The first randomised trial to investigate the treatment of low bone density in young people with cystic fibrosis (CF), published Online First in The Lancet Respiratory Medicine, provides compelling evidence that alendronate (a drug that curbs bone loss) is safe and can help increase bone mineral density (BMD) in young patients with CF after standard treatment with calcium and vitamin D has failed.
Improvements in treatments have increased the life expectancy of people with CF to about 40 years, putting them at high risk of long-term complications such as osteoporosis and bone fractures.
Current treatments in younger CF patients like calcium and vitamin D aren’t always enough to maintain BMD. Although treatment with bisphosphonates is recommended in adults with CF, until now, they have not been tested in clinical trials of children and adolescents.
In the first part of this large Italian multicenter trial, 171 young people (aged 5-30 years) with CF and low BMD received counselling to increase their dietary calcium intake to the daily recommended allowance plus a daily dose of vitamin D (calcifediol).
Maria Luisa Bianchi from Istituto Auxologico Italiano IRCCS in Milan and colleagues measured changes in BMD of the lumbar spine using dual energy x-ray absorptiometry and changes in serum and urine bone markers at the beginning of the study and every 3-6 months.
After 12 months of calcium and calcifediol, BMD had increased by 5% or more (the minimum annual increase expected for patients of this age range) in just a quarter of patients (43).
In the second part of the trial, the 128 patients not responding to calcium plus calcifediol treatment after one year were randomly assigned to a daily dose of oral alendronate or placebo for an additional 12 months.
Between 12 and 24 months, BMD increased by 16.3% in those taking alendronate compared to 3.1% in those given placebo. Importantly, a third of young people attained a normal-for-age Z-score* after only 12 months of alendronate treatment.
According to Bianchi, “Bisphosphonates can be prudently used in young patients, when other and simpler measures (eg, calcium and vitamin D) have failed… Further research is needed to assess the effects of bisphosphonates on fracture risk.”
Writing in a linked Comment Jacky Jacquot and colleagues from the French National Institute of Health and Medical Research (Inserm) say, “The prevalence of osteopenia in young patients with cystic fibrosis–as confirmed by Bianchi and colleagues– suggests that bone mineral density should be carefully assessed in children and adolescents with cystic fibrosis, especially those with associated risk factors, to avoid the most common clinical sequelae of osteoporosis: vertebral compression fracture…Early recognition and treatment are the most effective strategies for sustaining bone health to help maintain quality of life in young patients with cystic fibrosis. Few clinical trials have included children: such trials are needed to assess the effect of bisphosphonates on long-term outcomes.”
* A measured BMD value to the average value obtained from a healthy population of the same sex and age as the patient.
“Treatment of low bone density in young people with cystic fibrosis: a multicentre, prospective, open-label observational study of calcium and calcifediol followed by a randomised placebo-controlled trial of alendronate”,
Maria Luisa Bianchi et al.
The Lancet Respiratory Medicine June 2, 2013 http://dx.doi.org/10.1016/S2213-2600(13)70064-X