Efficacy of growth hormone therapy for patients with skeletal dysplasia

Most patients with skeletal dysplasia show severe short stature. Surgical therapy has been attempted to correct bone deformities, but therapy for improving their severe short stature has been rarely attempted. We undertook a clinical trial of growth hormone (GH) therapy for patients with skeletal dysplasia accompanying severe short stature caused by achondroplasia (ACH), hypochondroplasia (HCH), pseudoachondroplasia (PSACH), spondyloepiphyseal dysplasia congenita (SED), or Schmid type metaphyseal dysplasia (MD). This study examined the efficacy of GH therapy on height increase and change of height SD score over a 1-year period in patients with skeletal dysplasia and showed a short-term efficacy for skeletal dysplasia. In ACH, HCH, and MD, GH had a significant effect on height gain. However, PSACH and SED showed no height gain efficacy; in cases of PSACH, height SD score was worse after therapy. Severe adverse events were not observed except in one SED case, in which scoliosis worsened and height did not increase. For patients with skeletal dysplasia, GH therapy is moderately effective for height gain. It is ineffective in cases with severe spinal deformities, however; although bone growth was promoted, the ligaments and matrix were too weak to support muscle tonus and the effects of gravity, resulting in worsened kyphosis and lordosis. These results clarify why GH therapy is ineffective for height gain. The pathogenic genes of skeletal dysplasia have recently been detected and consequently changes in bone formation have been investigated in detail. Careful consideration of indications for therapy and cautious observation during therapy are crucial when attempting to treat advanced bone deformities.