Cystic Fibrosis: Bisphosphonate Ups Bone Density in Children

Ricki Lewis, PhD

June 06, 2013

As life expectancy increases for people who have cystic fibrosis (CF), risk for osteoporosis and fragility fractures increases. Bisphosphonates may counter the loss of bone mineral density (BMD) if begun in childhood, according to results from a study published online June 2 in the Lancet.

Maria Luisa Bianchi, MD, from Istituto Auxologico Italiano, Istituto Di Ricovero e Cura a Carattere Scientifico, Milan, Italy, and colleagues conducted a multicenter, prospective, open-label observational study of the effect of calcium and vitamin D on BMD in young people with CF, followed by a randomized, placebo-controlled trial of the bisphosphonate drug alendronate. The drug is recommended for adults with CF and low BMD but has not been tested in children or adolescents.

The exact cause of osteoporosis and fragility fractures in people with CF is unknown, but contributing factors include years of calcium and vitamin D deficiencies resulting from malnutrition and malabsorption, little physical activity, respiratory failure, liver disease, deficiencies of vitamins D and K, systemic inflammation, delayed puberty, low levels of insulin-like growth factor 1, glucocorticosteroid treatments, and chronic lung infections. Fractures are dangerous in this population because they further limit exercise, increase the risk for lung infection, and make daily respiratory physiotherapy difficult or impossible.

In the first part of the study, the investigators monitored calcium and vitamin D intake after nutritional counseling among 171 patients with CF who had a low BMD and ranged in age from 5 to 30 years. Participants whose BMD had not improved more than 5% within a year (75%) joined the second part of the study, in which 128 patients were assigned daily oral alendronate or placebo for a year.

The researchers assessed lumbar spine BMD, using dual X-ray absorptiometry at baseline and every 6 months, and blood and urine markers every 3 to 6 months. Increase in lumbar BMD was the primary endpoint.

The results were striking: BMD increased 16.3% among the 65 patients who received the bisphosphonate and only 3.1% among the 63 patients who received placebo. A third of the treated patients attained a BMD that was normal for their ages. The number of adverse effects was the same in each group.

The researchers conclude that alendronate safely and efficaciously improves bone mineral density in young people with CF in whom dietary calcium and vitamin D are insufficient.

Limitations of the study include the limited time frame and the inability to assess effect on fracture risk because of the small sample.

In an accompanying comment, Carole Le Henaff, PhD, from the University Reims Champagne Ardenne in France, and colleagues state that the researchers "provide convincing evidence that the oral bisphosphonate alendronate is effective, well tolerated, and safe for young patients with cystic fibrosis." They also note that the drug did not completely suppress bone formation in children but did so in the young adults, which they suggest could reflect alendronate's enhancing the effects of reaching sexual maturity on bone formation. Dr. Le Henaff and colleagues also suggest investigation of effects of new CF drugs (such as Kalydeco, Vertex Pharmaceuticals) on BMD.

This project was supported by the Telethon Foundation, and Abiogen SpA supplied placebo at no cost. The researchers and commentators have disclosed no relevant financial relationships.

Lancet. Published online June 2, 2013. Abstract

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