Tbe effects of anorexia nervosa on bone metabolism in female adolescents

Osteopenia is a frequent, often persistent, complication of anorexia nervos a (AN) in adolescent girls and occurs during a critical time in bone develo pment. Little is known about bone metabolism in this patient population. Th erefore, we measured bone density (BMD) and body composition by dual energy x-ray absorptiometry, nutritional status, bane turnover, calcium; and horm onal status in 19 adolescent girls with AN (mean +/- SEM, 16.0 +/- 0.4 yr) and 19 bone age-matched controls. The mean duration of AN was 19 +/- 5 mont hs. Spinal (L1-L4) osteopenia was common in AN. Lumbar anterioposterior BMD was more than 1 sn below the mean in 42% of patients, and lateral spine BM D was more than 1 SD below in 63% of patients compared with controls. Lean body mass significantly predicted lumbar bone mineral content (r = 0.75; P < 0.0001) in controls only. In AN, duration of illness was the most signifi cant predictor of spinal BMD (lumbar: r = -0.44; P = 0.06; lateral: r = -0. 59; P = 0.008). AN adolescents with mature BA (15 yr and greater) were hypo gonadal [estradiol, 16.2 +/- 1.9 vs. 23.3 +/- 1.6 pg/mL (P = 0.01); free te stosterone, 0.70 +/- 0.17 us. 1.36 +/- 0.14 pg/mL (P = 0.01)1 although dehy droepiandrosterone sulfate and urinary free cortisol levels did not differ. Leptin levels were reduced in AN (2.9 +/- 2.1 vs. 16.5 +/- 1.8 ng/mL; P < 0.0001). Insulin like growth factor I (IGF-I) was reduced in AN to 50% of c ontrol levels (219 +/- 41 vs. 511 +/- 35 ng/mL; P < 0.0001) and correlated with all measures of nutritional status, particularly leptin (r = 0.80; P < 0.0001). Surrogate markers of bone formation, serum osteocalcin (OC) and b one-specific alkaline phosphatase (BSAP), were significantly (P = 0.02) red uced in AN vs. controls (OC, 39.1 r 6.4 vs. 59.2 +/- 5.2 ng/mL; BSAP, 27.9 +/- 4.0 vs. 40.6 +/- 3.4 U/L). The majority of the variation in bone format ion in AN was due to IGF-I levels (OC: r(2) = 0.72: P = 0.002; BSAP: r(2) = 0.53; P = 0.01) in stepwise regression analyses. Bone resorption was compa rable in patients and controls. These data demonstrate that bone formation is reduced and uncoupled to bone resorption in mature adolescents with AN i n association with low bone density. Lean body mass was a significant predi ctor of BMD in controls, but not AN patients. The major correlate of bone f ormation in AN was the nutritionally dependent bone trophic factor, IGF-I. Reduced IGF-I during the critical period of bone mineral accumulation may b e an important factor in the development of osteopenia in adolescents with AN.