165- How to treat a child with X-linked hypophosphatemic rickets–osteomalacia?
The cornerstone in the management of XLH is phosphate supplementation. The
recommended dose of oral phosphate is 15–60 mg/Kg/day in three to five divided
doses. In addition, calcitriol should also be given at doses of 15–60 ng/Kg/day in
three to four divided doses and adequate calcium intake should be ensured. The
goal of therapy is to maintain serum phosphate in low normal range (to avoid
metastatic calcification), normalization of alkaline phosphatase, restoration of
growth velocity, and healing of rickets. In addition, serum iPTH should be main-
tained in normal range. The management of autosomal dominant and recessive
forms of hypophosphatemic rickets–osteomalacia is similar to XLH.- What is the rationale of calcitriol supplementation in addition to phosphate
therapy in patients with XLH?
Patients with XLH have decreased 1α-hydroxylase activity due to elevated
FGF-23. Further, therapy with phosphate may result in hypocalcemia and sec-
ondary hyperparathyroidism. The concurrent administration of calcitriol not
only increases intestinal calcium and phosphate absorption but also prevents
development of secondary/tertiary hyperparathyroidism. - How to monitor a child with XLH on therapy?
A child with X-linked hypophosphatemic rickets–osteomalacia should be clini-
cally monitored by improvement in bone pain, growth velocity, and deformi-
ties. Biochemical monitoring includes serum phosphate, serum ALP, iPTH, and
urinary phosphate. Serum phosphate should be maintained in the low normal
range, as attempts to normalize serum phosphate are associated with gastroin-
testinal adverse events and development of secondary/tertiary hyperparathy-
roidism. Estimation of urinary phosphate helps in the assessment of compliance
to therapy. Monitoring of FGF-23 is not useful as phosphate and calcitriol ther-
apy may result in further elevation of serum FGF-23. With successful therapy,
decrease in bone pain occurs within few weeks and normalization of ALP
within 6–12 months. There is also increase in growth velocity by 1 year and
improvement of deformities by 3–4 years of age.- What are the alterations in serum iPTH in patients with XLH?
Serum iPTH levels are usually normal/mildly elevated in patients with X-linked
hypophosphatemic rickets–osteomalacia. Rise in iPTH is possibly due to FGF-
23-mediated inhibition of 1,25(OH) 2 D. After initiation of phosphate therapy,
secondary/tertiary hyperparathyroidism may ensue as a result of phosphate-
mediated hypocalcemia and direct stimulatory effect of phosphate on parathy-
roid cell. This is deleterious as it will result in worsening of phosphaturia and
consequently, hypophosphatemia. Overzealous treatment with calcitriol results
in suppression of PTH and consequently hypercalciuria and nephrocalcinosis.5 Rickets–Osteomalacia