Bisphosphonates for osteoporosis in people with cystic fibrosis.
BACKGROUND
Osteoporosis is a disorder of bone mineralization that can lead to reduced bone mineral density and an increased risk for fractures. It is found in about one third of adults with cystic fibrosis. Bisphosphonates have been shown to increase bone mineral density and decrease the risk of new fractures in post-menopausal women and in patients receiving long-term oral corticosteroids.


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


METHODS
Relevant trials were identified in the Cochrane Cystic Fibrosis and Genetic Disorders Review Group specialised register of controlled trials by the centre co-ordinator. This register comprises references identified from comprehensive electronic database searches, handsearching of relevant journals and of conference proceedings. Additional sources such as abstract books for osteoporosis conferences were hand-searched by the authors. The most recent search(es) were conducted in February 2001.


METHODS
Randomised controlled trials of at least six months duration that studied the use of bisphosphonates in adults with cystic fibrosis were considered for inclusion. Outcomes included one of the following: fractures, bone mineral density, quality of life, adverse events, study withdrawals, or survival.


METHODS
Information on study design, participants, interventions, and outcomes was abstracted from included studies. Two independent reviewers abstracted the information. Authors were contacted to obtain missing data.


RESULTS
Two trials were identified in the trials search. Both trials with a total of 65 participants were included in this review. One study examined patients without lung transplants while the other study included only patients who had received a lung transplant. The intervention in both trials was pamidronate administered intravenously every three months. In patients who had not received a lung transplant, bone mineral density at axial sites was increased after six months of treatment in the treatment group compared to the control group (lumbar spine WMD [for % change BMD] = 5.8 [95% CI 4.63 to 6.97], hip WMD = 3.00 [95% CI 1.99 to 4.01]). There was a small decrease in forearm bone mineral density in patients treated with pamidronate versus controls (distal forearm WMD = -1.70 [95% CI -2.46 to -0.94]). Bone pain was the most common adverse event occurring in 11/15 participants not using corticosteroids (RR = 24.40, 95% CI 1.57 to 381.48). There was no difference in survival (RR = 1.00, 95% CI 0.83 to 1.20), although this may be due to short follow-up and small sample size. In patients who had received a lung transplant, the number of new fractures did not change with the use of pamidronate (non-vertebral RR = 3.38 [95% CI 0.39 to 29.29], vertebral RR = 0.56 [95% CI 0.17 to 1.89]). Bone mineral density at axial sites was increased after two years of treatment in the treatment group compared to the control group (lumbar spine WMD [for % change in BMD] = 6.20 [95% CI 4.28 to 8.12], femur WMD = 7.90 [95% CI 5.78 to 10.03]).


CONCLUSIONS
Intravenous pamidronate increases bone mineral density at axial sites in people with cystic fibrosis, although it can cause severe bone pain in patients not receiving corticosteroids. Additional studies in larger populations are needed to determine the effect on fracture rate and survival.
Brenckmann
C
C
Community Health and Epidemiology, Dalhousie University, 5849 University Avenue, Halifax, Nova Scotia, Canada, B3H 4H7. cbrenckmann@hotmail.com
Papaioannou
A
A
D015519:Bone Density / Q000187:drug effects; D003550:Cystic Fibrosis / Q000150:complications*; D004164:Diphosphonates / Q000627:therapeutic use*; D050723:Fractures, Bone / Q000517:prevention & control; D006801:Humans; D016040:Lung Transplantation; D010024:Osteoporosis / Q000188:drug therapy*; D016032:Randomized Controlled Trials as Topic
D004164:Diphosphonates