Fracture Incidence in Polyostotic Fibrous Dysplasia and the McCune-Albright Syndrome

Authors

  • Arabella I Leet,

    1. Craniofacial and Skeletal Diseases Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA
    2. Department of Orthopedics, Division of Pediatric Orthopedics, Johns Hopkins University, Baltimore, Maryland, USA
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  • Caroline Chebli,

    1. Craniofacial and Skeletal Diseases Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA
    2. Department of Orthopaedic Surgery, University of Maryland, Baltimore, Maryland, USA
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  • Harvey Kushner,

    1. Biomedical Computer Research Institute, Philadelphia, Pennsylvania, USA
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  • Clara C Chen,

    1. Department of Nuclear Medicine, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA
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  • Marilyn H Kelly,

    1. Nursing Services of the Warren Grant Magnuson Clinical Center, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA
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  • Beth A Brillante,

    1. Nursing Services of the Warren Grant Magnuson Clinical Center, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA
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  • Pamela G Robey,

    1. Craniofacial and Skeletal Diseases Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA
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  • Paolo Bianco,

    1. Craniofacial and Skeletal Diseases Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA
    2. Dipartimento di Medicina Sperimentale e Patologia, Unversita “La Sapienza,” Rome, Italy
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  • Shlomo Wientroub,

    1. Craniofacial and Skeletal Diseases Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA
    2. Department of Pediatric Orthopaedic Surgery, Dana Children's Hospital, Tel-Aviv Medical Center, Tel-Aviv University, Tel-Aviv, Israel
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  • Michael T Collins

    Corresponding author
    1. Craniofacial and Skeletal Diseases Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA
    • CSDB/NIDCR/National Institutes of Health, Building 30, Room 228, MSC 4320, Bethesda, MD 20892–4320, USA
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  • The authors have no conflict of interest.

Abstract

In patients with polyostotic fibrous dysplasia of bone, the peak incidence of fractures is during the first decade of life, followed by a decrease thereafter. Phosphaturia is associated with an earlier incidence and increased frequency of fractures.

Introduction: Fibrous dysplasia (FD) is a disorder involving either one (monostotic) or several bones (polyostotic FD [PFD] and sometimes is associated with cafe-au-lait hyperpigmentation of the skin and one or more hyperfunctioning endocrinopathies (McCune-Albright syndrome [MAS]). Both PFD and MAS are often associated with phosphaturia. Although fractures occur frequently in PFD/MAS, fracture incidence and the effect of age and co-existing metabolic abnormalities (endocrinopathy and/or phosphaturia) on fractures are ill defined.

Materials and Methods: We reviewed the medical records and examined the endocrine and phosphorus metabolism of 35 patients with PFD/MAS. We report on the age at which extremity fractures occurred and their location and treatment. The results of endocrine and phosphorus metabolism testing and associations between age of first fractures, number of fractures, fracture rate, and metabolic abnormalities were noted.

Results: The average follow-up was 14.2 years (range, 2–39 years), during which 172 fractures occurred. The number and sites of fractures were 103 femoral, 25 tibial, 33 humeral, and 11 forearm. Twenty-seven patients had PFD with one or more endocrinopathies and/or phosphaturia, and eight had PFD alone. The endocrinopathies included precocious puberty (n = 19), hyperthyroidism (n = 9), growth hormone excess (n = 6), and one patient each with Cushing syndrome and primary hyperparathyroidism. Twelve patients had phosphaturia. The peak rate of fractures occurred between 6 and 10 years of age and decreased thereafter. Patients with metabolic abnormalities sustained their first fracture at an earlier age (6.9 versus 16.6 years, p < 0.005) and had a higher lifetime rate of fractures (0.29 versus 0.08 fractures/year), relative to patients with PFD alone. Phosphaturia was the single metabolic dysfunction associated with both an earlier age of first fracture (5.1 versus 16.6 years, p < 0.05) and a greater lifetime fracture rate (0.35 versus 0.08 fractures/year, p < 0.05).

Conclusions: The occurrence of extremity fractures in FD peaks between 6 and 10 years of age and declines thereafter. Fractures occur earlier and more frequently in the presence of phosphaturia. These data have implications for long-term prognosis, clinical management, and interpretation of therapeutic interventions.

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