Mechanisms of Osteoporosis in Adult and Adolescent Women with Anorexia Nervosa*

Abstract

Osteoporosis is a known consequence of anorexia nervosa (AN) in adults, but the mechanism of bone loss is not established, and there have been no studies of bone mass in women developing AN before attaining peak bone mass. To investigate the causes of bone loss in AN and to determine the consequences of developing AN during adolescence on bone mass, we compared the effects of AN on cortical and trabecular bone in 26 women with AN (19 adults, 18-42 yr old, and 7 adolescents, 14.9-17.0 yr old) using direct radial photon absorptiometry and both single and dual energy spinal computed tomography. The adult AN patients had marked spinal osteopenia [mean bone density, 120 +/- 28 (+/- SD) mg K2HPO4/cm3] compared with age-matched normal women (mean, 176 +/- 26 mg K2HPO4/cm3; P = 0.0001), which was severe (greater than 2 SD below the normal mean) in 50% of patients. Adult AN patients with the onset of amenorrhea before age 18 yr had significantly (P = 0.04) lower spinal bone density than those developing amenorrhea later (mean, 103 +/- 25 vs. 129 +/- 25 mg K2HPO4/cm3) independent of other variables correlated with bone density (duration of amenorrhea or urinary cortisol excretion). We found a negative correlation between spinal bone density and duration of amenorrhea (P = 0.006; r = -0.53). To determine the contribution of endogenous cortisol excess to the pathogenesis of the osteoporosis, urinary cortisol was measured. Urinary cortisol/creatinine clearance was significantly (P = 0.001) higher in AN patients than in normal women (mean, 2.7 +/- 1.2 vs. 1.0 +/- 0.3 nmol/L) and was negatively correlated (P = 0.03; r = -0.43) with bone mass. We conclude that AN affects trabecular bone and that both the onset of AN before attainment of peak bone mass and prolonged duration of amenorrhea result in more severe osteopenia. In addition to the significant contribution of hypogonadism, the cortisol excess that occurs in AN patients may contribute to the development of osteoporosis in these patients.

Body composition changes in anorexia nervosa

“…A very diverse degree and pattern of bone mineral density reduction in anorexia has been reported in various studies and there does not appear to exist a consensus (Rigotti et al, 1984(Rigotti et al, , 1991Seeman et al, 1992;Herzog et al, 1993). Lumbar BMD tended to be more reduced than distal radial BMD (Biller et al, 1989;Davies et al, 1990;Joyce et al, 1990). This might be explained by the fact that the skeleton is not a single functioning entity and several factors as hormonal de®ciency and excess, drug therapy and physical activity might participate in improving or accelerating osteoporosis in anorexia (Seeman et al, 1992;Rigotti et al, 1984).…”

“…The skeleton is relatively spared thus becoming a larger proportion of the lean body mass (Hannan et al, 1990). However, there is some evidence that bone might be compromised in anorexia as a consequence of nutrition deprivation, cortisol elevation and hypoestrogenia (Rigotti et al, 1984;Biller et al, 1989;Davies et al, 1990;Herzog et al, 1993).…”

Body mass index and disease duration are predictors of disturbed bone turnover in anorexia nervosa. A case–control study

“…The prevalence rate is 0.2-1.0% in Western countries (Hsu, 1996;Wakeling, 1996). Severe osteopenia and clinical fractures are frequent complications (Biller et al, 1989;LaBan et al, 1995;Maugars et al, 1996). The pathogenesis of osteoporosis in AN, however, has not been completely characterized.…”

“…The pathogenesis of osteoporosis in AN, however, has not been completely characterized. Nutritional factors such as low body mass index (BMI) (Bachrach et al, 1990) and hormonal factors such as reduced sex hormone levels (Biller et al, 1989), and increased levels of glucocorticoids (Biller et al, 1989) may contribute to the low bone mineral density of AN patients. Moreover, some prospective short-term studies indicate an increased bone formation after weight gain (Stefanis et al, 1998;Heer et al, 2002).…”

The effects of bone therapy on tibial bone loss in young women with anorexia nervosa

“…The cause of decreased bone mineral density (BMD) in patients with AN is controversial. Weight loss, estrogen deficiency, malnutrition, glucocorticoid excess, and shortage of calcium and vitamin D intake are all implicated to some degree (Bachrach, Guido, Katzman, Litt, & Marcus, 1990;Biller et al, 1989;Newman & Halmi, 1989). In a longitudinal study, osteopenia in AN was not attributable merely to weight loss (Ruegsegger et al, 1988).…”