk Ratio (M‐H, Fixed, 95% CI)

1.18 [0.83, 1.68]

29 Subgroup analysis: adverse event: nausea (route of administration) Show forest plot

9

3008

Risk Ratio (M‐H, Fixed, 95% CI)

1.19 [1.00, 1.41]

29.1 Oral

4

1059

Risk Ratio (M‐H, Fixed, 95% CI)

1.15 [0.80, 1.67]

29.2 Intravenous

5

1949

Risk Ratio (M‐H, Fixed, 95% CI)

1.20 [0.99, 1.45]

30 Sensitivity analysis: renal (low risk of bias vs high risk of bias) Show forest plot

7

1794

Risk Ratio (M‐H, Fixed, 95% CI)

1.65 [1.11, 2.46]

30.1 Low risk of bias

5

1498

Risk Ratio (M‐H, Fixed, 95% CI)

1.59 [1.06, 2.40]

30.2 High risk of bias

2

296

Risk Ratio (M‐H, Fixed, 95% CI)

3.0 [0.48, 18.65]

31 Subgroup analysis: renal (amino‐bisphosphonate vs non‐amino‐bisphosphonate) Show forest plot

7

1794

Risk Ratio (M‐H, Fixed, 95% CI)

1.65 [1.11, 2.46]

31.1 Amino‐bisphosphonate

5

1662

Risk Ratio (M‐H, Fixed, 95% CI)

1.63 [1.09, 2.44]

31.2 Non‐amino‐bisphosphonate

2

132

Risk Ratio (M‐H, Fixed, 95% CI)

3.24 [0.14, 77.15]

32 Subgroup analysis: renal (route of administration) Show forest plot

7

1794

Risk Ratio (M‐H, Fixed, 95% CI)

1.65 [1.11, 2.46]

32.1 Oral

3

204

Risk Ratio (M‐H, Fixed, 95% CI)

2.40 [0.37, 15.75]

32.2 Intravenous

4

1590

Risk Ratio (M‐H, Fixed, 95% CI)

1.62 [1.07, 2.44]

Figures and Tables -
Comparison 1. Bisphosphonates versus control