Management of osteoporosis in adults with cystic fibrosis.

Cystic fibrosis (CF) is the most common genetic disease that causes respiratory failure within the Caucasian population. The life span of patients with CF has gradually increased from a median of 2 years of age to >30 years. Concurrent with this increased lifespan, a variety of other nutritional, endocrine and bone issues have been recognised. Decreased absorption of fat-soluble vitamins (D and K in particular) because of pancreatic insufficiency, altered sex hormone production, chronic inflammation, a lack of physical activity, glucocorticoid treatment and an intrinsic hyper-resorptive bone physiology are some of the factors that contribute to the prominence of bone disease within the CF population. In some series, three-quarters of adult patients with CF have osteopenia or osteoporosis. Lung transplantation is one viable treatment for patients with end-stage CF, which requires a lifetime of antirejection medication. Immunosuppressant therapies have a detrimental effect on bone mineral density (BMD). To combat the multifactorial nature of CF-related bone disease, advances in nutritional and vitamin supplementation, and anti-resorptive and anabolic therapies have evolved. Chronic vitamin D depletion contributes to bone disease in the CF population. The isoform of vitamin D that is the best and safest supplement, with the lowest cost, has yet to be identified. However, it is clear that many patients with CF who receive the standard of care (i.e. two daily combination vitamin A, D, E and K tablets [ADEKs]) may still be vitamin D-deficient. More aggressive supplementation needs to be individualised, with close monitoring of serum 25-hydroxyvitamin D levels. Similarly, routine calcium supplementation may be important, and evidence is accumulating that vitamin K also plays an important role in maximising and maintaining BMD. Early recognition and treatment of delayed puberty in adolescents and hypogonadism in adults with hormone replacement therapy is recommended to maintain BMD in patients with CF. Bisphosphonates, including pamidronic acid, etidronic acid and alendronic acid, reduce bone resorption by inhibiting the recruitment and function of osteoclasts. Pamidronic acid is beneficial in improving BMD in CF patients before and after transplantation. Bisphosphonate therapy and minimisation of glucocorticoid dosage have been shown to be efficacious in glucocorticoid-induced osteoporosis. Teriparatide is the first US FDA-approved anabolic growth agent for bone, and has been shown to increase BMD and decrease fracture incidence in postmenopausal women. Teriparatide may offer a new avenue for treating bone disease in CF since many patients may have poor bone formation as well as accelerated bone breakdown. Numerous clinical trials are underway to optimise treatment of CF osteoporosis.

Efficacy of alendronate in adults with cystic fibrosis with low bone density.

As adults with cystic fibrosis (CF) have enjoyed incremental increases in longevity over the last few decades, they have also been suffering from low bone density and its clinical manifestations, fractures and kyphosis. We conducted a placebo-controlled, randomized, double-blinded trial of alendronate (10 mg/day orally) (n = 24) compared with placebo (n = 24) for 1 year in 48 patients to improve bone mineral density at the spine as the primary endpoint. All patients received 800 IU of cholecalciferol and 1,000 mg of calcium carbonate. Both groups were similar in age, sex, CF mutations, bone density T scores, renal function, and body mass index at study onset. The alendronate-treated patients gained (mean +/- SD) 4.9 +/- 3.0% and 2.8 +/- 3.2% bone density after 1 year versus placebo, which lost (mean +/- SD) 1.8 +/- 4.0% and 0.7 +/- 4.7%, in spine and femur bone density, respectively (p < or = 0.001 for the spine; p = 0.003 for the femur). Urine N-telopeptide, a bone resorption marker, levels declined in the treatment group more than in the control group (p = 0.002), consistent with the known antiresorptive effects of bisphosphonates. Alendronate was more effective than placebo in improving spine and femur bone mineral density and is a promising agent for the long-term prevention and management of bone disease in patients with CF.