Objective: We wished to clarify whether the osteopenia reported in adult men with a history of constitutional delay of growth and puberty (CDGP) could be due to the delayed puberty or an independent predisposition to osteoporosis in this condition. Design: Short prepubertal children with CDGP and children with familial short stature (FSS) were matched for height and other auxological variables. The FSS children served as a control group. Methods: We measured spinal (L1-L4) bone mineral content (BMC) and bone mineral density (BMD) by dual energy X-ray absorptiometry (Hologic QDR 1000/w) in 56 children aged 5-11 years. All children had height below the 10th percentile for chronological age (CA), and bone age (BA) less than 10 years, 29 of them with clinical diagnosis of possible CDGP and 27 of them with FSS. The BMD standard deviation scores (SDS) relative to the values for normal height children were obtained. Results: The mean (Ϯ S.D.) spinal BMD was significantly lower in the children with CDGP than in the FSS group (0.534 Ϯ 0.059 vs 0.623 Ϯ 0.060 g/cm 2 , P < 0.001). Both groups had negative mean lumbar BMD SDS, but in the CDGP group it was significantly lower than in the FSS group as well when the SDS was based on the CA (¹1.41 Ϯ 0.61 vs ¹0.38 Ϯ 0.51, P < 0.001) and when it was related to BA (¹0.78 Ϯ 0.64 vs ¹0.17 Ϯ 0.52, P < 0.01). BMC was significantly lower in the CDGP than in the FSS group, when multiple regression analysis was performed by using scanned bone area, body weight and height, sex and BA as independent variables (P ¼ 0.0005). Conclusion:The finding of decreased mineralization in prepubertal children with CDGP before the age of puberty suggests that they may have an inherent predisposition to osteopenia.