Burosumab treatment for fibroblast growth factor-23-associated hypophosphatemia in an adult patient with severe fibrous dysplasia in McCune-Albright syndrome: case report and review of the literature.

Abstract

McCune-Albright syndrome (MAS) is a rare mosaic genetic disorder caused by a mutation in the GNAS gene and typically presents with a triad of symptoms: fibrous dysplasia of bones, café-au-lait macules, and precocious puberty. The GNAS mutation leads to overproduction of fibroblast growth factor-23 (FGF23), which may result in hypophosphatemia. Burosumab, a monoclonal antibody against FGF23, is approved for the treatment X-linked hypophosphatemia and tumor-induced osteomalacia. There are currently no data on its efficacy and safety in fibrous dysplasia/MAS patients. A 27-yr-old male with MAS was under the care of the Endocrinology Department for persistent hypophosphatemia and skeletal complications despite treatment with oral phosphate supplements and calcitriol. He started treatment with burosumab (1 mg/kg s.c. every 4 wk) and achieved normalization of calcium-phosphate metabolism (phosphate 0.83 mmol/L vs 0.38 mmol/L; PTH 70.4 pg/mL vs 177 pg/mL) and significant reduction in alkaline phosphatase activity (ALP 620 IU/L vs 1182 IU/L) and bone fraction of alkaline phosphatase activity (BALP 327 IU/L vs 603 IU/L). No further fractures were observed during 24 mo of treatment. The patient reported a reduction in bone pain and improved well-being. No adverse effects were reported during treatment. This is the first reported case of burosumab treatment in an adult patient with fibrous dysplasia/MAS. The therapy had positive effects on the patient's well-being, calcium-phosphate balance, and bone markers. However, longer follow-up and further safety studies are needed before routine use in adult fibrous dysplasia/MAS patients.