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Fibroblast Growth Factor 23: A New Clinical Marker for Oncogenic Osteomalacia

Cancer Genetics, Kolling Institute of Medical Research, University of Sydney and Royal North Shore Hospital (A.E.N., R.C.B., M.M., A.A., B.G.R.), and Endocrinology Department (R.C.B., B.G.R., P.C.B.), Department of Surgery (S.R.), and Anatomical Pathology Department, PaLMS (A.G., A.C.), Royal North Shore Hospital, St. Leonards, Sydney 2065, Australia; Physiology Department, Institute of Biomedical Research, University of Sydney (A.E.N., M.M., A.A., R.S.M.), Sydney 2006, Australia; Endocrine Unit, Departments of Medicine and Pediatrics, Massachusetts General Hospital and Harvard Medical School (H.J.), Boston, Massachusetts 02114; and Department of Surgery (P.S.) and Anatomical Pathology Department (R.A.S.), Royal Prince Alfred Hospital, Sydney 2050, Australia

Address all correspondence and requests for reprints to: Dr. Anne E. Nelson, Cancer Genetics Department, Kolling Institute of Medical Research, Royal North Shore Hospital, St. Leonards, Sydney 2065, Australia. E-mail: annen{at}med.usyd.edu.au.

The phosphate-wasting condition, oncogenic osteomalacia, is problematic to diagnose and manage clinically due to difficulty in locating the causative tumor. Fibroblast growth factor 23 (FGF23) has recently been implicated in the pathogenesis of oncogenic osteomalacia. In this case the patient presented with clinical features typical of oncogenic osteomalacia. Removal of an angiolipoma from the thigh did not correct the clinical or biochemical abnormalities. Subsequent identification and removal of a benign giant cell tumor in the pubic ramus, however, did result in normalization of his symptoms and signs. Positive staining for FGF23 protein by immunohistochemistry was demonstrated in the giant cell tumor, but not in the angiolipoma. The serum concentration of FGF23 was elevated in preoperative serum, then normalized after removal of the giant cell tumor. Expression of both FGF23 mRNA and protein was demonstrated in the giant cell tumor tissue, and FGF23 mRNA expression and renal phosphate uptake inhibitory activity were also detected in cultured giant cell tumor cells. This case provides further evidence for the involvement of FGF23 in the pathogenesis of oncogenic osteomalacia and for the utility of serum FGF23 measurement and immunohistochemical detection of FGF23 in the diagnosis and clinical management of this condition.

This work was supported by the National Health and Medical Research Council of Australia (to A.E.N., R.S.M., and B.G.R.) and Glaxo SmithKline (to M.M.).

A.E.N. and R.C.B. are joint first authors.

Abbreviations: ADHR, Autosomal dominant hypophosphatemic rickets; FGF, fibroblast growth factor; OOM, oncogenic osteomalacia; RU, reference units.

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