Treatment of achondroplasia with growth hormone: Six years of experience

Abstract

We describe the effects of recombinant hGH (r-hGH) therapy for up to 6 y on stature and body proportions of 35 children with achondroplasia (Ach). Consecutive height (Ht) measurements were plotted on disease-specific Ach growth curves, but age and sex SD scores (SDS) of Ht, sitting Ht, subischial leg length, and Ht velocity were made with respect to Tanner normal standards. r-hGH was administered by daily subcutaneous injections at a median (range) dose of 30 (15.8-40) U/m2 per week [0.06 (0.04-0.08) mg·kg-1~.24 h-1]. Patients were treated for 3 (1-6) y from age 2.25 (1.2-9.3) y. Before treatment, Ht SDS was -4.6 (-6.5 to -3.24). Treatment caused a significant increase in Ht SDS year to year until y 4 (ANOVA F = 46.94; p < 0.01) that was subsequently sustained with no significant further change (y 5 and 6 versus y 4, p > 0.05). When the response to r-hGH was also expressed as a change in Ht velocity, there was a significant increase in the first year of therapy that was maintained over subsequent treatment years (ANOVA = 4.28, p = 0.001). Age was the most important variable accounting for the first-year response in Ht SDS (r2 = 0.41, p < 0.001), and dose of r-hGH did not influence this. Increments in sitting Ht SDS were greater than subischial leg length SDS (F = 26.25, p < 0.001; F = 9.04, p < 0.001, respectively), r-hGH treatment improved the Ht position of Ach children relative to their normal and Ach peers without obvious side effects. A young age at initiation of therapy prevented the characteristic Ht deficit from accumulating. The greater increase in spinal Ht accentuated the existing disproportion. The addition of later surgical leg lengthening could offer the possibility of proportionate adult stature just within the normal range.