Hypophosphatemic Rickets in Fibrous Dysplasia / McCune-Albright Syndrome After Phosphate Salts and Active Vitamin D Have Not Achieved Treatment Goals
Clinical Scenario
This protocol addresses patients with fibrous dysplasia caused by an activating GNAS gene mutation (McCune-Albright syndrome) who develop hypophosphatemic rickets as a result of renal phosphate wasting, and who continue to have persistent skeletal complications despite conventional first-line therapy.
Key Comorbidities
Fibrous Dysplasia
Activating GNAS Gene Mutation
McCune-Albright Syndrome
Renal Phosphate Wasting
Previous Line — Goals Not Reached
First-line management with phosphate salts and active vitamin D (calcitriol or alphacalcidiol) was attempted. Despite this conventional supplementation, the following targets were not achieved: normalization of serum phosphate, normalization of serum alkaline phosphatase, and clinically meaningful improvement in bone pain, muscle weakness, and walking ability. Persistence of hypophosphatemia and skeletal complications defines the escalation threshold for this next-line protocol.
Next-Line Approach — Partial Overview
The next-line protocol involves a targeted biological therapy. Clinical goals include:
- Normalization of serum phosphate
- Normalization of serum alkaline phosphatase
- Improvement of bone pain, muscle weakness, and walking ability
The complete regimen, eligibility criteria, and full clinical algorithm are available in the structured protocol below.
References
DOI: 10.1007/s00467-022-05505-5
Treatment of patients with fibrous dysplasia (FD), which is due to activating mutations in the GNAS gene causing McCune-Albright syndrome primarily focuses on non-rickets complications.
Treatment with phosphate salts and active vitamin D may be considered in patients presenting with hypophosphatemic rickets due to renal phosphate wasting.
Burosumab treatment resulted in normalization of serum phosphate and ALP levels and improvement of clinical symptoms (bone pain, muscle weakness, walking ability) in a patient with FD showing persistent hypophosphatemia and skeletal complications despite oral supplementation with phosphate and treatment with active vitamin D.