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 strategy: 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.