Effective treatment of hyperphosphatemia with denosumab in patients with loss of function of FGF23 and high bone density: case series

Objectives This study evaluated denosumab for treating hyperphosphatemia in patients with loss-of-function FGF23 mutations and high bone density. Methods Three patients with hyperphosphatemia due to mutations in the FGF23 pathway (two FGF23 , one GALNT3 ) were treated. Conventional therapies, including phosphate binders, dietary restriction, and teriparatide, failed to reduce phosphate in the two symptomatic FGF23 patients. Denosumab, a RANKL inhibitor that decreases bone resorption, was administered for more than two years. Results Denosumab result in a marked and sustained reduction in serum phosphate in all three patients. The two symptomatic patients experienced significant relief from bone pain and improved appetite and well-being. Serum calcium decreased in all patients, with asymptomatic hypocalcemia seen in two cases. Bone density decreased in one patient and was unchanged in another. No significant side effects were observed, except for hypocalcemia. Conclusions Denosumab effectively reduced serum phosphate and improved symptoms in patients with FGF23 -related hyperphosphatemia that was resistant to standard treatments. Denosumab may represent a promising new therapy for treatment-resistant hyperphosphatemia in FGF23 pathway disorders, though further studies are needed to confirm these findings and determine optimal management strategies.