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 (CF). Bisphosphonates can increase bone mineral density (BMD) 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, BMD, quality of life, adverse events, trial withdrawals, and survival in people with CF.
Search methods
We searched the CF and Genetic Disorders Group Trials Register of references (identified from electronic database searches and handsearches of journals and abstract books) on 29 October 2008.
Additional searches of Pubmed were performed on 01 November 2008.
Selection criteria
Randomised controlled trials of at least six months duration studying bisphosphonates in people with CF.
Data collection and analysis
Two authors independently selected trials and extracted data. Trial investigators were contacted to obtain missing data.
Main results
Seven trials were identified and five (with a total of 145 adult participants) were included.
Data were combined when available from four included studies in participants without a lung transplant. This showed that there was no significant reduction in fractures between groups. However, after six months, the percentage change in BMD increased in those on bisphosphonates at the lumbar spine, mean difference (MD) 4.61 (95% confidence interval (CI) 3.90 to 5.32) and at the hip, MD 3.35 (95% CI 1.63 to 5.07); but did not significantly change at the distal forearm, MD ‐0.49 (95% CI ‐2.42‐1.45). 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, BMD increased with treatment compared to controls: percentage change in bone mineral density at lumbar spine, MD 6.20 (95% CI 4.28 to 8.12) and femur MD 7.90 (95% CI 5.78 to 10.02).
Authors' conclusions
Oral and intravenous bisphosphonates increase BMD in people with CF. 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. Trials in larger populations are needed to determine effects on fracture rate and survival.
PICOs
Plain language summary
Bisphosphonates for osteoporosis in people with cystic fibrosis
Cystic fibrosis (CF) is a serious genetic disorder that has effects on many organs (e.g. lung, pancreas). It commonly results in reduced bone mineral density (BMD), known as osteoporosis, which increases the susceptibility to fractures. The acute and chronic effects of fractures (e.g. rib and vertebral) may contribute to worsening of lung disease. Bisphosphonates are drugs that increase bone mineral density (BMD) by inhibiting bone resorption. They are used to treat osteoporosis caused by menopause or the use of corticosteroid drugs.
The evidence available was limited to four trials assessing participants without lung transplants (total of 111 adult participants) and one trial with 34 adult participants who had undergone lung transplantation. Bisphosphonates consistently increased BMD at the lumbar spine and hip regions. The rates of fractures (vertebral and non‐vertebral) or deaths were not reduced by bisphosphonate therapy. However, this may be related to the small numbers of participants involved and the short duration of the trials. Severe bone pain and flu‐like symptoms were commonly associated with intravenous bisphosphonates, especially in people not using corticosteroids. More research is needed to assess the effect of pre‐treatment with corticosteroids. 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. Trials in larger populations are needed to determine effects on fracture rate and survival.
