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Management of Osteoporosis in Adults with Cystic Fibrosis

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Abstract

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.

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Acknowledgements

The authors would like to thank the attendees of the 2002 June 11–12 Cystic Fibrosis Foundation consensus conference on bone health and disease for their input. Additionally, the authors would like to thank SA Brown and DA Ontjes for their guidance and suggestions for this manuscript. We received grant support from the Cystic Fibrosis Foundation (ARIS00A0), the US FDA (FD-R-001518-01), the Clinical Nutrition Research Unit (NIH DK 56350), Merck and Co., Inc. (Medical School Grants Program) and the Verne S. Caviness General Center for Clinical Research at the University of North Carolina at Chapel Hill.

R.M. Aris received a grant of $US30 000 from the Merck Medical School Grants Program to provide seed money for an investigator-initiated, US FDA-sponsored study of alendronate versus placebo in adults with cystic fibrosis that resulted in the study cited in section 3.[67]

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  1. Division of Pulmonary and Critical Care Medicine, The University of North Carolina at Chapel Hill, CB# 7020, 4131 Bioinformatics Bldg, Chapel Hill, North Carolina, 27599-7524, USA

    Travis M. Hecker &  Robert M. Aris

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Hecker, T.M., Aris, R.M. Management of Osteoporosis in Adults with Cystic Fibrosis. Drugs 64, 133–147 (2004). https://doi.org/10.2165/00003495-200464020-00002

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