Osteopenia is common in children, adolescents, and young adults with severe cerebral palsy (CP; spastic quadriplegia) living in residential care, and frequently results in atraumatic fractures. On clinical grounds 67 patients (34 males, 33 females) with severe CP (gross motor function classification system [GMFCS] levels IV or V) aged 5 to 25 years (median 20 y) were divided into three groups with increasing likelihood of severe impairment of bone quality: (1) patients without fractures and without anticonvulsant medication (n=13); (2) patients without fractures and with anticonvulsant medication (n=45); (3) patients with fractures and with anticonvulsant medication (n=9). Evaluation included measurements of quantitative ultrasound (QUS) of the calcaneus, multiple serum analyses, and determination of urinary bone-resorption markers. Values of the quantitative ultrasound index (QUI) were significantly different (p=0.001): group 1 (median 56.9; interquartile range 43.8-75.3); group 2 (49.9; 40.0-60.0); group 3 (35.6; 30.5-38.5). when comparing values of laboratory serum and urine in the three groups, we found significant differences in values of serum bone alkaline phosphatase (p=0.001), serum parathyroid hormone (PTH; p=0.002), serum albumin (p=0.020), and urinary deoxypyridinoline/creatinine ratio (p=0.004). In multiple regression analysis, no laboratory variable was found to be an independent predictor of QUI. QUS of the calcaneus may be a useful method to assess bone quality and fracture risk in children and young adults with severe cp living in residential care, independent of information from laboratory data.