Anorexia nervosa (AN) is a condition of self-induced weight loss, associated with an intense fear of gaining weight. Previous studies have shown that bone density may increase with regaining and maintaining normal weight; however, relatively little is known about the changes in bone metabolism that occur during weight restoration. We describe the effect of weight restoration and maintenance of weight over 1 year on bone mineral density (BMD) and bone turnover. We recruited women from the eating disorders services at the South West London and St George's Mental Health NHS Trust, and the Priory and Charter Nightingale Hospitals in London, UK. Details of their AN, fracture history, menstrual history and exercise were obtained by interview and case note review. Morning samples of blood and second void urine were taken for biochemical analysis. BMD was measured by DXA at the lumbar spine (LS), femoral neck (FN), distal radius (RD) and total body bone mineral content (BMC). Patients then entered the treatment program, which includes re-feeding, dietary education and psychotherapy. Over a period of 42 months, we recruited 55 women who agreed to participate in this study and underwent baseline investigations. Of these, 15 (27%) subjects achieved and then maintained their target weight for the duration of the study. At baseline for all subjects (n=55) estradiol levels were lower than the normal reference ranges (both follicular and luteal phases) in 91% of the women. Bone specific alkaline phosphatase (BSAP) concentrations were lower than the premenopausal reference range in 55% of women, and urinary deoxypyridinoline (DPD) was above the premenopausal reference range in 78% of women. Baseline lumbar spine BMD was positively related to BMI (Pearson's r=0.29, P=0.04) and inversely related to bone turnover markers: urinary DPD (Pearson's r=-0.39, P=0.01 and serum BSAP (Pearson's r=-0.3, P=0.06). The 15 patients who regained and maintained weight were followed-up for a mean duration of 69 weeks (SD 7.3, range 54 to 84 weeks). Mean BMI increased from 14.2 (1.7) to 20.2 (0.77) kg/m2 and remained stable throughout follow-up. Menstruation resumed in 8 of the 15 women. Total body BMC and LS BMD increased significantly over the duration of follow-up (by 4.3% each), but FN BMD and distal radius remained stable. Lumbar spine bone area also increased significantly, whereas FN and distal radius did not. These changes were associated with a significant increase in BSAP (P=0.01), and a non-significant trend for a decrease in DPD (P=0.10). Our findings suggest that when women are at low body weight they are in a hypo-estrogenic state, which is associated with imbalance of bone turnover (high bone resorption and low bone formation). This is reversed with weight gain and persists as target weight is maintained and is associated with increases in BMC and BMD.