Bisphosphonates for osteoporosis in people with cystic fibrosis

Louise S Conwell; Anne B Chang

doi:10.1002/14651858.CD002010.pub2

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$Comparison 1 Bisphosphonates versus control (without lung transplantation), Outcome 1 Vertebral fractures.$

Analysis 1.1

Comparison 1 Bisphosphonates versus control (without lung transplantation), Outcome 1 Vertebral fractures.

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$Comparison 1 Bisphosphonates versus control (without lung transplantation), Outcome 2 Non‐vertebral fractures.$

Analysis 1.2

Comparison 1 Bisphosphonates versus control (without lung transplantation), Outcome 2 Non‐vertebral fractures.

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Analysis 1.3

Comparison 1 Bisphosphonates versus control (without lung transplantation), Outcome 3 Total Fractures.

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Analysis 1.4

Comparison 1 Bisphosphonates versus control (without lung transplantation), Outcome 4 Percent change in BMD, lumbar spine, DXA (Time‐points).

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Analysis 1.5

Comparison 1 Bisphosphonates versus control (without lung transplantation), Outcome 5 Percent change in BMD, lumbar spine, DXA (End of study).

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Analysis 1.6

Comparison 1 Bisphosphonates versus control (without lung transplantation), Outcome 6 Percent change in BMD, total hip / femur, DXA (Time‐points).

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Analysis 1.7

Comparison 1 Bisphosphonates versus control (without lung transplantation), Outcome 7 Percent change in BMD, total hip/femur, DXA (End of study).

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Analysis 1.8

Comparison 1 Bisphosphonates versus control (without lung transplantation), Outcome 8 Percent change in BMD, distal radius, SXA (Time‐points).

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Analysis 1.9

Comparison 1 Bisphosphonates versus control (without lung transplantation), Outcome 9 Percent change in BMD, distal radius, SXA (End of study).

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Analysis 1.10

Comparison 1 Bisphosphonates versus control (without lung transplantation), Outcome 10 Percent change in BMD, ultradistal radius, SXA.

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Analysis 1.11

Comparison 1 Bisphosphonates versus control (without lung transplantation), Outcome 11 Bone pain.

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Analysis 1.12

Comparison 1 Bisphosphonates versus control (without lung transplantation), Outcome 12 Fever.

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Analysis 1.13

Comparison 1 Bisphosphonates versus control (without lung transplantation), Outcome 13 Withdrawals, due to adverse events.

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Analysis 1.14

Comparison 1 Bisphosphonates versus control (without lung transplantation), Outcome 14 Withdrawals, total.

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Analysis 1.15

Comparison 1 Bisphosphonates versus control (without lung transplantation), Outcome 15 Survival.

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$Comparison 2 Bisphosphonates versus control (with lung transplantation), Outcome 1 Vertebral fractures.$

Analysis 2.1

Comparison 2 Bisphosphonates versus control (with lung transplantation), Outcome 1 Vertebral fractures.

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$Comparison 2 Bisphosphonates versus control (with lung transplantation), Outcome 2 Non‐vertebral fractures.$

Analysis 2.2

Comparison 2 Bisphosphonates versus control (with lung transplantation), Outcome 2 Non‐vertebral fractures.

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Analysis 2.3

Comparison 2 Bisphosphonates versus control (with lung transplantation), Outcome 3 Total Fractures.

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Analysis 2.4

Comparison 2 Bisphosphonates versus control (with lung transplantation), Outcome 4 Percent change in BMD, lumbar spine, DXA.

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Analysis 2.5

Comparison 2 Bisphosphonates versus control (with lung transplantation), Outcome 5 Percent change in BMD, femur, DXA.

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Analysis 2.6

Comparison 2 Bisphosphonates versus control (with lung transplantation), Outcome 6 Bone pain.

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Analysis 2.7

Comparison 2 Bisphosphonates versus control (with lung transplantation), Outcome 7 Withdrawals, due to adverse events.

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Analysis 2.8

Comparison 2 Bisphosphonates versus control (with lung transplantation), Outcome 8 Withdrawals, total.

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Analysis 2.9

Comparison 2 Bisphosphonates versus control (with lung transplantation), Outcome 9 Survival.

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Comparison 1. Bisphosphonates versus control (without lung transplantation)

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Vertebral fractures Show forest plot	2		Odds Ratio (M‐H, Fixed, 95% CI)	Subtotals only

1.1 12 months	2	60	Odds Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
1.2 24 months	1	20	Odds Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
2 Non‐vertebral fractures Show forest plot	2		Odds Ratio (M‐H, Fixed, 95% CI)	Subtotals only

2.1 12 months	2	60	Odds Ratio (M‐H, Fixed, 95% CI)	2.11 [0.18, 25.35]
2.2 24 months	1	20	Odds Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
3 Total Fractures Show forest plot	2		Odds Ratio (M‐H, Fixed, 95% CI)	Subtotals only

3.1 12 months	2	60	Odds Ratio (M‐H, Fixed, 95% CI)	2.11 [0.18, 25.35]
3.2 24 months	1	20	Odds Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
4 Percent change in BMD, lumbar spine, DXA (Time‐points) Show forest plot	4		Mean Difference (IV, Fixed, 95% CI)	Subtotals only

4.1 6 months	4	101	Mean Difference (IV, Fixed, 95% CI)	4.61 [3.90, 5.32]
4.2 12 months	2	59	Mean Difference (IV, Fixed, 95% CI)	6.38 [5.21, 7.54]
4.3 24 months	1	19	Mean Difference (IV, Fixed, 95% CI)	5.70 [4.55, 6.85]
5 Percent change in BMD, lumbar spine, DXA (End of study) Show forest plot	4		Mean Difference (IV, Fixed, 95% CI)	Subtotals only

5.1 End of study	4	92	Mean Difference (IV, Fixed, 95% CI)	5.90 [4.94, 6.87]
6 Percent change in BMD, total hip / femur, DXA (Time‐points) Show forest plot	3		Mean Difference (IV, Random, 95% CI)	Subtotals only

6.1 6 months	3	96	Mean Difference (IV, Random, 95% CI)	3.35 [1.63, 5.07]
6.2 12 months	2	59	Mean Difference (IV, Random, 95% CI)	4.84 [2.73, 6.96]
6.3 24 months	1	19	Mean Difference (IV, Random, 95% CI)	6.73 [5.51, 7.95]
7 Percent change in BMD, total hip/femur, DXA (End of study) Show forest plot	3		Mean Difference (IV, Random, 95% CI)	Subtotals only

7.1 End of study	3	87	Mean Difference (IV, Random, 95% CI)	4.58 [1.92, 7.24]
8 Percent change in BMD, distal radius, SXA (Time‐points) Show forest plot	2		Mean Difference (IV, Random, 95% CI)	Subtotals only

8.1 6 months	2	48	Mean Difference (IV, Random, 95% CI)	‐0.49 [‐2.42, 1.45]
8.2 12 months	1	18	Mean Difference (IV, Random, 95% CI)	0.32 [‐0.30, 0.94]
8.3 24 months	1	14	Mean Difference (IV, Random, 95% CI)	1.5 [0.41, 2.59]
9 Percent change in BMD, distal radius, SXA (End of study) Show forest plot	2		Mean Difference (IV, Random, 95% CI)	Subtotals only

9.1 End of study	2	42	Mean Difference (IV, Random, 95% CI)	0.01 [‐3.12, 3.14]
10 Percent change in BMD, ultradistal radius, SXA Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

10.1 6 months	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
11 Bone pain Show forest plot	4		Odds Ratio (M‐H, Fixed, 95% CI)	Subtotals only

11.1 Oral bisphosphonates	1	48	Odds Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
11.2 Intravenous bisphosphonates	3	60	Odds Ratio (M‐H, Fixed, 95% CI)	14.17 [3.64, 55.17]
11.3 All routes of bisphosphonate administration	4	108	Odds Ratio (M‐H, Fixed, 95% CI)	14.17 [3.64, 55.17]
12 Fever Show forest plot	4		Odds Ratio (M‐H, Fixed, 95% CI)	Subtotals only

12.1 Oral bisphosphonates	1	48	Odds Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
12.2 Intravenous bisphosphonates	3	55	Odds Ratio (M‐H, Fixed, 95% CI)	12.64 [2.31, 69.11]
12.3 All routes of bisphosphonate administration	4	103	Odds Ratio (M‐H, Fixed, 95% CI)	12.64 [2.31, 69.11]
13 Withdrawals, due to adverse events Show forest plot	3		Odds Ratio (M‐H, Fixed, 95% CI)	Subtotals only

13.1 6 months	2	53	Odds Ratio (M‐H, Fixed, 95% CI)	3.95 [0.14, 108.09]
13.2 12 months	2	70	Odds Ratio (M‐H, Fixed, 95% CI)	7.35 [0.31, 173.13]
13.3 24 months	1	22	Odds Ratio (M‐H, Fixed, 95% CI)	7.35 [0.31, 173.13]
14 Withdrawals, total Show forest plot	3		Odds Ratio (M‐H, Fixed, 95% CI)	Subtotals only

14.1 6 months	2	53	Odds Ratio (M‐H, Fixed, 95% CI)	2.83 [0.39, 20.73]
14.2 12 months	2	70	Odds Ratio (M‐H, Fixed, 95% CI)	1.08 [0.31, 3.73]
14.3 24 months	1	22	Odds Ratio (M‐H, Fixed, 95% CI)	0.43 [0.07, 2.50]
15 Survival Show forest plot	4		Odds Ratio (M‐H, Fixed, 95% CI)	Subtotals only

15.1 6 months	2	36	Odds Ratio (M‐H, Fixed, 95% CI)	0.93 [0.05, 16.39]
15.2 12 months	1	48	Odds Ratio (M‐H, Fixed, 95% CI)	3.13 [0.12, 80.68]
15.3 24 months	1	22	Odds Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]

Comparison 1. Bisphosphonates versus control (without lung transplantation)

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Comparison 2. Bisphosphonates versus control (with lung transplantation)

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Vertebral fractures Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected

1.1 24 months	1		Odds Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
2 Non‐vertebral fractures Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected

2.1 24 months	1		Odds Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
3 Total Fractures Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected

3.1 24 months	1		Odds Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
4 Percent change in BMD, lumbar spine, DXA Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

4.1 24 months	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
5 Percent change in BMD, femur, DXA Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

5.1 24 months	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
6 Bone pain Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected

6.1 24 months	1		Odds Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
7 Withdrawals, due to adverse events Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected

8 Withdrawals, total Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected

8.1 24 months	1		Odds Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
9 Survival Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected

9.1 24 months	1		Odds Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]

Comparison 2. Bisphosphonates versus control (with lung transplantation)

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