Growth and growth hormone therapy in children with achondroplasia: A two-year experience

Abstract

The efficacy and safety of recombinant human growth hormone (hGH) administration was studied in children with achondroplasia. Fifteen children with achondroplasia, seven boys (4.8-12.2 years of age) and 12 girls (5.7-2.2 years of age), were treated daily with hGH at a dosage of 1 IU/kg/week. Auxological assessments were performed 6 months before, at initiation of, and at 6, 12, and 24 months following initiation of growth hormone (GH) therapy. Before initiating GH therapy, hypothalamic-pituitary and thyroid functions were evaluated. Levels of serum insulin-like growth factor (IGF)-I and IGF binding protein (BP)-3 (IGFBP-3) were assessed, as was GH response to provocative stimuli. GH responses in two stimulation tests were normal for all but three children. During the first semester of GH treatment, a significant increase in height velocity (HV), from 3.2 to 8.3 cm/year, was observed in all children. However, during the second semester, a relative decrease in growth rate was observed. By the end of the first year, HV had increased from 3.2 to 6.9 cm/year (mean, 3.7 cm/year; range, 1.1-8 cm/year) in 13 children and remained unchanged in two children. HV declined progressively during the next 12 months and, by the end of the second year of treatment, had increased in seven of the nine children who had completed 2 years of therapy (mean increase, 3.1 cm/year); two children did not respond to GH therapy, as shown by the lack of increase in HV. Sitting-height (SH) to standing-height ratio % (SH%) remained unchanged throughout GH therapy, and no significant change in skeletal maturation was observed. In conclusion, hGH treatment resulted in an increased growth rate in some children with achondroplasia; however, this increase waned during the second year of treatment. Children with the lowest pretreatment HVs seemed to benefit most from GH therapy. Nonetheless, the usefulness of GH treatment in achondroplasia will be known only when a study of final height is completed.

Growth hormone treatment in 35 prepubertal children with achondroplasia: A five-year dose-response trial

“…Likewise, in the study of Tanaka et al and Stamoyannou et al, relative sitting height was not significantly changed during the study period, but the ratio of lower limb length to height was significantly increased, i.e. improved [8,9]. In the evaluation of 145 treated individuals by Seino et al, an improvement of leg-to-height ratio, from 37.6% to 39.1% following the first year of treatment, was found [10].…”

“…Already in 1933, in Denmark, a treatment experiment was done using pituitary extracts in a patient with chondrodystrophy (presumably achondroplasia) [5]. Several studies since the introduction of recombinant growth hormone have reported short-term (up to 2 y) treatment data on smaller groups of children with achondroplasia [6][7][8][9][10]. Only one study has reported on long-term treatment of these children [11].…”

Interventions for improving clinical outcomes and health-related quality-of-life for people living with skeletal dysplasias: an evidence gap map

“…Out of the 58 included studies, four were randomised control trials [ 22 , 32 , 53 , 54 ], 25 were retrospective case studies [ 5 , 23 – 25 , 27 , 28 , 30 , 34 , 35 , 39 , 41 , 42 , 45 , 46 , 48 , 49 , 57 , 59 , 65 – 69 , 71 , 73 ], 15 were retrospective cohort studies [ 20 , 21 , 26 , 29 , 31 , 36 , 38 , 40 , 47 , 55 , 58 , 60 , 61 , 70 , 74 ], eight were controlled before and after studies [ 15 , 51 , 52 , 56 , 62 – 64 , 72 ], two were prognostic studies [ 19 , 37 ], and one study was a non-randomised control trial [ 50 ]. There were three cross-sectional studies that used patient focused surveys [ 33 , 43 , 44 ].…”

Advances in understanding etiology of achondroplasia and review of management

“…Growth hormone plays an important role in regulating linear skeletal growth by promoting chondrocyte proliferation directly or indirectly through insulin-like growth factor-1. The majority of growth hormone trials in children with achondroplasia have been short-term [46][47][48][49][50][51][52]. These studies report an increase in growth velocity (65-75%) during the first year or a gain of 0.2-0.5 SD of height during the first year of treatment.…”