Body Composition and Bone Mineral Density in Adolescents with Partial Growth Hormone Deficiency

The major role of GH during childhood is to promote longitudinal bone growth. Besides growth, GH affects body composition, bone mineralization, and lipid metabolism. GH deficiency (GHD) in children, as well as in adults, is associated with increased fat mass and decreased lean body mass (mainly muscles) and bone mass (1, 2). It has been reported that during GH therapy of children with GHD fat mass normalized within 6 months (1). Height, lean tissue mass, and bone mass increased during GH treatment but were still significantly lower than normal after 6 yr of treatment (3). The tallest reported mean final height of GH-deficient children treated with recombinant human GH was −0.7 sd below mean height (4). Early diagnosis and sufficient treatment improve final height and may also improve normalization of lean body mass and bone mass, by permitting catch-up growth. At final height, patients are retested for GHD using the diagnostic criteria for GHD in adults, because a substantial proportion of patients, especially those with idiopathic isolated GHD, treated with GH during childhood show a normal GH status at final height (5). The criteria for GHD in adults differ specifically from children with respect to the cut-off peak GH level during the GH stimulation test. Rates of GH secretion reach maximum levels by mid-puberty; thereafter, GH secretion declines rapidly with age (5). Therefore, the peak GH levels in the stimulation test are lower in adults than in children. Most agree that a GH peak response <3 μg/liter in the insulin tolerance test (ITT) is diagnostic for GHD in adults vs. 5–10 μg/liter in children (5). A consensus is reached to treat GH-deficient adults with GH to prevent long-term consequences, such as increased central adiposity, decreased lean body mass, osteoporosis, enhanced cardiovascular risk, and reduced quality of life. Indeed, recent studies have shown that adolescents with childhood onset GHD who continued to be severely GH deficient lost lean body mass when GH was discontinued, whereas healthy adolescents of similar ages demonstrated increased lean body mass and muscle strength (6). Another study reported a significant decrease in muscle strength and an increase in fat mass in adolescent patients after cessation of GH (7). It is noteworthy that lumbar spine bone mineral density (BMD), corrected for bone area, was significantly reduced at final height in treated patients with childhood onset GHD, but lumbar spine BMD corrected for bone volume did not differ from normal (8). This may be explained by the fact that areal BMD is dependent on bone size and, therefore, related to height, whereas volumetric BMD is not. In most studies, final height of the treated GH-deficient patients is less than that of the control population. The prevalence of fractures did not differ between patients and controls (8). Lumbar spine BMD and total body bone mineral content continued to build up in patients with childhood onset GHD who proceeded with GH treatment at completion of linear growth but remained stable in patients who discontinued GH (9). These studies show that complete muscle and bone maturation is reached at a later stage than final height. Lean body mass and bone mass continue to increase for about 2–3 yr after epiphyseal fusion (3, 5). Bone mass is associated with muscle mass, and, therefore, increase of muscle mass is of importance in the attainment of peak bone mass. Bone mass later in life is determined by peak bone mass acquired during adolescence and the subsequent rate of bone loss. Osteoporosis is a major public health problem involving postmenopausal women and aging individuals, and low peak bone mass results in a higher risk of osteoporosis. Therefore, the acquisition of adequate bone mass during childhood is essential to prevent osteoporosis later in life.