XLH is characterized by phosphate wasting due to increased activity of which mediator?

• A. Elevated PTH
• B. Elevated fibroblast growth factor 23 (FGF23)
• C. Increased calcitriol production
• D. Decreased alkaline phosphatase activity

Answer: (B)

In XLH, phosphate wasting is driven by increased activity of FGF23, a phosphaturic hormone. FGF23 acts on the kidney to reduce phosphate reabsorption in the proximal tubule by downregulating the sodium-phosphate co-transporters NaPi-IIa and NaPi-IIc, leading to phosphaturia. It also suppresses 1-alpha-hydroxylase (CYP27B1), lowering calcitriol production, which decreases intestinal phosphate (and calcium) absorption and worsens bone mineralization. This combination explains the hypophosphatemia and defective bone mineralization seen in XLH. Elevated PTH can cause phosphate loss too, but XLH specifically features excess FGF23 activity; increased calcitriol would not fit since calcitriol is reduced in XLH; and decreased alkaline phosphatase activity is not characteristic of the bone turnover seen in this condition.