Differential skeletal outcome of gene therapy and HCT. (A-B) Pictures (A) and 3-dimensional reconstructions of CT scans (B) from MPS I, WT, HCT, and GT mice 6 months after treatment, showing the different gross appearance of the treated and control mice (the GT mouse shown in panels A and B had a VCN of 5.4 on bone marrow; the HCT mouse had a donor-cell engraftment of 74% on PBMCs). (C-F) Measurements of skull width (C), zygomus volume (D), femur length (E), and humerus width (F) were performed on CT scan images, as shown on the right side of each chart (see “CT” for details) from MPS I (n = 19), HCT (n = 14), GT (n = 15), and WT (n = 14). For avoiding sex biases, the femur length of only the male mice was reported (MPS I n = 10, HCT n = 10, GT n = 8, and WT n = 8); similar results were obtained in females. (G) Gene therapy–treated mice were divided into 2 groups according to the IDUA activity measured on their PBMCs. The femur length is shown for animals (males and females) having PBMC IDUA activity lower (<) or higher (>) than 1500 nmol/mg/h (1500 nmol/mg/h is the average activity value measured in the entire population of gene therapy–treated mice). (H) SSI (calculated as described in the “Peripheral quantitative CT”) was evaluated by pQCT on the diaphysis of the femur (left chart) and tibia (right chart) from MPS I (n = 19), HCT (n = 14), GT (n = 15), and WT (n = 14). Mean and min/max values are shown: *P < .05; **P < .01; ***P < .001 with 1-way ANOVA (C-F,H); *P < .05 with Student t test (G).