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Meta-Analysis
. 2014 Mar 14;2014(3):CD002010.
doi: 10.1002/14651858.CD002010.pub4.

Bisphosphonates for osteoporosis in people with cystic fibrosis

Louise S Conwell  1 , Anne B Chang
Affiliations
Meta-Analysis

Bisphosphonates for osteoporosis in people with cystic fibrosis

Louise S Conwell et al. Cochrane Database Syst Rev. .

Update in

Abstract

Background: Osteoporosis is a bone mineralisation disorder occurring in about one third of adults with cystic fibrosis. Bisphosphonates can increase bone mineral density and decrease the risk of new fractures in post-menopausal women and people receiving long-term oral corticosteroids.

Objectives: To assess the effects of bisphosphonates on the frequency of fractures, bone mineral density, quality of life, adverse events, trial withdrawals, and survival in people with cystic fibrosis.

Search methods: We searched the Cystic Fibrosis and Genetic Disorders Group Trials Register of references (identified from electronic database searches and handsearches of journals and abstract books) on 13 January 2014.Additional searches of PubMed were performed on 13 January 2014.

Selection criteria: Randomised controlled trials of at least six months duration studying bisphosphonates in people with cystic fibrosis.

Data collection and analysis: Two authors independently selected trials and extracted data. Trial investigators were contacted to obtain missing data.

Main results: Nine trials were identified and seven (with a total of 237 adult participants) were included.Data were combined (when available) from six included studies in participants without a lung transplant. Data showed that there was no significant reduction in fractures between treatment and control groups at 12 months, odds ratio 0.72 (95% confidence interval 0.13 to 3.80). No fractures were reported in studies with follow-up at 24 months. However, in patients taking bisphosphonates after six months the percentage change in bone mineral density increased at the lumbar spine, mean difference 4.61 (95% confidence interval 3.90 to 5.32) and at the hip or femur, mean difference 3.35 (95% confidence interval 1.63 to 5.07); but did not significantly change at the distal forearm, mean difference -0.49 (95% confidence interval -2.42 to 1.45). In patients taking bisphosphonates, at 12 months the percentage change in bone mineral density increased at the lumbar spine, mean difference 6.10 (95% confidence interval 5.10 to 7.10) and at the hip or femur, mean difference 4.35 (95% confidence interval 2.99 to 5.70). At 24 months, in patients treated with bisphosphonates the percentage change in bone mineral density also increased at the lumbar spine, mean difference 5.49 (95% confidence interval 4.38 to 6.60) and at the hip or femur, mean difference 6.05 (95% confidence interval 3.74 to 8.36). There was clinical heterogeneity between studies and not all studies reported all outcomes. Bone pain was the most common adverse event with intravenous agents. Flu-like symptoms were also increased in those taking bisphosphonates.In participants with a lung transplant (one study), intravenous pamidronate did not change the number of new fractures. At axial sites, bone mineral density increased with treatment compared to controls: percentage change in bone mineral density at lumbar spine, mean difference 6.20 (95% confidence interval 4.28 to 8.12); and femur mean difference 7.90 (95% confidence interval 5.78 to 10.02).

Authors' conclusions: Oral and intravenous bisphosphonates increase bone mineral density in people with cystic fibrosis. Severe bone pain and flu-like symptoms may occur with intravenous agents. Additional trials are needed to determine if bone pain is more common or severe (or both) with the more potent zoledronate and if corticosteroids ameliorate or prevent these adverse events. Additional trials are also required to further assess gastrointestinal adverse effects associated with oral bisphosphonates. Trials in larger populations are needed to determine effects on fracture rate and survival.

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Conflict of interest statement

None known.

Figures

1.1
1.1. Analysis
Comparison 1 Bisphosphonates versus control (without lung transplantation), Outcome 1 Vertebral fractures.
1.2
1.2. Analysis
Comparison 1 Bisphosphonates versus control (without lung transplantation), Outcome 2 Non‐vertebral fractures.
1.3
1.3. Analysis
Comparison 1 Bisphosphonates versus control (without lung transplantation), Outcome 3 Total Fractures.
1.4
1.4. Analysis
Comparison 1 Bisphosphonates versus control (without lung transplantation), Outcome 4 Per cent change in BMD, lumbar spine, DXA (Time‐points).
1.5
1.5. Analysis
Comparison 1 Bisphosphonates versus control (without lung transplantation), Outcome 5 Per cent change in BMD, lumbar spine, DXA (End of study).
1.6
1.6. Analysis
Comparison 1 Bisphosphonates versus control (without lung transplantation), Outcome 6 Per cent change in BMD, total hip / femur, DXA (Time‐points).
1.7
1.7. Analysis
Comparison 1 Bisphosphonates versus control (without lung transplantation), Outcome 7 Per cent change in BMD, total hip/femur, DXA (End of study).
1.8
1.8. Analysis
Comparison 1 Bisphosphonates versus control (without lung transplantation), Outcome 8 Per cent change in BMD, distal radius, SXA (Time‐points).
1.9
1.9. Analysis
Comparison 1 Bisphosphonates versus control (without lung transplantation), Outcome 9 Per cent change in BMD, distal radius, SXA (End of study).
1.10
1.10. Analysis
Comparison 1 Bisphosphonates versus control (without lung transplantation), Outcome 10 Per cent change in BMD, ultra distal radius, SXA.
1.11
1.11. Analysis
Comparison 1 Bisphosphonates versus control (without lung transplantation), Outcome 11 Quality of Life.
1.12
1.12. Analysis
Comparison 1 Bisphosphonates versus control (without lung transplantation), Outcome 12 Bone pain.
1.13
1.13. Analysis
Comparison 1 Bisphosphonates versus control (without lung transplantation), Outcome 13 Fever.
1.14
1.14. Analysis
Comparison 1 Bisphosphonates versus control (without lung transplantation), Outcome 14 Withdrawals, due to adverse events.
1.15
1.15. Analysis
Comparison 1 Bisphosphonates versus control (without lung transplantation), Outcome 15 Withdrawals, total.
1.16
1.16. Analysis
Comparison 1 Bisphosphonates versus control (without lung transplantation), Outcome 16 Survival.
2.1
2.1. Analysis
Comparison 2 Bisphosphonates versus control (with lung transplantation), Outcome 1 Vertebral fractures.
2.2
2.2. Analysis
Comparison 2 Bisphosphonates versus control (with lung transplantation), Outcome 2 Non‐vertebral fractures.
2.3
2.3. Analysis
Comparison 2 Bisphosphonates versus control (with lung transplantation), Outcome 3 Total Fractures.
2.4
2.4. Analysis
Comparison 2 Bisphosphonates versus control (with lung transplantation), Outcome 4 Per cent change in BMD, lumbar spine, DXA.
2.5
2.5. Analysis
Comparison 2 Bisphosphonates versus control (with lung transplantation), Outcome 5 Per cent change in BMD, femur, DXA.
2.6
2.6. Analysis
Comparison 2 Bisphosphonates versus control (with lung transplantation), Outcome 6 Bone pain.
2.7
2.7. Analysis
Comparison 2 Bisphosphonates versus control (with lung transplantation), Outcome 7 Withdrawals, due to adverse events.
2.8
2.8. Analysis
Comparison 2 Bisphosphonates versus control (with lung transplantation), Outcome 8 Withdrawals, total.
2.9
2.9. Analysis
Comparison 2 Bisphosphonates versus control (with lung transplantation), Outcome 9 Survival.
See this image and copyright information in PMC

Update of

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