Calcimimetics as adjunct therapy in XLH: 18 months experience

Uri Alon; Connie Haney

doi:10.1530/boneabs.2.OP3

Objective: Based on our preliminary findings, indicating a potential for Cinacalcet (due to its suppression of PTH (CJASN 2008 3 658)), to allow the use of lower doses of oral phosphate (OP) and calcitriol in treating XLH, the objective of this study was to examine its long-term effect as adjunct treatment in children with XLH.

Methods: Eight children (F5), ages 7.8–20.9 years (median 13.9), who were already treated by OP and calcitriol were enrolled in the study. Cinacalcet was added at 30 mg once daily to those weighing ≤30 kg and 60 mg to those >30 kg. Clinic visits were done every 3 m; dose of medications adjusted to maintain serum P similar to baseline, PTH within its normal range and Ca⁺⁺>1.00 mmol/l. In case of hypercalciuria (>4 mg/kg per 24 h) a thiazide/amiloride preparation was added. Blood was checked for creatinine, Ca⁺⁺, P, Alk. Phosph., PTH and FGF23; and urine for TP/GFR and Ca excretion. Radiographs of lower joints were done every 6 months and renal ultrasound annually.

Results: Follow-up lasted 21.2±5.3 m (median 18).

Table 1
	Start	End	P
Calcitriol dose (ng/kg per 24 h)	22.0±12.0	12.5±8.9	<0.001
K-Phos dose (mg/kg per 24 h)	40.4±24.4	23.3±20.7	<0.01
PTH (pg/ml)	45.0±38.8	21.9±16.3	<0.05
Ca⁺⁺(mmol/l)	1.20±0.06	1.06±0.07	<0.005
P (mg/dl)	3.01±0.31	3.10±0.41	NS
AlK. Phos. (μ/l)	242±160	196±120	0.06
FGF23 (RU/ml)	272±71	197±82	<0.005
TP/GFR (mg/dl)	2.24±0.33	2.49±0.41	<0.005
Urine Ca (mg/kg per 24 h)	1.9±1.4	1.1±0.7	NS

Conclusions: The addition of the calcimimetic: i) resulted in significant decreases in PTH and FGF23 and increase in TP/GFR enabling significant decreases in calcitriol and OP doses and ii) requires careful attention to serum and urine calcium. Further studies are warranted exploring the beneficial effects of calcimimetics in the treatment of children with XLH.

Rickets stayed healed in all. Nephrocalcinosis grade one was present at baseline and did not change in one child, and in another developed after 2 years into the study. Serum creatinine was normal in all. At the end of the study, seven children were receiving Cinacalcet 30 mg, and the oldest 60 mg. Three children had their growth plates closed at start. Height SDS improved in two patients, were unchanged in two and decreased in one. One child was on thiazide/amiloride at baseline and in three it was added during the study. No side effects were observed and none of the patients discontinued the study.

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