Although children with MPS I, II, and VI who are treated with hematopoietic cell transplantation (HCT) and/or enzyme replacement therapy (ERT) are now living into adulthood with good cognitive development, their quality of life is significantly impacted by their skeletal abnormalities (i.e., kyphosis, scoliosis, genu valgum), joint contractures, pain, and severe short stature. Additional therapies (e.g., post-HCT supplemental ERT, anti-TNFα drugs, stop codon suppression drugs, gene therapy) to decrease the burden of skeletal disease and improve growth are needed. However, prior to these therapeutic studies, control data quantifying the progression of skeletal disease in individuals with MPS I, II and VI treated with ERT and/or HCT are needed, along with biomarkers to be used as early predictors of response to treatment.