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Bone Density and Fractures in Autosomal Dominant Hyper IgE Syndrome

Journal of Clinical Immunology volume 34, pages 260–264 (2014)Cite this article

Abstract

Purpose

Autosomal Dominant Hyper IgE Recurrent Infection Syndrome (AD-HIES) is caused by mutations in STAT3 and characterized by eczema, recurrent bacterial infections, and skeletal and connective tissue abnormalities. To further understand the minimal trauma fractures of AD-HIES, we examined bone mineral density (BMD) and laboratory markers of bone turnover.

Methods

Patients with AD-HIES enrolled in a prospective natural history study were examined with dual x-ray absorptiometry (DEXA) scans and laboratory studies of bone metabolism. The number of fractures was recorded as well as clinical features of AD-HIES including scoliosis and retained primary teeth. Patients on medications with skeletal effects, including bisphosphonates, were examined separately.

Results

Twenty-three AD-HIES children (6–18 years) and 33 AD-HIES adults (21–50 years) not receiving bone-active drugs were studied. Fourteen of the 23 children (61 %) had histories of minimal trauma fractures, as did 26 of the 33 adults (79 %). Osteopenia or osteoporosis was found in 79 % of children and adults. Only radial BMD correlated with the qualitative occurrence of fractures but it did not correlate with the numbers of fractures. Markers of bone metabolism did not correlate with minimal trauma fractures or BMD. Patients on bone-active medications had improved BMD, but still sustained fractures.

Conclusions

Minimal trauma fractures and decreased BMD are common in AD-HIES. Low radial BMD is associated with fractures, but hip and spine BMD are not. Treatment with bisphosphonates increased BMD but its role in fracture prevention remains undefined.

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Publication disclaimer

This research was supported by the Division of Intramural Research, NIAID, NIH. The views expressed in this article are those of the authors and do not reflect the official policy of the U.S. Government. This project has been funded in part with federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. government. This research was supported [in part] by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health.

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Affiliations

  1. Laboratories of Clinical Infectious Diseases, NIAID, NIH, Bethesda, MD, USA

    Kathryn J. Sowerwine, Dirk N. Darnell, Victoria L. Anderson, Joie Davis, Amy Hsu, Steven M. Holland & Alexandra F. Freeman

  2. Biostatistics Research Branch, National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA

    Pamela A. Shaw

  3. Biostatistics Research Branch, Clinical Research Directorate/CMRP SAIC-Frederick, National Laboratory for Cancer Research, Frederick, MD, 21703, USA

    Wenjuan Gu & Pamela Welch

  4. Department of Allergy and Infectious Diseases, University of Washington, Seattle, WA, USA

    Jennifer C. Ling

  5. Skeletal Clinical Studies Unit, Craniofacial and Skeletal Diseases Branch, NIDCR, NIH, Bethesda, MD, USA

    Michael T. Collins

  6. Department of Pediatrics, University of California San Francisco, San Francisco, CA, USA

    Jennifer M. Puck

Authors
  1. Kathryn J. Sowerwine
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  2. Pamela A. Shaw
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  3. Wenjuan Gu
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  4. Jennifer C. Ling
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  5. Michael T. Collins
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  6. Dirk N. Darnell
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  7. Victoria L. Anderson
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  8. Joie Davis
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  9. Amy Hsu
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  10. Pamela Welch
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  11. Jennifer M. Puck
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  12. Steven M. Holland
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  13. Alexandra F. Freeman
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Corresponding author

Correspondence to Alexandra F. Freeman.

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Sowerwine, K.J., Shaw, P.A., Gu, W. et al. Bone Density and Fractures in Autosomal Dominant Hyper IgE Syndrome. J Clin Immunol 34, 260–264 (2014). https://doi.org/10.1007/s10875-013-9982-2

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  • DOI: https://doi.org/10.1007/s10875-013-9982-2

Keywords

  • Autosomal dominant hyper IgE syndrome (AD-HIES)
  • job’s syndrome
  • signal transducer and activator of transcription 3 (STAT3)
  • osteoporosis
  • retained primary teeth