8056 Burosumab Treatment In McCune Albright Syndrome: New Therapeutic Perspectives And Gaps To Be Filled

Abstract Disclosure: A. Barbato: None. R. Vaiasuso: None. G. Del Medico: None. S. Stagi: None. Background: McCune Albright syndrome (MAS) is a sporadic genetic condition associated with bone dysplasia, multiple endocrine over-function, and café au lait skin macules. It is caused by postzygotic mosaic activating mutations of GNAS gene located on chromosome 20q13.3, leading to increased activity of Gs α protein. Fibrous dysplasia (FD) is one of the key features of this syndrome and causes bone deformities with pathologic fractures. In pediatric age, therapies for FD are only able to control pain and reduce burden of disability but not to modify the course of the disease. FGF23 production is increased in MAS and negatively influences bone metabolism. Anti-FGF23 antibody, burosumab, has been recently introduced as a potential new treatment for FD. Case presentation: an 11 years old boy with MAS was referred to our Center for periodic follow-up and treatment of severe FD. He was diagnosed with FD at the age of 1 year and 8 months and since then underwent 4 pathological fractures and 2 surgical interventions for correction of bone deformity. At the age of 6 years old subclinical hyperthyroidism was diagnosed. At the same age he started treatment with endovenous neridronate every three months with partial control of the pain but progression of bone deformity. One year later he developed hypophosphatemia (nadir 3.1 mg/dl) with increased FGF23 levels (144 pg/ml). Because of the clinical worsening of the disease with persistent laboratory alterations (phosphate 3.1 mg/dl, FGF23 251 pg/ml, alkaline phosphatase (ALP) 2188 UI/l, 25-OH vitamin D 58 ng/ml, and PTH 38 pg/ml), at 9 years old he started periodic treatment with burosumab (0.4 mg/kg). The same year the patient developed a central precocious puberty therefore treatment with GnRH was started. After 1 year of treatment with burosumab (0,8 mg/kg) we observed an increase in phosphate levels to 4.2 mg/dl and a reduction of ALP to 1490 UI/L while FGF23 remained stable 243 pg/ml, as did 25 OH vitamin D 31 ng/ml, and PTH 44 pg/ml. At periodic X-rays we documented a slower but still present progression of the FD. Conclusion: burosumab showed beneficial effect on bone tissue metabolism in our patient without significant adverse reactions but did not manage to completely stop FD progression and reduce FGF23 levels. This finding highlights how FGF23 acts as exacerbating factor rather than sole determinat of FD, leading to only a partial clinical response to anti-FGF23 therapy. Furthermore, the presence of FD reduces the efficacy of ALP as a marker of laboratory response, requiring a more disease specific approach to laboratory monitoring of response to burosumab in MAS. New target therapies are needed for Gs α over-function. Presentation: 6/1/2024