Bisphosphonates for osteoporosis in people with cystic fibrosis

Louise Conwell, Anne Chang

Research output: Contribution to journalArticleResearchpeer-review

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.

Original languageEnglish
Article numberCD002010
Pages (from-to)1-40
Number of pages40
JournalCochrane Database of Systematic Reviews
Volume2014
Issue number3
DOIs
Publication statusPublished - 13 Mar 2014

Fingerprint

Diphosphonates
Cystic Fibrosis
Osteoporosis
Bone Density
Confidence Intervals
Femur
Spine
Hip
pamidronate
zoledronic acid
Bone and Bones
Pain
Adrenal Cortex Hormones
Transplants
Physiologic Calcification
Lung
Fracture Fixation
Inborn Genetic Diseases
PubMed
Forearm

Cite this

@article{2dd97b18a19340238275ac8101f2176a,
title = "Bisphosphonates for osteoporosis in people with cystic fibrosis",
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.",
author = "Louise Conwell and Anne Chang",
year = "2014",
month = "3",
day = "13",
doi = "10.1002/14651858.CD002010.pub4",
language = "English",
volume = "2014",
pages = "1--40",
journal = "Cochrane database of systematic reviews (Online)",
issn = "1469-493X",
publisher = "John Wiley & Sons",
number = "3",

}

Bisphosphonates for osteoporosis in people with cystic fibrosis. / Conwell, Louise; Chang, Anne.

In: Cochrane Database of Systematic Reviews, Vol. 2014, No. 3, CD002010, 13.03.2014, p. 1-40.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Bisphosphonates for osteoporosis in people with cystic fibrosis

AU - Conwell, Louise

AU - Chang, Anne

PY - 2014/3/13

Y1 - 2014/3/13

N2 - 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.

AB - 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.

U2 - 10.1002/14651858.CD002010.pub4

DO - 10.1002/14651858.CD002010.pub4

M3 - Article

VL - 2014

SP - 1

EP - 40

JO - Cochrane database of systematic reviews (Online)

JF - Cochrane database of systematic reviews (Online)

SN - 1469-493X

IS - 3

M1 - CD002010

ER -