Alendronate for the treatment of osteopenia in anorexia nervosa: a randomized, double-blind, placebo-controlled trial.

Osteopenia is a serious medical complication of anorexia nervosa, with no known effective treatment. We conducted a double-blinded, randomized trial comparing alendronate (10 mg daily) with placebo in 32 adolescents with anorexia nervosa (mean age, 16.9 +/- 1.9 yr). All subjects received 1200 mg elemental calcium and 400 IU vitamin D daily and received the same multidisciplinary treatment for their eating disorder. Bone mineral densities (BMDs) of the lumbar spine and femoral neck were measured by dual energy x-ray absorptiometry at baseline and after 1 yr of treatment. Twenty-nine subjects completed the study. Femoral neck and lumbar spine BMDs increased 4.4 +/- 6.4% and 3.5 +/- 4.6% in the alendronate group compared with increases of 2.3 +/- 6.9% and 2.2 + 6.1% in the control group (P = 0.41, femoral neck; P = 0.53, lumbar spine). From baseline to follow-up, BMD increased significantly at the femoral neck (P = 0.02) and lumbar spine (P = 0.02) in those receiving alendronate, but did not increase in those assigned placebo (P = 0.22, femoral neck; P = 0.18, lumbar spine). At follow-up, body weight was the most important determinant of BMD. BMD was significantly higher in subjects who were weight-restored compared with those who remained at low weight (P = 0.002, femoral neck; P = 0.04, lumbar spine). After controlling for body weight, treatment group assignment still had an independent effect at the femoral neck. We conclude that in adolescents with anorexia nervosa, weight restoration is the most important determinant of BMD, but treatment with alendronate did increase the BMD of the lumbar spine and femoral neck within the group receiving alendronate, but not compared with placebo in the primary analysis. Until additional studies have demonstrated efficacy and long-term safety, the use of alendronate in this population should be confined to controlled clinical trials.

Resolution of vital sign instability: an objective measure of medical stability in anorexia nervosa.

PURPOSE: To determine the amount of time necessary for stabilization of blood pressure and heart rate in patients with anorexia nervosa (AN) and the percentage of ideal body weight (IBW) at which this occurs. METHODS: A retrospective study was conducted on 36 adolescent patients (33 F, 3 M) with AN, restricting type (Diagnostic and Statistical Manual of Mental Disorders, Fourth edition [DSM-IV] criteria), admitted to a specialized eating disorders unit for nutritional rehabilitation between October 1996 and August 1998. Mean age was 16.5 +/- 2.5 years, range 12-23 years. Each morning, pulse and blood pressure were measured supine and after standing for 2 minutes using an automated blood pressure/pulse measuring device (Dynamap). Orthostasis was defined as a drop in systolic blood pressure > 20 mm Hg with or without a drop in diastolic blood pressure > 10 mm Hg or an increase in heart rate >20 bpm on standing. Time of resolution of orthostasis was defined as the day after which the patient was no longer orthostatic for 48 hours. RESULTS: On admission mean pulse rate was 54.4 +/- 14.8 bpm (range 38-78) and mean pulse rate slowly increased to 70 bpm by Day 12 of hospitalization. On admission, 60% of patients had orthostatic pulse changes and with refeeding, this number increased to 85% by Day 4 of admission. The mean number of days until patients were no longer orthostatic was 21.6 +/- 11.1 days and resolution of orthostasis occurred when subjects reached 80.1 +/- 5.7% of IBW. Orthostatic pulse changes were more sensitive indicators of hemodynamic instability than orthostatic blood pressure changes and took longer to resolve. CONCLUSION: This study demonstrates that of patients with AN, the majority have orthostatic pulse changes on admission. Normalization of orthostatic pulse changes was achieved after approximately 3 weeks of nutritional rehabilitation when subjects reached 80% of their IBW. Resolution of orthostasis can be used as one of the objective measures to determine medical stability and readiness for discharge to an alternate level of care.

Hypophosphatemia during nutritional rehabilitation in anorexia nervosa: implications for refeeding and monitoring.

PURPOSE: To determine the incidence of hypophosphatemia in adolescents with anorexia nervosa (AN) hospitalized for nutritional rehabilitation and to examine factors predisposing to its development. METHODS: A retrospective chart review of 69 patients (66 female, 3 male) with AN consecutively admitted to an inpatient adolescent medical unit between July 1, 1998 and June 30, 2000. Mean age was 15.5 +/- 2.4 (range 8 to 22) years and mean % ideal body weight (IBW) was 72.7 +/- 7%. Serum phosphorus was measured daily for 1 week and then biweekly to weekly. Patients were started on 1200-1400 kcal/day and calories were increased by 200 kcal every 24-48 hours. RESULTS: Four (5.8%) patients developed moderate hypophosphatemia (<2.5 and > or = 1.0 mg/dl) and 15 (21.7%) had mild hypophosphatemia (<3.0 and > or = 2.5 mg/dl). Patients who developed moderate hypophosphatemia were significantly more malnourished than those who did not (p = 0.02). Phosphorus nadirs were directly proportional to % IBW (r = 0.3, p = 0.01). Over three-quarters of the patients (81%) reached their phosphorus nadir within the first week of hospitalization. The patient with the lowest phosphorus level experienced short runs of ventricular tachycardia. No other severe complications were seen. Overall, 19 (27.5%) patients required phosphorus supplementation. CONCLUSIONS: Phosphorus drops to its nadir during the first week of refeeding. We recommend daily monitoring of serum phosphorus with supplementation as needed during the first week of hospitalization, especially in those who are severely malnourished.

The effect of estrogen-progestin treatment on bone mineral density in anorexia nervosa.

INTRODUCTION: Osteopenia is a serious complication of anorexia nervosa (AN). Although in other states of estrogen deficiency, estrogen replacement therapy increases bone mass, its role in AN remains unresolved. STUDY OBJECTIVE: To study the effect of estrogen-progestin administration on bone mass in AN. DESIGN, SETTING, AND PARTICIPANTS: A prospective observational study of 50 adolescents with AN (mean age 16.8 +/- 2.3 yrs) was conducted in a tertiary referral center. MAIN OUTCOME MEASURES: Bone mineral density (BMD) of the lumbar spine and left hip were prospectively measured using dual-energy x-ray absorptiometry at baseline and annually. INTERVENTIONS: Twenty-two subjects received estrogen-progestin and 28 standard treatment (Rx) alone. Estrogen-progestin was administered daily as an oral contraceptive containing 20-35 mcg ethinyl estradiol. All subjects received calcium supplementation and the same medical, psychological, and nutritional intervention (standard Rx). Mean length of follow-up was 23.1 +/- 11.4 months. RESULTS: At presentation, patients were malnourished (79.5% +/- 7.6% IBW), hypoestrogenemic (estradiol 24.7 +/- 10.7 pg/mL), and had reduced bone mass (lumbar spine BMD -2.01 +/- 0.69 SD below the young adult reference mean). Ninety-two percent of subjects were osteopenic and 26% met WHO criteria for osteoporosis. Body weight, and no treatment group, was the major determinant of BMD. At one-year follow-up, there were no significant differences in absolute values or in net change of lumbar spine or femoral neck BMD between those who received estrogen-progestin and those who received standard Rx (80% power of finding a 3% difference in BMD at 1 yr). In those followed for 2-3 yrs, osteopenia was persistent and in some cases progressive. CONCLUSION: In our study population, estrogen-progestin did not significantly increase BMD compared with standard Rx. These results question the common practice of prescribing hormone replacement therapy to increase bone mass in AN.