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. 2017 Dec 26;2017(12):CD006250. doi: 10.1002/14651858.CD006250.pub2

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 3 876 Risk Ratio (M‐H, Fixed, 95% CI) 1.15 [0.93, 1.43]
2 Skeletal‐related events: any 9 3153 Risk Ratio (M‐H, Fixed, 95% CI) 0.87 [0.81, 0.94]
3 Skeletal‐related events: pathologic fracture 6 2226 Risk Ratio (M‐H, Fixed, 95% CI) 0.68 [0.53, 0.87]
4 Skeletal‐related events: pathologic fractures: vertebral fracture 2 993 Risk Ratio (M‐H, Fixed, 95% CI) 0.84 [0.52, 1.36]
5 Skeletal‐related events: pathologic fractures: non‐vertebral fracture 2 993 Risk Ratio (M‐H, Fixed, 95% CI) 0.76 [0.53, 1.10]
6 Skeletal‐related events: spinal cord compression 6 2226 Risk Ratio (M‐H, Fixed, 95% CI) 0.67 [0.50, 0.89]
7 Skeletal‐related events: bone radiation therapy 6 1696 Risk Ratio (M‐H, Fixed, 95% CI) 0.90 [0.77, 1.06]
8 Skeletal‐related events: bone surgery 5 1915 Risk Ratio (M‐H, Fixed, 95% CI) 0.50 [0.29, 0.86]
9 Mortality 9 2450 Risk Ratio (M‐H, Fixed, 95% CI) 0.97 [0.91, 1.04]
10 Adverse events: nausea 9 3008 Risk Ratio (M‐H, Fixed, 95% CI) 1.19 [1.00, 1.41]
11 Adverse events: renal 7 1794 Risk Ratio (M‐H, Fixed, 95% CI) 1.65 [1.11, 2.46]
12 Adverse events: bone pain 5 1445 Risk Ratio (M‐H, Fixed, 95% CI) 0.93 [0.81, 1.06]
13 Adverse events: osteonecrosis of the jaw 5 1626 Risk Ratio (M‐H, Fixed, 95% CI) 1.92 [0.75, 4.90]
14 Proportion of participants with decreased analgesic consumption 4 416 Risk Ratio (M‐H, Fixed, 95% CI) 1.19 [0.87, 1.63]
15 Proportion of participants with disease progression 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) 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) 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) 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) 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) 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) 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) 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)) 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) 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) 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) 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) 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) 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) 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) 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) 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) 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]