Growth Hormone Therapy: a Panacea for Hypophosphatemic Rickets?† 406

Abstract

Conventional therapy of hypophosphatemic rickets (HR) with oral phosphate and calcitriol does not always result in normal linear growth and may cause nephrocalcinosis. Adjunctive therapy with recombinant human growth hormone(rhGH) offers theoretical advantages with respect to both of these limitations of conventional therapy. In this report 5 prepubertal children (aged 3.5-10.9 yrs) with well-controlled HR on conventional therapy were given adjunctive rhGH therapy (0.03 mg/kg/day, 6 days a week) for one year. All patients had been receiving conventional therapy (oral phosphate supplements [mean dose± SD: 74.5 ± 14.0 mg/kg/day] in 5 divided doses and 1,25(OH)2D(calcitriol, [mean dose ± SD: 66.6 ± 15.3 mgm/kg/day] as a single night time dose) for at least 1 year with a mean duration of 5.2 years. Prior to enrolment in the study all patients had adequate improvement of metabolic bone disease as defined by normocalcemia, PTH levels 10-65 ng/l and normal alkaline phosphatase (ALP) and creatinine levels. Radiologically their growth plates at the wrist and knee were characterised by only minimal rachitic changes.Biochemical GH deficiency was not detected in any patient after L-dopa/propanolol stimulation testing.The pre-rhGH treatment height SD(HtSD) scores were negative in all patients (mean HtSD score = -2.2). Pre-rhGH treatment growth velocity SD (GVSD) scores were positive in 4/5 patients (mean GVSD score = +0.6). Height, growth velocity, serum phosphate, ionized calcium, ALP and PTH levels, urinary calcium/creatinine excretion ratios, tubular reabsorption of phosphate body composition, bone mineral density, radiologic changes of the growth plates and renal sonographic appearances were assessed at regular intervals. Height and growth velocities were also calculated 12 months after ceasing rhGH therapy. After 12 months adjunctive therapy with rhGH no significant biochemical or radiologic benefits were observed. There was a significant increase in the mean height SD score (mean HtSD score =-1.9, p=0.023). There was no change in the mean GVSD score after 1 year of rhGH treatment (mean GVSD score=+0.6). Thus, rhGH therapy did not appear to increase the rate of catch-up growth caused by conventional therapy alone. When rhGH therapy was ceased no significant decreases in mean height SD or growth velocity SD scores were observed (mean HtSD score= -1.8, mean GVSD score=+0.3). We conclude that in well controlled HR patients receiving conventional therapy, adjunctive therapy with standard dose rhGH appears to offer no benefits with respect to either linear growth or rachitic disease markers.