Weight gain reverses bone turnover and restores circadian variation of bone resorption in anorexic patients

OBJECTIVE The present study was conducted in order to describe the variatio ns and circadian rhythm of biochemical markers of bone remodelling at basel ine and after weight gain in patients with aneroxia nervosa (AN). SUBJECTS We studied 9 women (mean age 21 years, range: 16-30) with establis hed AN who remained amenorrhoeic during the study and with a low body mass index (BMI) after refeeding and 6 female controls (mean age 20 years, range , 18-24 and BMI: 20.6 +/- 1.1 kg/m(2)). Refeeding was not associated with a ny other intervention or treatment, especially oestrogen replacement or hor monal contraception. Serum levels of oestradiol remained below 70 pmol/l be fore and after refeeding. MEASUREMENTS During the study, PTH and 25-hydroxyvitamin D measurements wer e performed. Markers of bone formation: serum intact osteocalcin (iBGP) and serum intact BGP + fragments (iBGP+F) and markers of bone resorption: urin e C-teloptide of type I collagen (uCTX) and serum C-telopeptide ofv-type 1 collagen (s-CTX) were measured. RESULTS At baseline, PTH and 25 OH-vitamin D concentrations were within the normal range in AN patients and no significant variation was observed afte r refeeding. Bone formation markers were found to be significantly differen t at baseline between AN patients and controls. After refeeding, iBGP and i BGP+F levels increased by 172% and 154%, respectively, to values no differe nt from controls. Intact BGP and iBGP+F exhibited a significant circadian v ariation in controls (P < 0.05 and P < 0.002, respectively), whereas we did not find any such circadian rhythm in AN patients. After refeeding no sign ificant circadian variation was observed; however, iGBP+F tended to peak in early morning and exhibited a nadir in the afternoon. At baseline, sCTX wa s 2-fold higher in AN patients than in controls. After weight gain sCTX dec reased significantly and reached control values. Refeeding induced a non-si gnificant 40% decrease in uCTX. We found positive correlations between uCTX and the 24-h mean value of sCTX levels (r(2) = 0.93, P < 0.0001) and betwe en uCTX and the mean value of sCTX peak levels at 0800 h (r(2) = 0.65, P < 0.0003). Serum CTX exhibited a significant circadian variation in controls (P < 0.001) with a peak at 0800 h and a nadir at 1600 h with a 60% decrease between peak and nadir values. We found that anorexia nervosa suppressed t he sCTX circadian variation which was restored by refeeding. We found a sig nificant non-linear relationship between BMI and sCTX/iBGP ratio in AN (r(2 ) = 0.6, P < 0.0001), thus illustrating the influence of nutritional status on bone remodelling. CONCLUSIONS In this study we found that weight gain, related to refeeding o nly, reversed the anorexia nervosa-induced uncoupling of bone remodelling a nd restored circadian variation of a bone resorption marker.