RESUMEN
Young women with anorexia nervosa (AN) have subnormal levels of dehydroepiandrosterone (DHEA) and estrogen that may be mechanistically linked to the bone loss seen in this disease. The purpose of this study was to compare the effects of a 1-yr course of oral DHEA treatment vs. conventional hormonal replacement therapy (HRT) in young women with AN. Sixty-one young women were randomly assigned to receive oral DHEA (50 mg/d) or HRT (20 micro g ethinyl estradiol/0.1 mg levonorgestrel). Anthropometric, nutrition, and exercise data were acquired every 3 months, and bone mineral density (BMD) and body composition were measured by dual energy x-ray absorptiometry (DXA) every 6 months over 1 yr. Serum samples were obtained for measurements of hormones, proresorptive cytokines, and bone formation markers, and urine was collected for determinations of bone resorption markers at each visit. In initial analyses, total hip BMD increased significantly and similarly (+1.7%) in both groups. Hip BMD increases were positively correlated with increases in IGF-I (r = 0.44; P = 0.030) and the bone formation marker, bone-specific alkaline phosphatase increased significantly only in the DHEA treatment group (P = 0.003). However, both groups gained significant amounts of weight over the year of therapy, and after controlling for weight gain, no treatment effect was detectable. There was no significant change in lumbar BMD in either group. Both bone formation markers, bone-specific alkaline phosphatase and osteocalcin, increased transiently at 6-9 months in those subjects receiving DHEA compared with the estrogen-treated group (P < 0.05). Both DHEA and HRT significantly reduced levels of the bone resorption markers, urinary N-telopeptides (P < 0.05). There was a positive correlation between changes in IGF-I and changes in weight, body fat determined by DXA, and estradiol for both groups. In addition, patients receiving DHEA exhibited improvement on three validated psychological instruments (Eating Attitudes Test, Anorexia Nervosa Subtest, and Spielberger Anxiety Inventory). Both DHEA and HRT had similar effects on hip and spinal BMD. Over the year of treatment, maintenance of both hip and spinal BMD was seen, but there was no significant increase after accounting for weight gain. Compared with HRT, DHEA appeared to have anabolic effects, evidenced by the positive correlation between increases in hip DXA measurements and IGF-I and significant increases in bone formation markers. Both therapies significantly decreased bone resorption. Replicating results from studies of the elderly, DHEA resulted in improvements in specific psychological parameters in these young women.
Asunto(s)
Anorexia Nerviosa/tratamiento farmacológico , Densidad Ósea/efectos de los fármacos , Deshidroepiandrosterona/uso terapéutico , Tejido Adiposo , Adolescente , Adulto , Fosfatasa Alcalina/sangre , Anorexia Nerviosa/complicaciones , Anorexia Nerviosa/psicología , Composición Corporal , Imagen Corporal , Peso Corporal , Colágeno/orina , Colágeno Tipo I , Ingestión de Energía , Estradiol/sangre , Terapia de Reemplazo de Estrógeno , Etinilestradiol/administración & dosificación , Femenino , Humanos , Levonorgestrel/administración & dosificación , Ciclo Menstrual , Fenómenos Fisiológicos de la Nutrición , Osteocalcina/sangre , Osteoporosis/etiología , Osteoporosis/prevención & control , Péptidos/orinaRESUMEN
OBJECTIVE: To clarify the role of physiologic regulators of bone turnover in patients with anorexia nervosa (AN). STUDY DESIGN: Adolescent girls with AN (n = 61) had anthropometric, nutrition, and exercise data acquired, and bone mineral density (BMD) and body composition measured by dual energy x-ray absorptiometry. Serum samples were obtained for hormones, proresorptive cytokines, and bone formation markers, and urine for bone resorption markers. RESULTS: In bivariate correlation analyses, significant (P <.05) predictors of lumbar BMD included height, weight, and exercise. In multiple regression models, these significant relationships held, even after controlling for the duration of amenorrhea and AN. For total body BMD, the same positive predictors were found and percentage of body fat was a negative correlate. For hip BMD, exercise and weight were found to be positive predictors. Dehydroepiandrosterone sulfate (DHEAS) was inversely correlated with N-telopeptides (NTx), and insulin-like growth factor I (IGF-I) was directly correlated with osteocalcin. Proresorptive cytokine levels were low or undetectable. CONCLUSIONS: Exercise and weight were positive predictors of BMD. These data are the first to suggest a relationship between DHEAS and increased bone resorption in AN. IGF-I was correlated with bone formation indices. Low cytokine levels suggest that these factors do not mediate the increased bone resorption of AN.
Asunto(s)
Anorexia Nerviosa/complicaciones , Densidad Ósea/fisiología , Resorción Ósea/etiología , Resorción Ósea/fisiopatología , Osteogénesis/fisiología , Adolescente , Biomarcadores , Citocinas/sangre , Sulfato de Deshidroepiandrosterona/sangre , Ejercicio Físico , Femenino , Humanos , Factor I del Crecimiento Similar a la Insulina/metabolismo , Análisis Multivariante , Análisis de RegresiónRESUMEN
OBJECTIVE: Clinical depression is associated with multiple abnormalities of immune function, including reduced virus-specific responses. This study tested the hypothesis that the Flinders Sensitive Line (FSL) rat, a promising genetic animal model of depression, would exhibit reductions in antigen-specific primary antibody responses to immunization. METHODS: FSL (N = 13) and control Flinders Resistant Line (FRL; N = 14) rats were immunized with the protein antigen keyhole limpet hemocyanin (KLH; 300 microg/kg), and KLH-specific immunoglobulin (Ig)M, IgG, IgG1, and IgG2a responses were measured before and 3, 5, 7, 11, and 14 days after immunization. In separate experiments, production of interferon-gamma (IFN-gamma) by cells from naive and KLH-immunized animals was measured in vitro to determine whether strain differences in antibody production might be associated with differential production of this regulatory cytokine. RESULTS: KLH-specific production of IgM (p <.01) and IgG2a (p <.05) was significantly reduced in the FSL rats compared with the FRL controls. There were no strain differences in IgG or IgG1 production. Although IFN-gamma production between the two strains was similar in naive animals, cells from KLH-immunized FSL rats produced significantly less IFN-gamma when stimulated with KLH in vitro than cells from KLH-immunized FRL controls (p =.01). CONCLUSIONS: This study extends previous reports of altered immune function in the FSL rats to include reduced in vivo antigen-specific antibody responses. Moreover, diminished production of IFN-gamma by KLH-primed lymphocytes may contribute to lower antibody production in these animals. Collectively, these data suggest deficiencies in type 1 T-helper cell-mediated immunity in the FSL rats.