Reprinted from Eating Disorders Review
September/October 2008 Volume 19, Number 5
©2008 Gürze Books
Loss of bone mineral density (BMD) due to malnutrition is one of the major health hazards of anorexia nervosa (AN). Until recently there were no controlled studies of bone turnover and BMD among men with AN. Results of a new study show that boys with AN have lower-than-normal BMD and decreased bone turnover, similar to that reported among girls with AN.
During adolescence, bone increases markedly due to rising levels of growth hormone (GH), insulin-like growth factor-1 (IGF-1), and gonadal steroids. Increases in GH and IGF-1 accretion lead to increases in periosteal bone apposition in early to late puberty and rising levels of gonadal steroids cause decreases in endosteal bone resorption in late puberty. Whereas estradiol is primarily anti-resorptive, testosterone has both direct bone anabolic effects and anti-resorptive effects. Conditions that lead to severe malnutrition, including AN, are associated with low IGF-1 and hypothalamic amenorrhea in females. In adolescence, boys have marked increases in lean body mass, a consistent predictor of BMD.
A small controlled study of teenaged boys
Madhusmita Misra, MD, and researchers at Massachusetts General Hospital and, Harvard Medical School, Boston, and The Hospital for Sick Children, Toronto, conducted a study among 17 adolescent boys diagnosed with AN (DSM-IV-R criteria) and 17 matched controls (J Clin Endocrinol Metab. 2008; 93:3029).
The researchers assessed BMD among both groups using dual x-ray absorptiometry (DXA), and also measured fasting testosterone, estradiol, IGF-1, leptin, ghrelin, and PYY, as well as bone desorption and bone formation markers. The boys in the study were 12 to 17 years of age, and all the controls were at least 90% of their ideal body weight.
As expected, the boys with AN had lower weight, BMI, fat and lean muscle mass than did controls. However, height and high standard deviation scores did not differ between groups. Surprisingly, compared with controls, boys with AN had higher calcium and vitamin D intake from food and supplements.
For the first time, the authors demonstrated that markers of bone turnover (markers of both formation and resorption) are reduced in boys with AN compared with controls, who are in an increased state of bone turnover. The sole significant predictor of both bone turnover markers was IGF-1, consistent with studies in girls with AN and with the known bone trophic effects.
Boys with AN had lower BMD and BMD Z-scores at the spine, hip, and of the whole body than did controls. In addition, trochanteric and intertrochanteric BMD and corresponding Z-scores were lower in boys with AN. Lower BMD was associated with reduced bone turnover state, as indicated by bone markers. Boys with the longest duration of AN since diagnosis had the lowest bone age in relation to their chronological age.
Best predictors of BMD
According to Dr. Misra and colleagues, the best predictors of BMD were testosterone levels, lean mass, BMI, and bone age. Testosterone was an important, independent predictor of spinal BMD. Testosterone levels were significantly lower among boys with AN than for control boys (186.8 ng/dL vs. 413.8 ng/dL, respectively). Among girls, the gonadal steroids and IGF-1 are key determinants of BMD, and the appetite-regulating peptides ghrelin, PYY, and leptin are important predictors of low BMD. This was not the case with the boys in the authors’ study. Ghrelin levels were not significantly higher in boys with AN, and IGF-1 did not differ between the two groups of boys.
Because boys with AN are hypogondal, and lower BMD is predicted by lower levels of testosterone, BMI and lean mass, weight recovery is critical, according to the authors.