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Relationship between insulin-like growth factor I, dehydroepiandrosterone sulfate and proresorptive cytokines and bone density in cystic fibrosis

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Abstract

Introduction

Patients with cystic fibrosis (CF) are known to be at risk for early osteoporosis, and the mechanisms that mediate bone loss are still being delineated. The aim of the present investigation was to investigate if a correlation exists in these patients between skeletal measurements by dual-energy x-ray absorptiometry (DXA) and two anabolic factors, dehydroepiandrosterone (DHEA) and insulin-like growth factor I (IGF-I), and proresorptive factors such as the cytokines interleukin-1β, tumor necrosis factor α, and interleukin-6.

Methods

We studied 32 outpatients (18 females; mean age: 26.2 ± 7.9 years) at a tertiary care medical center. The subjects had venous samples obtained, underwent anthropometric and bone mineral density (BMD) measurements, and completed a health survey. Serum IGF-I concentrations were below the age-adjusted mean in 78% of the participants, and DHEA sulfate (DHEAS) concentrations were low in 72%. Serum concentrations of all cytokines were on the low side of normal; nonetheless, there was a modest inverse correlation between IL-1β and BMD at all sites.

Results

In univariate analyses, IGF-I and DHEAS were significant correlates of BMD or bone mineral content. In final multivariate models controlling for anthropometric and other variables of relevance to bone density, only IGF-I was identified as a significant independent skeletal predictor. While alterations in DHEAS, IGF-I, and specific cytokines may contribute to skeletal deficits in patients with CF, of these factors a low IGF-I concentration appears to be most strongly correlated with BMD.

Conclusions

These findings may have therapeutic implications for enhancing bone density in these patients.

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Acknowledgements

We wish to thank our patients for their participation, and the skilled and dedicated nurses in the General Clinical Research Center for their excellent patient care. We also gratefully acknowledge Suzanne Muggeo, BA and Julie Burgess, BS, for technical support, Avery LeBoff Williams for editorial assistance, and Henry A. Feldman, PhD for biostatistical advice. This work was funded by NIH Grant MO1-RR-2172 and Project 5-T71-MC-0000-10-S1-RO from the Maternal and Child Health Bureau.

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Authors and Affiliations

  1. Children’s Hospital, Boston, MA, USA

    C. M. Gordon, E. Binello, M. E. Wohl & A. A. Colin

  2. Brigham and Women’s Hospital, Boston, MA, USA

    M. S. LeBoff

  3. St. Joseph Hospital, Bangor, ME, USA

    C. J. Rosen

  4. Children’s Hospital, Division of Endocrinology, 300 Longwood Avenue, Boston, MA, 02115, USA

    C. M. Gordon

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  1. C. M. Gordon
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  2. E. Binello
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  3. M. S. LeBoff
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  6. A. A. Colin
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Correspondence to C. M. Gordon.

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Gordon, C.M., Binello, E., LeBoff, M.S. et al. Relationship between insulin-like growth factor I, dehydroepiandrosterone sulfate and proresorptive cytokines and bone density in cystic fibrosis. Osteoporos Int 17, 783–790 (2006). https://doi.org/10.1007/s00198-005-0058-x

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