The effect of anthropometric variables and bone size on bone mineral density (BMD) was examined in 22 children with GH deficiency (GHD) aged 6.1-8.0 yr at diagnosis and in 40 sex- and chronological age-matched controls. In all patients and controls, bone mineral content (BMC), BMDarea and BMD corrected for the apparent bone volume (BMDvolume) were measured by dual-energy x-ray absorptiometry in the lumbar spine at L2-L4 level. In patients, BMDarea was corrected for body height (BMDheight), body mass index (BMDBMI), and bone age (BMDBA). Patients showed significantly reduced (P < 0.0001) BMC (males 11.55 +/- 0.71 g, females 10.13 +/- 1.48 g) and BMDarea (males 0.502 +/- 0.033 g/cm2, females 0.515 +/- 0.034 g/cm2) compared with controls (BMC: males 18.09 +/- 1.23 g, females 15.58 +/- 1.87 g; BMDarea: males 0.689 +/- 0.065 g/cm2, females 0.685 +/- 0.059 g/cm2). In patients, BMDheight (males 0.537 +/- 0.031 g/cm2, females 0.548 +/- 0.032 g/cm2) and BMDBMI (males 0.641 +/- 0.028 g/cm2, females 0.624 +/- 0.035 g/cm2) remained significantly lower (P < 0.02 to P < 0.0001) than BMDarea of controls. BMDBA of patients was significantly reduced (-1.49 +/- 0.51 Z score, P < 0.0001) in comparison with bone age-matched controls (n = 35). BMDvolume was significantly lower (P < 0.01 to P < 0.0005) in patients (males 0.268 +/- 0.006 g/cm3, females 0.276 +/- 0.010 g/cm3) compared with chronological age-matched controls (males 0.283 +/- 0.013 g/cm3, females 0.293 +/- 0.017 g/cm3). Mean bone volume of patients was affected to a greater extent than bone area (-2.36 +/- 0.49 Z score and -1.56 +/- 0.70 Z score, respectively). Bone area/bone volume ratio was significantly higher in patients than in chronological age-matched controls (0.53 +/- 0.02 and 0.42 +/- 0.08, P < 0.0001, respectively). Chronological age, body height, BMI, and bone age correlated significantly with BMDarea (r2 = 0.389-0.450, P < 0.002 to P < 0.001) but not with BMDvolume (P = not significant). The results show that anthropometric variables and bone size affect lumbar BMC and BMDarea in children with GHD. Reduced lumbar BMDvolume indicates that apparent true bone density is decreased in children with GHD, suggesting a role of GH in bone mineralization.