Childhood growth hormone deficiency, bone density, structures and fractures: scrutinizing the evidence

Abstract

Childhood-onset growth hormone deficiency (GHD) is frequently perceived to cause low bone density, fractures and osteoporosis. This article critically reviews the evidence behind these perceptions. Inherent limitations of current bone imaging techniques have caused many artefacts and misconceptions about bone density and structure. Using appropriate size-corrections, bone density is normal in children and adults with isolated GHD. Cortical density, trabecular density and trabecular volume are normal when measured by peripheral quantitative computerized tomography and histomorphometry. The only verifiable deficit affects cortical thickness (periosteal expansion), both in human and animal studies. However, short limb bones cannot be expected to have an average-sized shaft, as bone elongation and widening could be proportionally impaired in GHD. In addition, GH and IGF-1 have indisputable anabolic actions not only on bone, but also on muscle tissue. In fact, compared with all other bone-related variables, muscle size is the lowest at diagnosis of GHD. During GH therapy, muscle enlargement precedes and exceeds any gain in bone mass. The mechanostat theory suggests that the GHD-induced deficit in muscle force secondarily causes low cortical thickness. There is no evidence that isolated childhood-onset GHD, or severe GH resistance, causes an increased fracture risk in children or adults. Only adults with organic hypopituitarism appear to have a slightly greater risk of fractures. Using current transition guidelines, short children and adults with GHD are at risk of being misdiagnosed with low bone mass and may consequently receive inappropriate treatment. As neither reports of increased fracture risk nor low bone density can stand up against scrutiny, these misconceptions should no longer influence clinical practice. In this respect, GHD should not be listed as a cause of osteoporosis in children and there is a need to review current transition guidelines.