Renal Phosphate Wasting in Fibrous Dysplasia of Bone Is Part of a Generalized Renal Tubular Dysfunction Similar to That Seen in Tumor-Induced Osteomalacia

Authors

  • Michael T. Collins,

    Corresponding author
    1. Craniofacial and Skeletal Diseases Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland, USA
    • Address reprint requests to: Michael T. Collins, Craniofacial and Skeletal Diseases Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Building 30, Room 228, MSC 4320, Bethesda, MD 20892-4320, USA
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  • Caroline Chebli,

    1. Department of Orthopedic Surgery, Westchester Medical Center, Valhala, New York, USA
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  • Janet Jones,

    1. Arthritis Research Branch, National Institute of Arthritis Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland, USA
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  • Harvey Kushner,

    1. Biomedical Computer Research Institute, Philadelphia, Pennsylvania, USA
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  • Mark Consugar,

    1. Biochemical Genetics Laboratory, Department of Laboratory Medicine and Pathology, Mayo Clinic Foundation, Rochester, Minnesota, USA
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  • Piero Rinaldo,

    1. Biochemical Genetics Laboratory, Department of Laboratory Medicine and Pathology, Mayo Clinic Foundation, Rochester, Minnesota, USA
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  • Shlomo Wientroub,

    1. Department of Pediatric Orthopedic Surgery, Dana Children's Hospital, Tel-Aviv Medical Center, Tel-Aviv, Israel
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  • Paolo Bianco,

    1. Division of Pathology, Department of Experimental Medicine, University of Rome ‘La Sapienza,’ Rome, Italy
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  • Pamela Gehron Robey

    1. Craniofacial and Skeletal Diseases Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland, USA
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Abstract

Fibrous dysplasia (FD) of bone is characterized by focal replacement of normal bone and marrow with abnormal bone and fibrous tissue. It arises from postzygotic activating mutations of the GNAS1 gene. Hypophosphatemia due to renal phosphate wasting has been reported in association with FD as a part of the McCune-Albright Syndrome (MAS), which is characterized by FD, skin hyperpigmentation, and precocious puberty. To date, the prevalence and mechanism of phosphate wasting has not been well studied. We evaluated 42 patients with FD/MAS. Serum and urine samples were tested for indices of mineral metabolism, amino acid handling, and markers of bone metabolism. Twenty (48%) patients had some degree of renal phosphate wasting. Nephrogenous cyclic adenosine monophosphate (cAMP) was normal in FD patients, suggesting that the underlying cause of phosphate wasting is not the presence of activating GNAS1 mutations in the kidney. In addition, there was evidence of a more generalized renal tubulopathy as represented by the presence of abnormal vitamin D metabolism, proteinuria in 36 (86%) patients, and aminoaciduria in 39 (94%) patients. Renal phosphate wasting significantly correlated with the degree of bone involvement, as assessed by serum and urine markers of bone metabolism, suggesting that a circulating factor produced by FD bone and impacting on the kidney may be the mechanism. These data show that phosphaturia as part of a generalized renal tubulopathy represents the most common extraskeletal manifestation of FD and that the observed tubulopathy is similar to that seen in tumor-induced osteomalacia (TIO).

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