Renal phosphate wasting in fibrous dysplasia of bone is part of a generalized renal tubular dysfunction similar to that seen in tumor-induced osteomalacia

Fibrous dysplasia (FD) of bone is characterized by focal replacement of nor mal bone and marrow with abnormal bone and fibrous tissue. It arises from p ostzygotic 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 h yperpigmentation, and precocious puberty. To date, the prevalence and mecha nism of phosphate wasting has not been well studied. We evaluated 42 patien ts 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 g eneralized renal tubulopathy as represented by the presence of abnormal vit amin D metabolism, proteinuria in 36 (86%) patients, and aminoaciduria in 3 9 (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 i mpacting on the kidney may be the mechanism, These data show that phosphatu ria as part of a generalized renal tubulopathy represents the most common e xtraskeletal manifestation of FD and that the observed tubulopathy is simil ar to that seen in tumor-induced osteomalacia (TIO).