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Bisfosfonati za osteoporozu kod osoba s cističnom fibrozom

Appendices

Appendix 1. Additional electronic search strategies

Strategies for current version of this review

Database

Search strategy

Date last searched

PubMed (all years to date of search)

#1 cystic fibrosis OR mucoviscidosis OR mucoviscidose

#2 Biphosphonate OR Diphosphonate OR alendronate OR pamidronate OR etidronate OR Etidronic OR clodronate OR clodronic OR tiludronate OR olpadronate OR incadronate OR risedronate OR risedronic OR zoledronate OR zolendronic OR elodronate OR ibandronate

#3 #1 AND #2

#4 randomized controlled trial [pt]

#5 controlled clinical trial [pt]

#6 randomized [tiab]

#7 placebo [tiab]

#8 drug therapy [sh]

#9 randomly [tiab]

#10 trial [tiab]

#11 groups [tiab]

#12 #4 OR #5 OR #6 OR #7 OR #8 OR #9 OR #10 OR #11

#13 animals [mh] NOT humans [mh] 

#14 #12 NOT #13

#15 #3 AND #14

 

Note: lines #4 to #14 is the Cochrane Highly Sensitive Search Strategy for identifying randomised trials in MEDLINE: sensitivity‐maximising version (2008 revision); PubMed format (training.cochrane.org/handbook/version-6/chapter-4-tech-suppl, page 60)

5 May 2022

ClinicalTrials.gov

(clinicaltrials.gov)

[Advanced search]

 

Condition or disease: cystic fibrosis OR mucoviscidosis OR mucoviscidose

 

Other terms: Biphosphonate OR Diphosphonate OR alendronate OR pamidronate OR etidronate OR Etidronic OR clodronate OR clodronic OR tiludronate OR olpadronate OR incadronate OR risedronate OR risedronic OR zoledronate OR zolendronic OR elodronate OR ibandronate

 

Study type: Interventional Studies (Clinical Trials)

5 May 2022

WHO International Clinical Trials Registry Platform (ICTRP)

(trialsearch.who.int)

[Advanced search]

 

Condition: cystic fibrosis OR mucoviscidosis OR mucoviscidose

 

Intervention: Biphosphonate OR Diphosphonate OR alendronate OR pamidronate OR etidronate OR Etidronic OR clodronate OR clodronic OR tiludronate OR olpadronate OR incadronate OR risedronate OR risedronic OR zoledronate OR zolendronic OR elodronate OR ibandronate

 

Recruitment status: All

5 May 2022

Strategies for previous versions of this review

Database

Search strategy

Date last searched

PubMed

(all years up to date)

zoledronate AND cystic fibrosis

OR

"Diphosphonates" [Mesh] AND "Cystic Fibrosis" [Mesh]

14 January 2014

Selection process for this update.

Figuras y tablas -
Figure 1

Selection process for this update.

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.

Figuras y tablas -
Figure 2

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.

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

Figuras y tablas -
Figure 3

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

Forest plot of comparison between bisphosphonates versus control (without lung transplantation), Outcome 1a Number of participants with any fracture.

Figuras y tablas -
Figure 4

Forest plot of comparison between bisphosphonates versus control (without lung transplantation), Outcome 1a Number of participants with any fracture.

Forest plot of comparison between bisphosphonates versus control (without lung transplantation), Outcome 1b i. Number of participants with non‐vertebral fractures.

Figuras y tablas -
Figure 5

Forest plot of comparison between bisphosphonates versus control (without lung transplantation), Outcome 1b i. Number of participants with non‐vertebral fractures.

Forest plot of comparison between bisphosphonates versus control (without lung transplantation), Outcome 1b ii. Number of participants with vertebral fractures.

Figuras y tablas -
Figure 6

Forest plot of comparison between bisphosphonates versus control (without lung transplantation), Outcome 1b ii. Number of participants with vertebral fractures.

Comparison 1: Bisphosphonates versus control (without lung transplantation) ‐ adults (18 years and over), Outcome 1: Total fractures

Figuras y tablas -
Analysis 1.1

Comparison 1: Bisphosphonates versus control (without lung transplantation) ‐ adults (18 years and over), Outcome 1: Total fractures

Comparison 1: Bisphosphonates versus control (without lung transplantation) ‐ adults (18 years and over), Outcome 2: Non‐vertebral fractures

Figuras y tablas -
Analysis 1.2

Comparison 1: Bisphosphonates versus control (without lung transplantation) ‐ adults (18 years and over), Outcome 2: Non‐vertebral fractures

Comparison 1: Bisphosphonates versus control (without lung transplantation) ‐ adults (18 years and over), Outcome 3: Vertebral fractures

Figuras y tablas -
Analysis 1.3

Comparison 1: Bisphosphonates versus control (without lung transplantation) ‐ adults (18 years and over), Outcome 3: Vertebral fractures

Comparison 1: Bisphosphonates versus control (without lung transplantation) ‐ adults (18 years and over), Outcome 4: % change in BMD, lumbar spine [DXA]

Figuras y tablas -
Analysis 1.4

Comparison 1: Bisphosphonates versus control (without lung transplantation) ‐ adults (18 years and over), Outcome 4: % change in BMD, lumbar spine [DXA]

Comparison 1: Bisphosphonates versus control (without lung transplantation) ‐ adults (18 years and over), Outcome 5: % change in BMD, lumbar spine [DXA] (end of trial data only)

Figuras y tablas -
Analysis 1.5

Comparison 1: Bisphosphonates versus control (without lung transplantation) ‐ adults (18 years and over), Outcome 5: % change in BMD, lumbar spine [DXA] (end of trial data only)

Comparison 1: Bisphosphonates versus control (without lung transplantation) ‐ adults (18 years and over), Outcome 6: % change in BMD, total hip/femur [DXA]

Figuras y tablas -
Analysis 1.6

Comparison 1: Bisphosphonates versus control (without lung transplantation) ‐ adults (18 years and over), Outcome 6: % change in BMD, total hip/femur [DXA]

Comparison 1: Bisphosphonates versus control (without lung transplantation) ‐ adults (18 years and over), Outcome 7: % change in BMD, total hip/femur [DXA] (end of trial data only)

Figuras y tablas -
Analysis 1.7

Comparison 1: Bisphosphonates versus control (without lung transplantation) ‐ adults (18 years and over), Outcome 7: % change in BMD, total hip/femur [DXA] (end of trial data only)

Comparison 1: Bisphosphonates versus control (without lung transplantation) ‐ adults (18 years and over), Outcome 8: % change in BMD, distal radius [SXA]

Figuras y tablas -
Analysis 1.8

Comparison 1: Bisphosphonates versus control (without lung transplantation) ‐ adults (18 years and over), Outcome 8: % change in BMD, distal radius [SXA]

Comparison 1: Bisphosphonates versus control (without lung transplantation) ‐ adults (18 years and over), Outcome 9: % change in BMD, distal radius [SXA] (end of trial data only)

Figuras y tablas -
Analysis 1.9

Comparison 1: Bisphosphonates versus control (without lung transplantation) ‐ adults (18 years and over), Outcome 9: % change in BMD, distal radius [SXA] (end of trial data only)

Comparison 1: Bisphosphonates versus control (without lung transplantation) ‐ adults (18 years and over), Outcome 10: % change in BMD, ultra distal radius [SXA]

Figuras y tablas -
Analysis 1.10

Comparison 1: Bisphosphonates versus control (without lung transplantation) ‐ adults (18 years and over), Outcome 10: % change in BMD, ultra distal radius [SXA]

Comparison 1: Bisphosphonates versus control (without lung transplantation) ‐ adults (18 years and over), Outcome 11: QoL

Figuras y tablas -
Analysis 1.11

Comparison 1: Bisphosphonates versus control (without lung transplantation) ‐ adults (18 years and over), Outcome 11: QoL

Comparison 1: Bisphosphonates versus control (without lung transplantation) ‐ adults (18 years and over), Outcome 12: Bone pain

Figuras y tablas -
Analysis 1.12

Comparison 1: Bisphosphonates versus control (without lung transplantation) ‐ adults (18 years and over), Outcome 12: Bone pain

Comparison 1: Bisphosphonates versus control (without lung transplantation) ‐ adults (18 years and over), Outcome 13: Fever

Figuras y tablas -
Analysis 1.13

Comparison 1: Bisphosphonates versus control (without lung transplantation) ‐ adults (18 years and over), Outcome 13: Fever

Comparison 1: Bisphosphonates versus control (without lung transplantation) ‐ adults (18 years and over), Outcome 14: Withdrawals due to adverse events

Figuras y tablas -
Analysis 1.14

Comparison 1: Bisphosphonates versus control (without lung transplantation) ‐ adults (18 years and over), Outcome 14: Withdrawals due to adverse events

Comparison 1: Bisphosphonates versus control (without lung transplantation) ‐ adults (18 years and over), Outcome 15: Withdrawals (total)

Figuras y tablas -
Analysis 1.15

Comparison 1: Bisphosphonates versus control (without lung transplantation) ‐ adults (18 years and over), Outcome 15: Withdrawals (total)

Comparison 1: Bisphosphonates versus control (without lung transplantation) ‐ adults (18 years and over), Outcome 16: Survival

Figuras y tablas -
Analysis 1.16

Comparison 1: Bisphosphonates versus control (without lung transplantation) ‐ adults (18 years and over), Outcome 16: Survival

Comparison 2: Bisphosphonates versus control (without lung transplantation) ‐ children up to 18 years of age, Outcome 1: Total fractures

Figuras y tablas -
Analysis 2.1

Comparison 2: Bisphosphonates versus control (without lung transplantation) ‐ children up to 18 years of age, Outcome 1: Total fractures

Comparison 2: Bisphosphonates versus control (without lung transplantation) ‐ children up to 18 years of age, Outcome 2: Non‐vertebral fractures

Figuras y tablas -
Analysis 2.2

Comparison 2: Bisphosphonates versus control (without lung transplantation) ‐ children up to 18 years of age, Outcome 2: Non‐vertebral fractures

Comparison 2: Bisphosphonates versus control (without lung transplantation) ‐ children up to 18 years of age, Outcome 3: Vertebral fractures

Figuras y tablas -
Analysis 2.3

Comparison 2: Bisphosphonates versus control (without lung transplantation) ‐ children up to 18 years of age, Outcome 3: Vertebral fractures

Comparison 2: Bisphosphonates versus control (without lung transplantation) ‐ children up to 18 years of age, Outcome 4: % change in BMD, lumbar spine, DXA

Figuras y tablas -
Analysis 2.4

Comparison 2: Bisphosphonates versus control (without lung transplantation) ‐ children up to 18 years of age, Outcome 4: % change in BMD, lumbar spine, DXA

Comparison 2: Bisphosphonates versus control (without lung transplantation) ‐ children up to 18 years of age, Outcome 5: Bone or muscle pain

Figuras y tablas -
Analysis 2.5

Comparison 2: Bisphosphonates versus control (without lung transplantation) ‐ children up to 18 years of age, Outcome 5: Bone or muscle pain

Comparison 2: Bisphosphonates versus control (without lung transplantation) ‐ children up to 18 years of age, Outcome 6: Fever

Figuras y tablas -
Analysis 2.6

Comparison 2: Bisphosphonates versus control (without lung transplantation) ‐ children up to 18 years of age, Outcome 6: Fever

Comparison 2: Bisphosphonates versus control (without lung transplantation) ‐ children up to 18 years of age, Outcome 7: Gastrointestinal adverse events

Figuras y tablas -
Analysis 2.7

Comparison 2: Bisphosphonates versus control (without lung transplantation) ‐ children up to 18 years of age, Outcome 7: Gastrointestinal adverse events

Comparison 2: Bisphosphonates versus control (without lung transplantation) ‐ children up to 18 years of age, Outcome 8: Headache

Figuras y tablas -
Analysis 2.8

Comparison 2: Bisphosphonates versus control (without lung transplantation) ‐ children up to 18 years of age, Outcome 8: Headache

Comparison 2: Bisphosphonates versus control (without lung transplantation) ‐ children up to 18 years of age, Outcome 9: Any adverse event

Figuras y tablas -
Analysis 2.9

Comparison 2: Bisphosphonates versus control (without lung transplantation) ‐ children up to 18 years of age, Outcome 9: Any adverse event

Comparison 2: Bisphosphonates versus control (without lung transplantation) ‐ children up to 18 years of age, Outcome 10: Withdrawals, due to adverse events

Figuras y tablas -
Analysis 2.10

Comparison 2: Bisphosphonates versus control (without lung transplantation) ‐ children up to 18 years of age, Outcome 10: Withdrawals, due to adverse events

Comparison 2: Bisphosphonates versus control (without lung transplantation) ‐ children up to 18 years of age, Outcome 11: Withdrawals, total

Figuras y tablas -
Analysis 2.11

Comparison 2: Bisphosphonates versus control (without lung transplantation) ‐ children up to 18 years of age, Outcome 11: Withdrawals, total

Comparison 2: Bisphosphonates versus control (without lung transplantation) ‐ children up to 18 years of age, Outcome 12: Survival

Figuras y tablas -
Analysis 2.12

Comparison 2: Bisphosphonates versus control (without lung transplantation) ‐ children up to 18 years of age, Outcome 12: Survival

Comparison 3: Bisphosphonates versus control (with lung transplantation) ‐ adults (18 years and over), Outcome 1: Total Fractures

Figuras y tablas -
Analysis 3.1

Comparison 3: Bisphosphonates versus control (with lung transplantation) ‐ adults (18 years and over), Outcome 1: Total Fractures

Comparison 3: Bisphosphonates versus control (with lung transplantation) ‐ adults (18 years and over), Outcome 2: Non‐vertebral fractures

Figuras y tablas -
Analysis 3.2

Comparison 3: Bisphosphonates versus control (with lung transplantation) ‐ adults (18 years and over), Outcome 2: Non‐vertebral fractures

Comparison 3: Bisphosphonates versus control (with lung transplantation) ‐ adults (18 years and over), Outcome 3: Vertebral fractures

Figuras y tablas -
Analysis 3.3

Comparison 3: Bisphosphonates versus control (with lung transplantation) ‐ adults (18 years and over), Outcome 3: Vertebral fractures

Comparison 3: Bisphosphonates versus control (with lung transplantation) ‐ adults (18 years and over), Outcome 4: % change in BMD, lumbar spine, DXA

Figuras y tablas -
Analysis 3.4

Comparison 3: Bisphosphonates versus control (with lung transplantation) ‐ adults (18 years and over), Outcome 4: % change in BMD, lumbar spine, DXA

Comparison 3: Bisphosphonates versus control (with lung transplantation) ‐ adults (18 years and over), Outcome 5: % change in BMD, femur, DXA

Figuras y tablas -
Analysis 3.5

Comparison 3: Bisphosphonates versus control (with lung transplantation) ‐ adults (18 years and over), Outcome 5: % change in BMD, femur, DXA

Comparison 3: Bisphosphonates versus control (with lung transplantation) ‐ adults (18 years and over), Outcome 6: Bone pain

Figuras y tablas -
Analysis 3.6

Comparison 3: Bisphosphonates versus control (with lung transplantation) ‐ adults (18 years and over), Outcome 6: Bone pain

Comparison 3: Bisphosphonates versus control (with lung transplantation) ‐ adults (18 years and over), Outcome 7: Withdrawals, due to adverse events

Figuras y tablas -
Analysis 3.7

Comparison 3: Bisphosphonates versus control (with lung transplantation) ‐ adults (18 years and over), Outcome 7: Withdrawals, due to adverse events

Comparison 3: Bisphosphonates versus control (with lung transplantation) ‐ adults (18 years and over), Outcome 8: Withdrawals, total

Figuras y tablas -
Analysis 3.8

Comparison 3: Bisphosphonates versus control (with lung transplantation) ‐ adults (18 years and over), Outcome 8: Withdrawals, total

Comparison 3: Bisphosphonates versus control (with lung transplantation) ‐ adults (18 years and over), Outcome 9: Survival

Figuras y tablas -
Analysis 3.9

Comparison 3: Bisphosphonates versus control (with lung transplantation) ‐ adults (18 years and over), Outcome 9: Survival

Summary of findings 1. Bisphosphonates compared with control for osteoporosis in people with cystic fibrosis who have not had a lung transplant

Patient or population: adults with cystic fibrosis who have not had a lung transplant

Settings: outpatients
Intervention: bisphosphonatesa

Comparison: placebo or no bisphosphonatesb

Outcomes

Illustrative comparative risks* (95% CI)

Relative 

effect (95% CI)

Number of 

participants

(studies)

Certainty of

the evidence

(GRADE)

Comments

Assumed risk

Corresponding risk

Control

Bisphosphonates

New vertebral fractures

 

Follow‐up: 12 months

42 per 1000

9 per 1000

(1 to 88)

OR 0.22 

(0.02 to 2.09)

142

(5)

⊕⊝⊝⊝

very lowc,d

 

New non‐vertebral fractures

 

Follow‐up: 12 months

21 per 1000

44 per 1000

(4 to 532)

OR 2.11 

(0.18 to 25.35)

95

(4)

⊕⊝⊝⊝

very lowd,e

 

BMD: % change in BMD at the lumbar spine

 

Follow‐up: 12 months

The mean % change in BMD (lumbar spine) ranged across control groups

 from ‐1.8% to 0.7%

The mean % change in BMD in the intervention groups was 6.31% higher (5.39% higher to 7.22% higher)

NA

171

(6)

⊕⊕⊝⊝

lowf

 

BMD: % change in BMD at the hip or femur

 

Follow‐up: 12 months

The mean % change in BMD

(hip or femur) ranged across control groups from ‐2.8% to ‐0.7%

The mean % change in BMD in the intervention groups was 4.41% higher (3.44% higher to 5.37% higher)

NA

155

(5)

⊕⊕⊝⊝

lowf

 

QoL: change in physical and mental component scores (SF36v2)

 

Follow‐up: 12 months

The change in mean (SD) SF36 physical  score was ‐3.69 (8.33) in the control group

The mean change in SF36 physical score in the intervention group was 2.51 higher (1.38 lower to 6.40 higher) than in the control group

NA

47

(1)

⊕⊕⊝⊝

lowd,g

The results for the physical and mental components are heterogeneous

 

The change in mean (SD) SF36 mental score was 3.26 (12.27) in the control group

The mean change in SF36 mental score in the intervention group was 5.93 lower (11.73 lower to 0.13 higher) than in the control group

Adverse events: bone pain (all routes of bisphosphonate administration)

 

Follow‐up: 12 months

38 per 1000

323 per 1000

(122 to 857)

OR 8.49 (3.20 to 22.56)

206

(7)

⊕⊕⊕⊝

moderateh

Bone pain

Separating by route of administration did not change the results; both routes favoured control.

Oral bisphosphonates: MD 4.98 (1.24 to 20.09) and IV bisphosphonates: MD 14.17 (3.64 to 55.17)

 

Fever

Oral route: 2 trials of oral alendronate reported that none of the participants in either group experienced fever

IV route: 3 trials showed that bisphosphonates were associated with a higher occurrence of fever OR 12.64 (2.31 to 69.11)

 

GI adverse effects

Only measured in the oral bisphosphonates trials. At 12 months, 1 trial reported 3 occurrences of diarrhoea (1 in the bisphosphonate group and 2 in the placebo group) (Aris 2004)

1 trial reported no GI adverse effects in either group (Bianchi 2013)

1 trial reported 10 GI adverse events in the bisphosphonates group compared to 7 in the control group (Papaioannou 2008)

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).

BMD: bone mineral density; CI: confidence interval; GI: gastrointestinal; IV: intravenous; MD: mean difference; NA: not applicable; OR: odds ratio; QoL: quality of life; SD: standard deviation; SF36v2: medical outcomes study 36‐item short form.

GRADE Working Group grades of evidence

High certainty: we are very confident that the true effect lies close to that of the estimate of the effect.

Moderate certainty: 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 certainty: our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate of the effect.

Very low certainty: we have very little confidence in the effect estimate; the true effect is likely to be substantially different from the estimate of effect.

aTrials used different types and formulations of bisphosphonates: IV zoledronate (Boyle 2005Chapman 2009); IV pamidronate (Haworth 2001); oral alendronate (Aris 2004Bianchi 2013Krasovsky 2010Papaioannou 2008); oral risedronate (Haworth 2011).
bTrials used different comparators: placebo (Aris 2004Bianchi 2013Boyle 2005Chapman 2009Haworth 2011Papaioannou 2008); no bisphosphonate (cholecalciferol/calcium) (Krasovsky 2010), no bisphosphonate (oral calcium) (Haworth 2001).
cDowngraded twice due to risk of bias across some domains in 5/6 included trials. There were particular concerns around the process of randomisation and allocation concealment in 3 trials and lack of blinding in 1 trial.
dDowngraded once due to imprecision caused by low event rates and small sample size.
eDowngraded twice for risk of bias across some domains of all trials included for this outcome. There were particular concerns around randomisation and allocation concealment.
fDowngraded twice due to risk of bias across 1 or more domains in most of the trials included for this outcome. There were particular concerns around randomisation, allocation concealment, and blinding.
gDowngraded once due to heterogeneity within the results.
hDowngraded once due to risk of bias within the included trials; 3/7 trials were at low risk of bias across most domains and particularly randomisation and allocation concealment therefore we did not feel it necessary to downgrade twice.

Figuras y tablas -
Summary of findings 1. Bisphosphonates compared with control for osteoporosis in people with cystic fibrosis who have not had a lung transplant
Summary of findings 2. Bisphosphonates compared with placebo for osteoporosis in children with cystic fibrosis who have not had a lung transplant

Patient or population: children with cystic fibrosis who have not had a lung transplant

Settings: outpatients

Intervention: oral alendronate plus oral calcifediol and RDA dietary calcium

Comparison: oral placebo plus oral calcifediol and RDA dietary calcium

Outcomes

Illustrative comparative risks* (95% CI)

Relative effect

(95% CI)

Number of 

participants

(studies)

Certainty of the 

evidence

(GRADE)

Comments

Assumed risk

Corresponding risk

Placebo

Bisphosphonates

New vertebral fractures

 

Follow‐up: 12 months

54 per 1000

17 per 1000

(2 to 169)

OR 0.32 (0.03 to 3.13)

113

(1)

⊕⊕⊝⊝

lowa

 

New non‐vertebral fractures

 

Follow‐up: 12 months

36 per 1000

7 per 1000

(1 to 145)

OR 0.19 (0.01 to 4.04)

113

(1)

⊕⊕⊝⊝

lowa

 

BMD: % change in BMD at the lumbar spine

 

Follow‐up: 12 months

The % change in BMD at the lumbar spine was higher in the treatment group than the control group, MD 14.50 (95% CI 12.91 to 16.09)

NA

113

(1)

⊕⊕⊝⊝

lowa

 

BMD: % change in BMD at the hip or femur

This outcome was not reported

 

QoL

This outcome was not reported

 

Adverse events

 

Follow‐up: 12 months

There was no difference in bone or muscle pain, OR 3.00 (95% CI 0.12 to 75.22); fever, OR 3.00 (95% CI 0.12 to 75.22); or GI adverse events OR 0.67 (95% CI 0.20 to 2.26)

NA

113

(1)

⊕⊕⊝⊝

lowa

 

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).

BMD: bone mineral density; CI: confidence interval; GI: gastrointestinal; MD: mean difference; NA: not applicable; OR: odds ratio; QoL: quality of life; RDA: recommended daily allowance.

GRADE Working Group grades of evidence

High certainty: we are very confident that the true effect lies close to that of the estimate of the effect.

Moderate certainty: 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 certainty: our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate of the effect.

Very low certainty: we have very little confidence in the effect estimate; the true effect is likely to be substantially different from the estimate of effect.

aDowngraded twice due to imprecision cause by small participant numbers and low event rates.

Figuras y tablas -
Summary of findings 2. Bisphosphonates compared with placebo for osteoporosis in children with cystic fibrosis who have not had a lung transplant
Summary of findings 3. Bisphosphonates compared with no bisphosphonates for osteoporosis in people with cystic fibrosis who have had a lung transplant

Patient or population: adults with cystic fibrosis who have had a lung transplant

Settings: outpatients

Intervention: bisphosphonates (IV pamidronate plus oral vitamin D and oral calcium)

Comparison: oral vitamin D and oral calcium

Outcomes

Illustrative comparative risks* (95% CI)

Relative

effect

(95% CI)

Number of 

participants

(studies)

Certainty of the

evidence

(GRADE)

Comments

Assumed risk

Corresponding risk

Control

Bisphosphonates

New vertebral fractures

 

Follow‐up: 12 months

This outcome was not reported at 12 months ‐ see comments

1 study reported results at 24 months (Aris 2000) and found no difference in the number of participants with a vertebral fracture, OR 3.92 (95% CI 0.36 to 42.20)

New non‐vertebral fractures

 

Follow‐up: 12 months

This outcome was not reported at 12 months ‐ see comments

1 study reported results at 24 months (Aris 2000) and found no difference in the number of participants with a non‐vertebral fracture, OR 0.46 (95% CI 0.09 to 2.27)

BMD: % change in BMD at the lumbar spine

 

Follow‐up: 12 months

This outcome was not reported at 12 months ‐ see comments

1 study reported results at 24 months (Aris 2000) and found the % change in BMD was higher in the treatment group than the control group MD 6.20 (95% CI 4.28 to 8.12)

BMD: % change in BMD at the hip or femur

 

Follow‐up: 12 months

This outcome was not reported at 12 months ‐ see comments

1 study reported results at 24 months (Aris 2000) and found the % change in BMD was higher in the treatment group than the control group, MD 7.90 (95% CI 5.78 to 10.02).

QoL

This outcome was not reported at any time point

 

Adverse events

 

Follow‐up: 12 months

This outcome was not reported at 12 months ‐ see comment

1 study reported results at 24 months (Aris 2000) and found none of the participants in either group experienced bone pain or fever

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).

BMD: bone mineral density; CI: confidence interval; IV: intravenous; MD: mean difference; OR: odds ratio; QoL: quality of life.

GRADE Working Group grades of evidence

High certainty: we are very confident that the true effect lies close to that of the estimate of the effect.

Moderate certainty: 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 certainty: our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate of the effect.

Very low certainty: we have very little confidence in the effect estimate; the true effect is likely to be substantially different from the estimate of effect.

Figuras y tablas -
Summary of findings 3. Bisphosphonates compared with no bisphosphonates for osteoporosis in people with cystic fibrosis who have had a lung transplant
Comparison 1. Bisphosphonates versus control (without lung transplantation) ‐ adults (18 years and over)

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1.1 Total fractures Show forest plot

6

Odds Ratio (M‐H, Fixed, 95% CI)

Subtotals only

1.1.1 12 months

5

142

Odds Ratio (M‐H, Fixed, 95% CI)

0.57 [0.13, 2.50]

1.1.2 24 months

2

44

Odds Ratio (M‐H, Fixed, 95% CI)

Not estimable

1.2 Non‐vertebral fractures Show forest plot

5

Odds Ratio (M‐H, Fixed, 95% CI)

Subtotals only

1.2.1 12 months

4

95

Odds Ratio (M‐H, Fixed, 95% CI)

2.11 [0.18, 25.35]

1.2.2 24 months

2

44

Odds Ratio (M‐H, Fixed, 95% CI)

Not estimable

1.3 Vertebral fractures Show forest plot

6

Odds Ratio (M‐H, Fixed, 95% CI)

Subtotals only

1.3.1 12 months

5

142

Odds Ratio (M‐H, Fixed, 95% CI)

0.22 [0.02, 2.09]

1.3.2 24 months

2

44

Odds Ratio (M‐H, Fixed, 95% CI)

Not estimable

1.4 % change in BMD, lumbar spine [DXA] Show forest plot

8

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

1.4.1 6 months

4

101

Mean Difference (IV, Fixed, 95% CI)

4.61 [3.90, 5.32]

1.4.2 12 months

6

171

Mean Difference (IV, Fixed, 95% CI)

6.31 [5.39, 7.22]

1.4.3 24 months

2

43

Mean Difference (IV, Fixed, 95% CI)

5.49 [4.38, 6.60]

1.5 % change in BMD, lumbar spine [DXA] (end of trial data only) Show forest plot

8

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

1.5.1 End of trial

8

199

Mean Difference (IV, Fixed, 95% CI)

5.95 [5.17, 6.73]

1.6 % change in BMD, total hip/femur [DXA] Show forest plot

6

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

1.6.1 6 months

3

96

Mean Difference (IV, Fixed, 95% CI)

3.58 [2.75, 4.40]

1.6.2 12 months

5

155

Mean Difference (IV, Fixed, 95% CI)

4.41 [3.44, 5.37]

1.6.3 24 months

2

42

Mean Difference (IV, Fixed, 95% CI)

6.49 [5.32, 7.66]

1.7 % change in BMD, total hip/femur [DXA] (end of trial data only) Show forest plot

6

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

1.7.1 End of trial

6

178

Mean Difference (IV, Fixed, 95% CI)

4.89 [4.06, 5.72]

1.8 % change in BMD, distal radius [SXA] Show forest plot

2

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

1.8.1 6 months

2

48

Mean Difference (IV, Fixed, 95% CI)

0.02 [‐0.73, 0.78]

1.8.2 12 months

1

18

Mean Difference (IV, Fixed, 95% CI)

0.32 [‐0.30, 0.94]

1.8.3 24 months

1

14

Mean Difference (IV, Fixed, 95% CI)

1.50 [0.41, 2.59]

1.9 % change in BMD, distal radius [SXA] (end of trial data only) Show forest plot

2

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

1.9.1 End of study

2

42

Mean Difference (IV, Fixed, 95% CI)

0.74 [‐0.21, 1.70]

1.10 % change in BMD, ultra distal radius [SXA] Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Totals not selected

1.10.1 6 months

1

Mean Difference (IV, Fixed, 95% CI)

Totals not selected

1.11 QoL Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

1.11.1 Physical component

1

47

Mean Difference (IV, Fixed, 95% CI)

2.51 [‐1.38, 6.40]

1.11.2 Mental component

1

47

Mean Difference (IV, Fixed, 95% CI)

‐5.93 [‐11.73, ‐0.13]

1.12 Bone pain Show forest plot

7

Odds Ratio (M‐H, Fixed, 95% CI)

Subtotals only

1.12.1 All routes of bisphosphonate administration

7

206

Odds Ratio (M‐H, Fixed, 95% CI)

8.49 [3.20, 22.56]

1.12.2 Oral bisphosphonates

4

146

Odds Ratio (M‐H, Fixed, 95% CI)

4.98 [1.24, 20.09]

1.12.3 Intravenous bisphosphonates

3

60

Odds Ratio (M‐H, Fixed, 95% CI)

14.17 [3.64, 55.17]

1.13 Fever Show forest plot

5

Odds Ratio (M‐H, Fixed, 95% CI)

Subtotals only

1.13.1 All routes of bisphosphonate administration

5

118

Odds Ratio (M‐H, Fixed, 95% CI)

12.64 [2.31, 69.11]

1.13.2 Oral bisphosphonates

2

63

Odds Ratio (M‐H, Fixed, 95% CI)

Not estimable

1.13.3 Intravenous bisphosphonates

3

55

Odds Ratio (M‐H, Fixed, 95% CI)

12.64 [2.31, 69.11]

1.14 Withdrawals due to adverse events Show forest plot

6

Odds Ratio (M‐H, Fixed, 95% CI)

Subtotals only

1.14.1 6 months

2

53

Odds Ratio (M‐H, Fixed, 95% CI)

3.95 [0.14, 108.09]

1.14.2 12 months

5

177

Odds Ratio (M‐H, Fixed, 95% CI)

4.07 [1.11, 14.90]

1.14.3 24 months

2

58

Odds Ratio (M‐H, Fixed, 95% CI)

16.34 [1.98, 134.89]

1.15 Withdrawals (total) Show forest plot

6

Odds Ratio (M‐H, Fixed, 95% CI)

Subtotals only

1.15.1 6 months

2

53

Odds Ratio (M‐H, Fixed, 95% CI)

1.77 [0.27, 11.60]

1.15.2 12 months

5

177

Odds Ratio (M‐H, Fixed, 95% CI)

1.02 [0.45, 2.28]

1.15.3 24 months

2

58

Odds Ratio (M‐H, Fixed, 95% CI)

0.95 [0.34, 2.69]

1.16 Survival Show forest plot

7

Odds Ratio (M‐H, Fixed, 95% CI)

Subtotals only

1.16.1 6 months

2

36

Odds Ratio (M‐H, Fixed, 95% CI)

0.93 [0.05, 16.39]

1.16.2 12 months

4

155

Odds Ratio (M‐H, Fixed, 95% CI)

2.98 [0.30, 29.84]

1.16.3 24 months

2

58

Odds Ratio (M‐H, Fixed, 95% CI)

4.27 [0.43, 42.63]

Figuras y tablas -
Comparison 1. Bisphosphonates versus control (without lung transplantation) ‐ adults (18 years and over)
Comparison 2. Bisphosphonates versus control (without lung transplantation) ‐ children up to 18 years of age

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

2.1 Total fractures Show forest plot

1

Odds Ratio (M‐H, Fixed, 95% CI)

Totals not selected

2.1.1 12 months

1

Odds Ratio (M‐H, Fixed, 95% CI)

Totals not selected

2.2 Non‐vertebral fractures Show forest plot

1

Odds Ratio (M‐H, Fixed, 95% CI)

Totals not selected

2.2.1 12 months

1

Odds Ratio (M‐H, Fixed, 95% CI)

Totals not selected

2.3 Vertebral fractures Show forest plot

1

Odds Ratio (M‐H, Fixed, 95% CI)

Totals not selected

2.3.1 12 months

1

Odds Ratio (M‐H, Fixed, 95% CI)

Totals not selected

2.4 % change in BMD, lumbar spine, DXA Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Totals not selected

2.4.1 12 months

1

Mean Difference (IV, Fixed, 95% CI)

Totals not selected

2.5 Bone or muscle pain Show forest plot

1

Odds Ratio (M‐H, Fixed, 95% CI)

Totals not selected

2.5.1 12 months

1

Odds Ratio (M‐H, Fixed, 95% CI)

Totals not selected

2.6 Fever Show forest plot

1

Odds Ratio (M‐H, Fixed, 95% CI)

Totals not selected

2.6.1 12 months

1

Odds Ratio (M‐H, Fixed, 95% CI)

Totals not selected

2.7 Gastrointestinal adverse events Show forest plot

1

Odds Ratio (M‐H, Fixed, 95% CI)

Totals not selected

2.7.1 12 months

1

Odds Ratio (M‐H, Fixed, 95% CI)

Totals not selected

2.8 Headache Show forest plot

1

Odds Ratio (M‐H, Fixed, 95% CI)

Totals not selected

2.8.1 12 months

1

Odds Ratio (M‐H, Fixed, 95% CI)

Totals not selected

2.9 Any adverse event Show forest plot

1

Odds Ratio (M‐H, Fixed, 95% CI)

Totals not selected

2.9.1 12 months

1

Odds Ratio (M‐H, Fixed, 95% CI)

Totals not selected

2.10 Withdrawals, due to adverse events Show forest plot

1

Odds Ratio (M‐H, Fixed, 95% CI)

Totals not selected

2.10.1 12 months

1

Odds Ratio (M‐H, Fixed, 95% CI)

Totals not selected

2.11 Withdrawals, total Show forest plot

1

Odds Ratio (M‐H, Fixed, 95% CI)

Totals not selected

2.11.1 12 months

1

Odds Ratio (M‐H, Fixed, 95% CI)

Totals not selected

2.12 Survival Show forest plot

1

113

Odds Ratio (M‐H, Fixed, 95% CI)

Not estimable

2.12.1 12 months

1

113

Odds Ratio (M‐H, Fixed, 95% CI)

Not estimable

Figuras y tablas -
Comparison 2. Bisphosphonates versus control (without lung transplantation) ‐ children up to 18 years of age
Comparison 3. Bisphosphonates versus control (with lung transplantation) ‐ adults (18 years and over)

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

3.1 Total Fractures Show forest plot

1

Odds Ratio (M‐H, Fixed, 95% CI)

Totals not selected

3.1.1 24 months

1

Odds Ratio (M‐H, Fixed, 95% CI)

Totals not selected

3.2 Non‐vertebral fractures Show forest plot

1

Odds Ratio (M‐H, Fixed, 95% CI)

Totals not selected

3.2.1 24 months

1

Odds Ratio (M‐H, Fixed, 95% CI)

Totals not selected

3.3 Vertebral fractures Show forest plot

1

Odds Ratio (M‐H, Fixed, 95% CI)

Totals not selected

3.3.1 24 months

1

Odds Ratio (M‐H, Fixed, 95% CI)

Totals not selected

3.4 % change in BMD, lumbar spine, DXA Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Totals not selected

3.4.1 24 months

1

Mean Difference (IV, Fixed, 95% CI)

Totals not selected

3.5 % change in BMD, femur, DXA Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Totals not selected

3.5.1 24 months

1

Mean Difference (IV, Fixed, 95% CI)

Totals not selected

3.6 Bone pain Show forest plot

1

Odds Ratio (M‐H, Fixed, 95% CI)

Totals not selected

3.6.1 24 months

1

Odds Ratio (M‐H, Fixed, 95% CI)

Totals not selected

3.7 Withdrawals, due to adverse events Show forest plot

1

Odds Ratio (M‐H, Fixed, 95% CI)

Totals not selected

3.8 Withdrawals, total Show forest plot

1

Odds Ratio (M‐H, Fixed, 95% CI)

Totals not selected

3.8.1 24 months

1

Odds Ratio (M‐H, Fixed, 95% CI)

Totals not selected

3.9 Survival Show forest plot

1

Odds Ratio (M‐H, Fixed, 95% CI)

Totals not selected

3.9.1 24 months

1

Odds Ratio (M‐H, Fixed, 95% CI)

Totals not selected

Figuras y tablas -
Comparison 3. Bisphosphonates versus control (with lung transplantation) ‐ adults (18 years and over)