Shelly Levi ^1* Daniel Landau ^1,2 Miriam Davidovits ^1,2 Mika Shapira Rootman ³ Avivit Brener ^2,4 Shoshana Gal ^5,6 Yael Borovitz ¹ Ori Goldberg ^2,7 Rachel Bello ⁸ Roxana Cleper ^2,9 Yael Lebenthal ^2,4 Yael Levy-Shraga ^10,2 Dov Tiosano ^5,6 Ravit Regev ^2,4 Adi Chezana ¹¹ Leonid Zeitlin ¹²

• ¹ Pediatric Nephrology Institute, Schneider Children's Medical Center, Petach Tikva, Israel
• ² School of Medicine, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
• ³ Department of Medical Imaging, Rambam Health Care Campus, Haifa, Haifa, Israel
• ⁴ Institute of Endocrinology and Metabolism, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel
• ⁵ Division of Pediatric Endocrinology, Ruth Rappaport Children's Hospital, Rambam Medical Health Care Campus, Haifa, Israel
• ⁶ The Ruth and Bruce Rappaport Faculty of Medicine, Technion Israel Institute of Technology, Haifa, Haifa, Israel
• ⁷ Institute of Pulmonology, Schneider Children’s Medical Center, Petach Tikva, Israel
• ⁸ The Jesse Z and Sara Lea Shafer Institute for Endocrinology and Diabetes, National Center for Childhood Diabetes, Schneider Children’s Medical Center, Petach Tikva, Israel
• ⁹ Pediatric Nephrology Unit, Dana-Dwek Children's Hospital, Tel Aviv Sourasky Medical Center, Tel- Aviv, Israel
• ¹⁰ Pediatric Endocrinology Unit, The Edmond and Lily Safra Children's Hospital, Chaim Sheba Medical Center, Tel-Hashomer, Israel
• ¹¹ Goldman School of Medicine, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel
• ¹² Pediatric Orthopedic Department, Dana-Dwek Children's Hospital, Tel Aviv Sourasky Medical Center, Tel-Aviv, Israel

Background: X-linked hypophosphatemic rickets (XLH) is associated with uninhibited FGF23 activity, which leads to phosphaturia, hypophosphatemia and depressed active vitamin D (1,25OH2D) levels. Conventional treatment with phosphate supplements and vitamin D analogs may lead to hypercalciuria (HC), nephrocalcinosis (NC) and hyperparathyroidism. We investigated the effects of burosumab treatment, an anti-FGF23 monoclonal antibody recently approved for XLH, on these complications.Methods: This retrospective study included children with XLH who were treated with burosumab for at least one year at one of three referral centers. Clinical and biochemical potential treatment outcomes were regularly followed, including multiple urine calcium measurements and NC severity score (0= no NC, 3= worse NC).Results: Twenty-six (13 male) children aged 7.6±3.9 years were followed for 27.5±9.6 months. Mean serum phosphate levels rapidly increased from 2.67±0.61 at baseline to 3.57±0.53 mg/dL after 3 months (p< 0.001) and remained stable thereafter. Concomitant decreases were observed in phosphaturia, serum alkaline phosphatase and parathyroid hormone. HC (U-Ca/Cr > 0.2 mg/mg) was detected in 2/26 (7.7%) patients before burosumab initiation, resolved in one and persisted, albeit improved, in the second. Two patients were newly diagnosed with HC, 15 and 3 months after therapy, which persisted in one of them despite dose reduction attempts. Seven patients had NC at baseline (mean score: 1.8±0.34), but none showed deterioration or developed new NC.In children with XLH treated with burosumab, HC was a rare side effect and preexisting NC did not worsen.