To assess the implications of prolonged growth hormone deficiency (GHD) for the acquisition and maintenance of bone mass, bone mineral density (BMD) was measured in 70 adult males (mean age 26.7 +/- 4.5 years) with childhood-onset GHD, 7.4 +/- 4.2 years after discontinuation of previous GH therapy. Because most of these patients were short (mean height 165.8 +/- 6.6 cm), the influence of body height on standard BMD measurements, conventionally reported as the areal density (BMDarea, expressed in g/cm2), was analyzed in a group of age-matched healthy males. In GHD patients, BMDarea was significantly reduced at the lumbar spine (Z score -1.59 +/- 1.08, p < 0.001) as well as at the nondominant hip (Z score -1.18 +/- 0.95, p < 0.001). The reduction in BMDarea was similar for patients with isolated GHD (N = 25) and those with combined deficiencies of GH and luteinizing hormone (N = 40). In patients and controls, BMDarea was positively correlated with body height, a relation that was attributed to skeletal size. Bone dimensions were significantly smaller in patients than in controls, and therefore it was hypothesized that the difference in areal density between patients and controls might be confounded by differences in bone size. Measured bone mineral content corrected for the estimated bone volume (BMDvolume, expressed in g/cm3) remained significantly reduced (Z score: lumbar spine, -0.90 +/- 1.08, p < 0.001; femoral neck, -0.74 +/- 1.00, p < 0.001), but the differences between GHD patients and controls were less than indicated by BMDarea (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)