What is the treatment and management approach for a male patient with X-linked hypophosphatemia, characterized by low phosphate levels, softening of the bones, and a family history of similar bone health issues?

Treatment and Management of X-Linked Hypophosphatemia

First-Line Treatment Recommendation

Burosumab is the preferred first-line treatment for X-linked hypophosphatemia in both children and adults, offering superior efficacy and improved quality of life compared to conventional phosphate and vitamin D supplementation. 1

Pre-Treatment Requirements

Before initiating burosumab therapy, you must:

• Discontinue oral phosphate and active vitamin D analogs (calcitriol, paricalcitol, doxercalciferol, calcifediol) 1 week prior to starting treatment 2
• Confirm fasting serum phosphorus is below the reference range for age 2
• Obtain genetic testing of the PHEX gene for diagnosis confirmation, or measure intact FGF23 levels if genetic testing is unavailable 1
• Calculate TmP/GFR to document renal phosphate wasting, with fractional phosphate excretion >15% confirming the diagnosis 1
• Exclude Fanconi syndrome by testing for glucosuria, aminoaciduria, and low molecular weight proteinuria 1

Burosumab Dosing Protocol

For Pediatric Patients (6 months to <18 years):

• Patients <10 kg: Start with 1 mg/kg subcutaneously every 2 weeks, rounded to nearest 1 mg 2
• Patients ≥10 kg: Start with 0.8 mg/kg subcutaneously every 2 weeks, rounded to nearest 10 mg (minimum 10 mg, maximum 90 mg) 2
• Maximum injection volume is 1.5 mL per site; use multiple sites if needed 2

Dose Adjustments:

• Monitor fasting serum phosphorus every 4 weeks for the first 3 months, then as appropriate 2
• For patients <10 kg: Increase to 1.5 mg/kg if phosphorus remains below reference range, with maximum dose of 2 mg/kg 2
• For patients ≥10 kg: Increase stepwise up to approximately 2 mg/kg (maximum 90 mg) if phosphorus remains below reference range 2
• Do not adjust dose more frequently than every 4 weeks 2

For Adult Patients:

Burosumab is FDA-approved for adults with XLH, administered subcutaneously by a healthcare provider 2

Comprehensive Monitoring Protocol

Initial Phase (First 3 Months):

Monitor every 4 weeks: 1

• Fasting serum phosphorus
• Serum calcium
• Creatinine
• Alkaline phosphatase
• Parathyroid hormone (PTH)

Ongoing Monitoring:

• Regular radiological assessment for rickets severity, osteomalacia, and pseudofractures 1
• Growth parameters (height, weight, BMI) in children 1
• Regular dental surveillance for abscesses and periodontitis 1

Multidisciplinary Care Coordination

All patients require care organized by a metabolic bone disease expert with a multidisciplinary team including: 1

• Metabolic bone disease specialist
• Nephrologist
• Orthopedic surgeon
• Dentist

This team approach is essential for monitoring renal complications, skeletal deformities, and dental problems 1

Management of Specific Complications

Prevention of Secondary Hyperparathyroidism:

Burosumab eliminates the need for phosphate and vitamin D supplementation, thereby preventing secondary hyperparathyroidism 1. This is a major advantage over conventional therapy, which often causes this complication.

Musculoskeletal Symptoms:

Physical therapy focused on pain relief, improving function, and reducing disability is essential 1. Patients with XLH commonly experience fatigue, decreased motion, muscle weakness, and pain that significantly impact quality of life 3

Growth Considerations:

For children with compromised height prognosis despite burosumab therapy, continuing recombinant human growth hormone (rhGH) after switching to burosumab may be beneficial for final height 4. The combination appears safe, with one study showing continued height gain (mean 0.2 ± 0.1 SDS) during combined therapy 4. However, burosumab alone shows minimal height improvement (mean 0.0-0.1 SDS change after 1 year) 4

Special Populations

Pregnant and Lactating Women:

Specialized management protocols are recommended for pregnant and lactating women with XLH 1

Transition to Adult Care:

Genetic counseling should be offered to patients, especially during transition to adult care 1

Critical Pitfalls to Avoid

• Never continue phosphate supplements or active vitamin D analogs concurrently with burosumab 2 - this is a contraindication
• Do not initiate burosumab if serum phosphorus is not below the reference range for age 2
• Avoid measuring FGF23 after starting phosphate or vitamin D therapy, as these treatments influence levels 5
• Remember that age-related reference ranges for serum phosphorus must be used, as infant levels may appear normal in the first 3-4 months despite underlying disease 5