The purpose of this longitudinal study was to evaluate factors affecting changes in bone mineral density (BMD) in patients with anorexia nervosa (AN) and osteoporosis and, more particularly, to assess the benefits of hormone replacement therapy (HRT) on BMD in these patients. Our study involved 45 AN patients, 12 of whom had been treated by HRT for 2 years following a diagnosis of osteoporosis by densitometry (WHO criteria). Patients' mean age was 25.3 +/- 6.7 years. Mean duration of illness was 5.7 +/- 5.3 years. Serum calcium and phosphate were measured at baseline, as were bone remodeling markers. Osteodensitometry by dual-energy X-ray absorptiometry was performed at inclusion and after 2 years. After 2 years, no significant differences were observed between spine, femoral neck, and total hip BMDs either in the HRT group (P = 0.3, P = 0.59, P = 0.58) or in the nontreatment group (P = 0.17, P = 0.68, P = 0.98). Moreover, there were no significant differences between the two groups when changes in spine, femoral neck, and total hip BMDs at 2 years were compared (P = 0.72, P = 0.95, P = 0.58). In both groups, change in weight at 1 year correlated with change in spine BMD at 2 years (r = 0.35, P = 0.04) and change in total-hip BMD at 2 years (r = 0.35, P = 0.04) but not with change in femoral neck BMD at 2 years. Patients with a body mass index (BMI) > or = 17 kg/m(2) at 2 years showed a significant increase in total-hip BMD when compared with patients with a BMI < 17 kg/m(2) (+4.4% +/- 6.7 vs. -0.5% +/- 6.01, P = 0.03). No significant differences were observed for spine and femoral neck BMD. In patients who had recovered their menstrual cycle, significant increases were observed in spine BMD (+4% +/- 6.3 vs. -1.9% +/- 5.6, P = 0.008), femoral neck BMD (+3% +/- 6.2 vs. -2.4% +/- 8, P = 0.05), and total-hip BMD (+3% +/- 7.1 vs. -3.7% +/- 10, P = 0.04). Prevention of bone loss at 2 years in AN patients treated by HRT was not confirmed in this study. We did confirm that increase in weight at 1 year was the most predictive factor for the improvement of spine and hip BMD at 2 years.