Osteoporosis in anorexia nervosa: a brittle future?

Anorexia nervosa commonly occurs during adolescence, a critical period for the acquisition of peak bone mass. Osteopenia is an early and serious complication associated with anorexia nervosa. Whether the osteopenia observed in adolescents with anorexia nervosa is reversible is unknown. The possible mechanisms for the osteopenia observed in adolescents with anorexia nervosa are complex and poorly understood. The purpose of this paper is to review a number of the identified factors that influence the attainment of peak bone mass in anorexia nervosa and to examine the best treatment options for optimizing skeletal mineralization in adolescents with anorexia nervosa.

Starving the brain: structural abnormalities and cognitive impairment in adolescents with anorexia nervosa.

Anorexia nervosa (AN) is one of the most common chronic illnesses afflicting adolescent girls and is associated severe medical complications. The structural abnormalities found in the brain of adolescents with AN are among the earliest and most striking physical consequences. In the past, it had been assumed that the brain abnormalities found in patients with AN reverse with weight-recovery. Recent evidence has shown that not all of these changes are completely reversible with weight recovery. To date, very little is known about the functional significance of these brain abnormalities. Several studies have shown that cognitive dysfunction is also a common feature of AN. Although current evidence suggests that there may be some degree of improvement in cognition with weight-recovery, it is unclear whether cognition recovers fully or equally across all neuropsychological domains. Furthermore, it remains unknown whether the reported functional consequences are associated with these structural brain changes. This article will review the current literature on structural brain abnormalities and cognitive dysfunction in adolescents with AN.

Electrocardiographic findings in adolescents with eating disorders.

OBJECTIVES: We sought to determine the prevalence and clinical correlates of electrocardiographic findings in adolescents with eating disorders. STUDY DESIGN: We undertook matched case-control study of electrocardiographic findings at initial assessment in 62 adolescents with anorexia nervosa, 9 with bulimia nervosa, and 26 with eating disorder not otherwise specified presenting from March 1995 to September 1996. RESULTS: Mean (+/- 1 standard deviation) age was 15.0 +/- 1.4 years (95% were female). Patients with anorexia nervosa had significantly lower heart rates (mean case-control difference: -20 +/- 17 beats per minute), lower R in V(6) (-2.6 +/- 5.5 mm), longer QRS interval (+.004 +/-.010 seconds), shorter mean QTc (-.0136 +/-.033 seconds) and lesser QTc dispersion (-.010 +/-. 031 seconds). The bulimia nervosa group had slightly longer mean QTc (.019 +/-.020 seconds), with no significant case-control differences in the eating disorder not otherwise specified group. CONCLUSION: Electrocardiographic findings are abnormal in adolescents with anorexia nervosa but not in adolescents with bulimia nervosa or eating disorder not otherwise specified.

Use of hormone replacement therapy to reduce the risk of osteopenia in adolescent girls with anorexia nervosa.

PURPOSE: To assess how commonly hormone replacement therapy (HRT) and other measures are prescribed for the treatment of osteopenia in children and adolescents with anorexia nervosa (AN). METHODS: A self-administered questionnaire was distributed and completed by allopathic and osteopathic physician members of the Society for Adolescent Medicine at its 1998 annual meeting. The questionnaire was also mailed and E-mailed between March 1998 and February 1999. Descriptive statistics included percentages and measures of central tendency. RESULTS: The questionnaire was completed by 394 of the 1029 physicians surveyed (38.3%). Of the 268 respondents who treated patients with AN under the age of 18 years, 77.6% prescribed HRT. The decision to prescribe HRT was influenced by patient's age but not by bone mineral status. Among those who prescribed HRT, additional therapies included increased caloric intake (89.4%), weight gain (82.2%), increased calcium intake (84.1%), a change in exercise patterns (59.1%), and vitamin D supplementation (37.0%). Only 59 (22.0%) did not use HRT as a treatment modality. One-third of nonprescribers cited the lack of evidence of efficacy of HRT in preventing osteopenia. More recent medical graduates were less likely to prescribe HRT. CONCLUSIONS: This survey suggests that practitioners caring for adolescent females with AN commonly prescribe HRT for the treatment of osteopenia despite the paucity of evidence demonstrating that it effectively prevents or reverses bone loss associated with this disorder.

Comparison of family therapy and family group psychoeducation in adolescents with anorexia nervosa.

OBJECTIVE: To compare the effects of 4 months of 2 family-oriented treatments, family therapy and family psychoeducation, on female adolescents with newly diagnosed restrictive eating disorders. METHOD: Twenty-five female adolescents requiring hospitalization were randomized into either family therapy or family group psychoeducation. Outcome measures included medical (body weight) and psychosocial (specific and nonspecific eating disorder psychopathology) variables at baseline and after 4 months of treatments every 2 weeks. RESULTS: A significant time effect was found in both treatment groups for the restoration of body weight (percentage of ideal body weight, P < 0.00001). The group averages ranged from 75% to 77% ideal body weight before treatment to 91% to 96% after it. A time effect was also seen on the Family Assessment Measure (P < 0.018), in that the patients of both groups acknowledged more family psychopathology at the end of treatment. No significant group differences were found on any of the self-report measures of specific and nonspecific eating disorder pathology. CONCLUSIONS: Weight restoration was achieved following the 4-month period of treatment in both the family therapy and family psychoeducation groups, but no significant change was reported in psychological functioning by either adolescents or parents. Family group psychoeducation, the less expensive form of treatment, is an equally effective method of providing family-oriented treatment to newly diagnosed, medically compromised anorexia nervosa patients and their families.

Compulsive physical activity in adolescents with anorexia nervosa: a psychobehavioral spiral of pathology.

The excessive exercising that is frequently observed in anorexia nervosa (AN) has been viewed both as an addictive behavior and as a type of obsessive compulsive disorder. The present study tested a nonrecursive structural equation model that specified associations among personality factors, cognitions, and behavior in the development and progression of excessive exercise in adolescent patients with AN. As proposed, findings indicated that both addictive personality and obsessive-compulsive personality contributed to excessive exercising by means of their influence on obligatory/pathological cognitions about exercising. Childhood physical activity also predicted excessive exercising. The implications of these results are discussed from a psychobiological perspective.

Self-assessment of sexual maturation in adolescent females with anorexia nervosa.

PURPOSE: To evaluate the accuracy of self-assessment of pubertal maturation and to determine the desired stage of pubertal maturity in adolescent females with anorexia nervosa. METHODS: Standardized figure drawings depicting Tanner's sexual maturation stages were given to a consecutive sample of 40 adolescent females with anorexia nervosa who were instructed to assess current and desired pubertal development. Pubertal development was assessed independently by two investigators. The percent agreement between physician and subject ratings was determined. RESULTS: Percent agreement between physician and subject ratings was 30% for developmental stage for breasts and 50% for pubic hair. Subjects underestimated breast development 3.4 times as often as they overestimated it and overestimated pubic hair development 1.5 times as often as they underestimated it. Multivariate probit analysis showed that inaccuracy in breast self-assessment was inversely related to a desire for sexual maturity (p < 0.05). Ninety percent of subjects stated that their desired stage of breast development was equal to or more mature than their present stage. Eighty percent stated that their desired stage of pubic hair development was equal to or more mature than their present stage. CONCLUSIONS: Self-assessment of sexual maturity by adolescents with anorexia nervosa using standardized figure drawings depicting Tanner's stages is not accurate. Patients desiring a sexually immature body were most likely to be inaccurate in their self-assessment of their pubertal stage.

The prevalence of high-level exercise in the eating disorders: etiological implications.

There is increasing evidence both from animal experimentation and from clinical field studies that physical activity can play a central role in the pathogenesis of some eating disorders. However, few studies have addressed the issue of prevalence or whether there are different rates of occurrence across diagnostic categories, and the estimates that do exist are not entirely satisfactory. The present study was designed to conduct a detailed examination of the physical activity history in patients with anorexia nervosa (AN) and bulimia nervosa (BN) both during and prior to the onset of their disorder. A sample of adult patients and a second sample of adolescent AN patients took part in the study. A series of chi-square analyses compared diagnostic groups on a number of variables related to sport/exercise behaviors both premorbidly and comorbidly. Data were obtained by means of a detailed structured interview with each patient. We found that a large proportion of eating disorder patients were exercising excessively during an acute phase of the disorder, overexercising is significantly more frequent among those with AN versus BN, and premorbid activity levels significantly predict excessive exercise comorbidity. These findings underscore the centrality of physical activity in the development and maintenance of some eating disorders. They also have important clinical implications in light of the large proportion of individuals who combine dieting and exercise in an attempt to lose weight, and the increasing recognition of the adverse effects of strenuous physical activity in malnourished individuals.

A longitudinal magnetic resonance imaging study of brain changes in adolescents with anorexia nervosa.

OBJECTIVE: To assess whether the cerebral gray and white matter volume deficits described in patients with anorexia nervosa (AN) are fully reversible with weight rehabilitation. DESIGN: A prospective cohort study using magnetic resonance imaging to examine the brains of female adolescents after weight recovery from AN. SETTING: An adolescent eating disorder program located in a tertiary care children's hospital. PARTICIPANTS: Of 13 patients who underwent a previous magnetic resonance imaging study at a low weight, 6 patients were weight recovered and underwent rescanning. All brain measures were corrected for the effects of intracranial volume and age, based on a regression analysis of a group of 34 healthy female control subjects. Scans from the patients with AN were also compared with scans from an age-matched subset of 16 healthy female controls. MAIN OUTCOME MEASURES: White matter volumes, gray matter volumes, and cerebrospinal fluid volumes in the weight-recovered AN group. RESULTS: Quantitative analysis showed that white matter and ventricular cerebrospinal fluid volumes changed significantly (P = .03 for both) on weight recovery from AN. The weight-recovered patients had significant gray matter volume deficits (P = .01) and elevated cerebrospinal fluid volumes (P = .005) compared with those of the age-matched controls. They no longer had significant (P = .30) white matter volume deficits. CONCLUSION: The finding of persistent gray matter volume deficits in patients who have recovered their weight after AN suggests an irreversible component to the structural brain changes associated with AN, in addition to a component that resolves on weight recovery.

Cerebral gray matter volume deficits after weight recovery from anorexia nervosa.

BACKGROUND: Structural changes have been observed in the brains of low-weight patients with anorexia nervosa (AN), including increased cerebrospinal fluid (CSF) volumes and decreased gray matter and white matter volumes. We hypothesized that subjects who are weight-recovered from AN would show elevated CSF volumes and reduced gray matter volumes compared with controls. METHODS: We used magnetic resonance imaging to compare the brains of 12 subjects who are weight-recovered from AN (time since weight recovery, 1-23 years) with those of 18 healthy control subjects and 13 low-weight patients with AN. Axial, dual-echo scans of the whole brain were segmented into gray matter, white matter, and CSF compartments by means of a computerized volumetric approach. Brain measures were corrected for the significant effects of intracranial volume and age, based on regression analysis of a larger group of 30 healthy female controls. RESULTS: Tests showed that the weight-recovered group had significantly greater CSF volumes and smaller gray matter volumes than the control group. By comparison with low-weight patients, the weight-recovered subjects had significantly smaller CSF volumes and significantly larger gray matter and white matter volumes. In the weight-recovered group, neither the CSF elevations nor gray matter deficits were correlated with the length of time since weight recovery. CONCLUSIONS: The persistent gray matter volume deficits in subjects who are weight-recovered from AN suggest that there may be an irreversible component to the brain changes associated with the illness. The neuropathological features of this irreversible component have yet to be characterized.

Cerebral gray matter and white matter volume deficits in adolescent girls with anorexia nervosa.

OBJECTIVES: This study was undertaken to determine whether the increased cerebrospinal fluid (CSF) volumes found in anorexia nervosa (AN) are the result of differences in gray matter or white matter volumes or both. METHODS: Thirteen adolescent girls with AN who were receiving inpatient care at a tertiary-care university children's hospital and eight healthy female control subjects were studied by using magnetic resonance imaging. Images were processed by means of software developed to classify all pixels as either CSF, gray matter, or white matter. Pixels of each class were then summed across all sections. RESULTS: The AN group had larger total CSF volumes in association with deficits in both total gray matter and total white matter volumes. Lowest reported body mass index was inversely correlated with total CSF volume and positively correlated with total gray matter volume. Urinary free cortisol levels were positively correlated with total CSF volume and inversely correlated with central gray matter volume. CONCLUSIONS: These findings add support to the view that the brain abnormalities found in AN are in large part the result of the effects of the illness. The extent to which these differences in gray matter and white matter volumes are reversible with recovery remains to be established.

Clinical and anthropometric correlates of bone mineral acquisition in healthy adolescent girls.

We studied the acquisition of bone mineral in 45 healthy prepubertal and pubertal girls and related changes in bone mass to age, body mass, pubertal status, calcium intake, and exercise. A subgroup of 12 girls was followed longitudinally. Bone mineral content (BMC) of the lumbar spine, whole body, and femoral neck was measured by dual energy x-ray absorptiometry and that at the midradius by single photon absorptiometry. For comparison, spine and whole body mineral contents were also measured by dual photon absorptiometry. Bone mass was expressed in conventional terms of BMC and area density (BMD). However, we show that BMD fails to account for differences in bone thickness. Since bone size increases during adolescence, we present a new expression, bone mineral apparent density (BMAD), which is BMC normalized to a derived bone reference volume. This term minimizes the effect of bone geometry and allows comparisons of mineral status among bones of similar shape but different size. BMC increased with age at all sites. These increases were most rapid in the early teens and plateaued after 16 yr of age. When bone mineral values at all sites were regressed against age, height, weight, or pubertal stage, consistent relationships emerged, in which BMC was most strongly correlated, BMD was correlated to an intermediate degree, and BMAD correlated only modestly or without significance. Dietary calcium and exercise level did not correlate significantly with bone mass. From these relationships, we attribute 50% of the pubertal increase in spine mineral and 99% of the change in whole body mineral to bone expansion rather than to an increase in bone mineral per unit volume. In multiple regressions, pubertal stage most consistently predicted mineral status. This study emphasizes the importance of pubertal development and body size as determinants of bone acquisition in girls. BMAD may prove to be particularly useful in studies of bone acquisition during periods of rapid skeletal growth.

The incidence of Chlamydia pneumoniae lower respiratory tract infections among university students in northern California.

Chlamydia pneumoniae has recently been identified as a cause of lower respiratory tract infections. From March 1987 to March 1988, 259 university students-151 students with lower respiratory tract infections and 108 controls-from the University of California, Berkeley, were studied to determine the incidence and pattern of C pneumoniae lower respiratory tract infections. Serologic evidence of a recent C pneumoniae infection was found in less than 2%, and the organism was not isolated from any of the subjects. Despite the paucity of evidence of a recent infection, 47.5% of this university population showed serologic evidence of a previous C pneumoniae infection. The lower incidence of C pneumoniae infection in our population, when compared with previous reports, suggests that there may be geographic and temporal differences or fluctuations among populations.