RESUMO
BACKGROUND: Bone mass is under strong genetic control, and recent studies in adults have suggested that allelic differences in the gene for the vitamin D receptor may account for inherited variability in bone mass. We studied the relations of the vitamin D-receptor genotype to skeletal development and variation in the size, volume, and density of bone in children. METHODS: We identified three allelic variants of the vitamin D-receptor gene using the polymerase chain reaction and three restriction enzymes (ApaI, BsmI, and TaqI) in 100 normal prepubertal American girls of Mexican descent. We then determined the relations of the different vitamin D-receptor genotypes (AA, Aa, aa, BB, Bb, bb, TT, Tt, and tt) to the cross-sectional area, cortical area, and cortical bone density of the femoral shaft and the cross-sectional area and density of the lumbar vertebrae. RESULTS: The vitamin D-receptor genotype was associated with femoral and vertebral bone density. Girls with aa and bb genotypes had 2 to 3 percent higher femoral bone density (P=0.008 and P=0.04, respectively) and 8 to 10 percent higher vertebral bone density (P=0.01 and P=0.03, respectively) than girls with AA and BB genotypes. There was no association between the cross-sectional area of the vertebrae or the cross-sectional or cortical area of the femur and the vitamin D-receptor genotype. The chronologic age, bone age, height, weight, body-surface area, and body-mass index did not differ significantly among girls with different vitamin D-receptor genotypes. CONCLUSIONS: Vitamin D-receptor gene alleles predict the density of femoral and vertebral bone in prepubertal American girls of Mexican descent.
Assuntos
Densidade Óssea/genética , Americanos Mexicanos/genética , Receptores de Calcitriol/genética , Alelos , Criança , Feminino , Fêmur/fisiologia , Genótipo , Humanos , Polimorfismo Genético , Coluna Vertebral/fisiologia , Tomografia Computadorizada por Raios XRESUMO
Forty children and adults with classic galactosemia had vertebral bone density determined by standard quantitative computed tomography at 3.4 to 44.2 years of age. Compared with age- and sex-matched control subjects, patients with galactosemia had diminished bone density (p = < 0.001). Prepubertal patients of both sexes had bone density determinations below those of the control group (p = 0.008); similar findings were seen in postpubertal patients as well (women, p = 0.001; men, p = 0.008). Women receiving replacement estrogen-progestin therapy for premature ovarian failure had abnormal bone density (136.3 +/- 17.3 mg/cm3 vs 166.0 +/- 17.5 mg/cm3 for control subjects; p = 0.002); patients with evidence of ovarian insufficiency not receiving replacement sex steroids had even lower bone density (92.4 +/- 14.3 mg/cm3 vs 160.2 +/- 20.2 mg/cm3 for control subjects; p < 0.001). Calcium intake for the entire galactosemia group was 540 +/- 344 mg/day. Calcium intake correlated positively with bone density in women given exogenous estrogen (r = 0.87; p = 0.002) and in men (r = 0.74; p = 0.009). Thus the diminished mineralization of bones appears to be another abnormality associated with galactosemia. The results of our study suggest that this is likely secondary to abnormal levels of sex steroids in female patients, low calcium intake, and perhaps an intrinsic defect in the normal galactosylation of the collagen matrix of bone caused by the enzyme defect. Strategies to improve bone formation should be considered to diminish morbidity in patients with this inborn error of metabolism.
Assuntos
Densidade Óssea/fisiologia , Cálcio/deficiência , Galactosemias/metabolismo , Hipogonadismo/metabolismo , Adolescente , Adulto , Cálcio/metabolismo , Criança , Pré-Escolar , Dieta , Feminino , Galactosemias/diagnóstico por imagem , Galactosemias/fisiopatologia , Humanos , Masculino , Tomografia Computadorizada por Raios XRESUMO
A prospective study was conducted to investigate the possibility of osteoporosis after treatment for childhood acute lymphoblastic leukemia (ALL). Forty-two survivors of ALL had the trabecular bone density of the spine evaluated by quantitative computed tomography, 6 to 98 months (mean 42 months) after completion of chemotherapy. The ALL survivors had significantly lower bone density than age-, gender-, and race-matched nonleukemic control subjects had (10% less, p less than 0.001); this decrease was accounted for solely by the subset of patients who had received cranial irradiation (n = 30; p less than 0.001). The relative reduction in bone density in ALL survivors was unrelated to age at the time of diagnosis or time without therapy. The effects on bone density of 18 Gy and of 22.5 to 25.2 Gy were indistinguishable. We conclude that survivors of ALL commonly have reduced bone density in the lumbar spine and suggest that the diminution is related to nervous system irradiation, not to the disease or to chemotherapy.
Assuntos
Neoplasias Meníngeas/prevenção & controle , Osteoporose/etiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/radioterapia , Radioterapia de Alta Energia/efeitos adversos , Densidade Óssea , Criança , Feminino , Humanos , Vértebras Lombares/diagnóstico por imagem , Masculino , Estudos Prospectivos , RadiografiaRESUMO
To determine if osteoporosis is prevalent among patients with cystic fibrosis, we compared the vertebral bone density measured by quantitative computed tomography in 57 such patients (29 male, 28 female, aged 3 to 21 years) with those of an age-, race-, and sex-matched control group of 57 healthy subjects. Patients with cystic fibrosis had significantly lower bone density (10% lower, p less than 0.001) than in controls. The decrease in bone density in patients with cystic fibrosis was unrelated to age. Shwachman clinical evaluation scores (based on case history, pulmonary physical findings, growth, and x-ray findings) correlated positively with age-standardized bone density values (p less than 0.01). Male patients had substantially lower bone density than did female patients (p less than 0.02), but bone density differences related to gender were not significant when effects of disease severity were controlled for. Decreased bone density was more common in patients with poor nutritional status as determined by anthropometric measurements (p less than 0.05). We conclude that osteoporosis is a frequent complication in children with cystic fibrosis regardless of their age and is more prevalent in patients with greater disease severity.
Assuntos
Fibrose Cística/complicações , Osteoporose/etiologia , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Vértebras Lombares/diagnóstico por imagem , Masculino , Minerais , Osteoporose/diagnóstico por imagem , Fatores Sexuais , Tomografia Computadorizada por Raios XRESUMO
We have observed the development of chronic inflammatory bowel disease, indistinguishable from Crohn disease, in two boys with glycogen storage disease type Ib (GSD-Ib). A chance association of these diseases in two patients is unlikely. Studies of their neutrophils showed severe chronic neutropenia (mean absolute granulocyte counts of less than 500 cells/microliter) and markedly deficient chemotactic response (less than 5% of reference values) in the patients with GSD-Ib and normal neutrophil values in four patients with glycogen storage disease type Ia (GSD-Ia). Monocyte counts and responses to chemotactic stimulation were normal in both GSD-Ia and GSD-Ib. Chronic inflammatory bowel disease appears to be associated with GSD-Ib, and neutrophil abnormalities may be involved in the pathogenesis of the bowel inflammation.