Table 6. [Targeted Treatment of Manifestations in Individuals with X-Linked Hypophosphatemia]. - GeneReviews®

Treatment Class	Mechanism of Action	Specific Drugs	Comments
Monoclonal antibody	Target FGF23 to restore renal phosphate reabsorption & ↑ serum concentration of 1,25 dihydroxyvitamin D	Burosumab (Crysvita^®)	In clinical trials, burosumab improved radiographic signs of rickets, lower limb deformity, & height z scores in children compared to phosphate w/active vitamin D supplementation. ¹ At 64 wks (but not at 40 wks), a significant improvement in the 6-min walking test was observed. In adults, burosumab compared to placebo improved joint stiffness & physical function & improved healing of pseudofractures as well as histologic signs of osteomalacia. ²
Oral phosphate w/active vitamin D analogs	Supplementation	Alfacalcidol or calcitriol (vitamin D analogs)	Referred to as conventional therapy (although superiority of burosumab compared to phosphate w/active vitamin D has now been demonstrated in children). ³ Aim of therapy is to improve growth & rickets in children. In adults, this treatment may be considered in case of pseudofractures, bone pain, other symptoms (incl dental abscesses), &/or planned surgery. Biochemically, aim of therapy is to improve circulating phosphate, 1,25-dihydroxyvitamin D levels, & secondary hyperparathyroidism; however, oral phosphate w/active vitamin D analogues aggravates renal phosphate wasting, ↑ urinary calcium excretion w/risk of nephrocalcinosis, & further ↑ FGF23. ⁴

Treatment Class

Mechanism of Action

Specific Drugs

Comments

Monoclonal antibody

Target FGF23 to restore renal phosphate reabsorption & ↑ serum concentration of 1,25 dihydroxyvitamin D

Burosumab (Crysvita^®)

In clinical trials, burosumab improved radiographic signs of rickets, lower limb deformity, & height z scores in children compared to phosphate w/active vitamin D supplementation. ¹ At 64 wks (but not at 40 wks), a significant improvement in the 6-min walking test was observed.
In adults, burosumab compared to placebo improved joint stiffness & physical function & improved healing of pseudofractures as well as histologic signs of osteomalacia. ²

Oral phosphate w/active vitamin D analogs

Supplementation

Alfacalcidol or calcitriol (vitamin D analogs)

Referred to as conventional therapy (although superiority of burosumab compared to phosphate w/active vitamin D has now been demonstrated in children). ³
Aim of therapy is to improve growth & rickets in children. In adults, this treatment may be considered in case of pseudofractures, bone pain, other symptoms (incl dental abscesses), &/or planned surgery.
Biochemically, aim of therapy is to improve circulating phosphate, 1,25-dihydroxyvitamin D levels, & secondary hyperparathyroidism; however, oral phosphate w/active vitamin D analogues aggravates renal phosphate wasting, ↑ urinary calcium excretion w/risk of nephrocalcinosis, & further ↑ FGF23. ⁴

From: X-Linked Hypophosphatemia

GeneReviews^® [Internet].

Adam MP, Feldman J, Mirzaa GM, et al., editors.

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