Which agent is used to treat X-linked hypophosphatemia (XLH) by targeting FGF23?

Which agent is used to treat X-linked hypophosphatemia (XLH) by targeting FGF23?

• A. Calcitriol
• B. Burosumab
• C. Alendronate
• D. Teriparatide

Answer: (B)

X-linked hypophosphatemia is driven by excess FGF23, which causes the kidneys to waste phosphate and lowers the production of active vitamin D, leading to low serum phosphate and poor bone mineralization. The treatment that directly counters this mechanism is burosumab, a human monoclonal antibody that binds FGF23 and blocks its activity. By neutralizing FGF23, burosumab reduces renal phosphate wasting, increases phosphate reabsorption in the proximal tubule, and allows 1,25-dihydroxyvitamin D levels to rise, which further improves intestinal phosphate absorption. The net effect is higher serum phosphate and better bone mineralization in XLH. Other options don’t target FGF23. Calciferol (calcitriol) provides active vitamin D to help with mineral balance but does not inhibit FGF23 itself. Alendronate is a bisphosphonate that reduces bone resorption rather than addressing the phosphate-wasting signal. Teriparatide stimulates bone formation through PTH pathways but does not correct the underlying FGF23-driven phosphate wasting.

X-linked hypophosphatemia is driven by excess FGF23, which causes the kidneys to waste phosphate and lowers the production of active vitamin D, leading to low serum phosphate and poor bone mineralization. The treatment that directly counters this mechanism is burosumab, a human monoclonal antibody that binds FGF23 and blocks its activity. By neutralizing FGF23, burosumab reduces renal phosphate wasting, increases phosphate reabsorption in the proximal tubule, and allows 1,25-dihydroxyvitamin D levels to rise, which further improves intestinal phosphate absorption. The net effect is higher serum phosphate and better bone mineralization in XLH.

Other options don’t target FGF23. Calciferol (calcitriol) provides active vitamin D to help with mineral balance but does not inhibit FGF23 itself. Alendronate is a bisphosphonate that reduces bone resorption rather than addressing the phosphate-wasting signal. Teriparatide stimulates bone formation through PTH pathways but does not correct the underlying FGF23-driven phosphate wasting.