Introduction 1 Gastrointestinal disorders Gastrointestinal diseases may impact bone health in several ways. Poor calcium intake, as in patients with a milk allergy, and reduced calcium absorption, as in patients with untreated celiac disease, result in low BMD. Early correction of the underlying deficiency allows normal bone mineralization to occur. In addition to poor calcium absorption, inflammatory bowel disease likely impacts bone health through other factors including chronic diarrhea, decreased lean tissue mass, reduced physical activity, increased inflammatory cytokines, and CS therapy. As in all chronic conditions, correction of short stature and delayed maturation will allow better identification of those patients with abnormal DXA findings who will have significant bone mineral deficits. Milk allergy 2 3 4 Inflammatory bowel disease 5 6 7 8 Celiac disease 9 10 11 12 Liver disease 13 14 15 Renal diseases Chronic kidney disease results in abnormal bone metabolism via disturbances in calcium and phosphate handling, altered vitamin D and parathyroid hormone levels and function, and altered renal clearance of other metabolites. Additional factors that affect the BMD in these patients include malnutrition, metabolic acidosis, anemia and growth hormone abnormalities resulting in growth retardation. As with many chronic medical conditions, short stature will greatly affect BMD and needs to be accounted for in DXA interpretation. 16 17 18 19 20 21 18 22 24 25 28 25 26 In summary, the various metabolic disturbances resulting from altered renal physiology may compromise normal bone mineralization and remodeling, but children with chronic kidney disease often maintain normal BMD if calcium and vitamin D metabolism are normal. CS treatment, either before transplantation or when used to suppress transplant rejection, appears to contribute to low BMD but short-term follow-up indicates eventual normalization of LS BMD. Regardless of the nature of renal disease, correcting for height is essential for accurate interpretation of DXA results in these patients. Endocrinological diseases 29 30 31 Disorders of growth hormone, insulin and glucocorticoids 1 32 33 34 33 34 33 35 36 37 38 39 40 41 42 43 44 45 46 Disorders of reproductive hormones 47 48 49 51 51 52 54 53 55 56 57 58 59 60 61 62 In summary, hormonal imbalances from any of a large number of endocrine disorders are associated with abnormal DXA findings and reduced BMD. With hormone replacement therapy, improved bone mineral accrual is to be expected in most of the endocrine deficiencies. However, with anorexia nervosa, especially with onset in adolescence, there appears to be a sustained reduction in BMD even after resumption of normal caloric intake and menses. Respiratory diseases Cystic fibrosis 63 65 66 67 68 66 69 70 71 72 73 Asthma 74 77 78 79 Hematological diseases Anemia and hemophilia 80 81 82 83 84 85 86 87 88 Oncological diseases Acute lymphocytic leukemia 89 90 91 92 93 94 In summary, children with ALL will have reduced BMD during treatment and shortly thereafter. The recuperative capacity in young children is high and normal BMD should be expected even after high-dose methotrexate and CS therapy. The role of adequate physical activity is being increasingly stressed as an important factor in normal BMD recovery. Children who have survived ALL may be at risk of persistently low BMD in adulthood if they have confounding factors such as gonadal dysfunction or if the course of their disease coincided with the period of expected rapid accrual of bone mineral that normally occurs during puberty. Other malignancies 95 96 97 98 99 100 In summary, there are multiple factors that affect short- and long-term BMD in these patients/survivors. These include pubertal status at diagnosis, type of malignancy, local (sarcomas, central nervous system tumors) versus systemic (leukemia) disease, initial (malnutrition, immobilization) versus prolonged (amputation) disease-related disability, types of chemotherapy, and radiation ports and dosages that may cause gonadal or growth hormonal dysfunction. Neurological diseases Cerebral palsy 101 102 103 104 105 106 107 In summary, children with CP show decreased bone mineral status that reflects the duration and severity of their disease. Distal femoral measurements better reflect the bone status at the sites more at risk of fracture. Bisphosphonate therapy increases BMD during treatment and it appears to have sustained benefits with reduced fracture rates even after treatment is terminated. Meningomyelocele 108 109 110 Connective tissue diseases Juvenile rheumatoid arthritis and systemic lupus erythematosus 111 112 113 114 115 116 117 In summary, prepubertal children with JRA of mild or moderate severity without a history of CS treatment will have TBBMD similar to healthy children. With increasing disease severity and duration, especially through puberty, TBBMC will decrease when compared to normal children. 118 119 Musculoskeletal diseases For normal mineralization to occur, adequate muscle-induced mechanical stresses are required to induce bony remodeling. Insufficient muscle mass and activity result in poor bone accrual and low BMD. Additionally, therapy of primary muscle disorders with CS also inhibits normal bone mineralization. Duchenne muscular dystrophy and dermatomyositis 120 121 122 In summary, patients with Duchenne muscular dystrophy have reduced LS BMD, especially in the setting of CS treatment. The low LS and hip BMD worsen with loss of ambulatory status and are frequently associated with fractures of the lower extremities. 123 124 123 Osteogenesis imperfecta 125 126 125 127 130 129 131