Elevated serum FGF23 concentrations in plasma cell dyscrasias

Abstract

Fibroblast growth factor 23 (FGF23) is now recognized as a key regulator of phosphate metabolism. Numerous reports have found elevated serum FGF23 concentrations in oncogenic osteomalacia associated with mesenchymal tumors. Hypophosphatemic osteomalacia more rarely occurs in non-mesenchymal tumors. We identified elevated serum FGF23 levels in one patient with chronic lymphatic leukemia (CLL) and hypophosphatemia, prompting us to examine FGF23 concentrations in other patients with B-cell neoplasms. FGF23 levels were elevated in several patients with myeloma and monoclonal gammopathy of undetermined significance (MGUS), and were significantly associated with serum paraprotein and beta-2 microglobulin concentrations in these patients. Hypophosphatemia was not observed even in those patients with elevated FGF23, and a weak positive correlation was noted between serum FGF23 and phosphate concentrations. Malignant plasma cells in bone marrow trephines from patients with myeloma showed cytoplasmic expression of FGF23, similar to the cytoplasmic localization of FGF23 already described in mesenchymal tumors associated with oncogenic osteomalacia. Our findings contribute to an expanding literature regarding abnormal FGF/FGF receptor-signaling in myeloma. The absence of hypophosphatemia in these cases suggests either that FGF23 produced by clonal B-cells lacks systemic bioactivity or that other factors contribute to maintain serum phosphate. We suggest that the relationship between FGF23 and skeletal disease associated with plasma cell dyscrasias deserves further study.