Calcified Tissue International

, Volume 81, Issue 3, pp 174–182 | Cite as

Evaluation of Bone Loss and Its Mechanisms in Anorexia Nervosa

  • Isabelle Legroux-GérotEmail author
  • Jean Vignau
  • Michèle D’Herbomez
  • Francis Collier
  • Xavier Marchandise
  • Bernard Duquesnoy
  • Bernard Cortet


The purpose of this cross-sectional study was to assess the extent of and mechanisms involved in bone loss in anorexia nervosa patients. We compared 113 anorexia nervosa patients (mean age 25 ± 8 years, mean duration of disease 5.7 ± 6.1 years) with 21 age-matched controls. Mean duration of amenorrhea was 3.2 ± 4.7 years. We measured serum calcium and phosphate; bone remodeling markers (osteocalcin, bone-specific alkaline phosphatase [BSAP], serum crosslaps [CTX], and carboxyl-terminal telopeptide of type I collagen [ICTP]); follicle-stimulating hormone and luteinizing hormone levels; and estradiol (ultrasensitive assay), cortisol, urinary free cortisol, thyroid function, prolactin, and nutritional factors (insulin-like growth factor I [IGF-I], IGF binding protein 3 [IGFBP3]). In controls, only bone remodeling markers and nutritional factors were measured. Osteodensitometry was also performed on both patients and controls. Weight and body mass index (BMI) were significantly lower in anorexia nervosa patients than in controls (P < 0.0001). No significant differences were observed in biological indicators except for IGF-I, which was lower in anorexia nervosa patients (0.9 ± 0.4 UI/mL) than in controls (1.5 ± 0.4 UI/mL) (P < 0.0001). Densitometric measurements at three sites were significantly lower in anorexia nervosa patients and correlated with duration of disease and amenorrhea and with IGF-I at the hip only (P < 0.01). In the study population, osteoporosis was observed in 24 patients (21%) and osteopenia in 54 patients (48%). Patients with osteoporosis were significantly older and had longer disease and amenorrhea durations; lower weight and BMI; higher alkaline phosphatase, BSAP, and osteocalcin; and lower serum ICTP, IGF-I, and IGFBP3. All of these differences were significant and remained so even after multiple adjustments were made, except for IGF-I (P = 0.21). When multivariate analysis was performed, we found that age at onset of amenorrhea, weight, alkaline phosphatase, urinary free cortisol, and serum estradiol concentration accounted for 54% of the variance in spinal bone mineral density (BMD). Duration of amenorrhea, alkaline phosphatase, and weight explained 46.6% of the variance in femoral neck BMD. Duration of amenorrhea, IGF-I, and ICTP levels accounted for 38.6% of the variance observed in total hip BMD. The etiology of bone loss in patients with anorexia nervosa is multifactorial. Hypoestrogenia alone cannot account for this loss, and nutritional factors, IGF-I concentrations in particular, seem to play an important role.


Anorexia nervosa Osteoporosis Osteodensitometry 


  1. 1.
    Munoz MT, Argente J (2002) Anorexia nervosa in female adolescents : endocrine and bone mineral density disturbances. Eur J Endocrinol 147:275–286PubMedCrossRefGoogle Scholar
  2. 2.
    Hsu LK (1996) Epidemiology of eating disorders. Psychiatr Clin North Am 19:681–760PubMedCrossRefGoogle Scholar
  3. 3.
    Herzog W, Minne H, Deter C, Leiding G, Schellberg D, Wuster C, et al. (1993) Outcome of bone mineral density in anorexia nervosa patients 11.7 years after first admission. J Bone Miner Res 8:597–605PubMedCrossRefGoogle Scholar
  4. 4.
    Zipfel S, Beumont PJ, Russel J, Herzog W (2000) Osteoporosis in eating disorders. Eur Eat Disord Rev 8:108–116CrossRefGoogle Scholar
  5. 5.
    Grinspoon S, Thomas E, Pitts S, Gross E, Mickley D, Miller K, et al. (2000) Prevalence and predictive factors for regional osteoporosis in women with anorexia nervosa. Ann Intern Med 133:790–794PubMedGoogle Scholar
  6. 6.
    Bachrach LK, Katzman DK, Litt IF, Guido D, Marcus R (1991) Recovery from osteopenia in adolescent girls with anorexia nervosa. J Clin Endocrinol Metab 72:602–606PubMedCrossRefGoogle Scholar
  7. 7.
    Soyka LA, Grinspoon S, Levitsky LL, Herzog DB, Klibanski A (1999) The effects of anorexia nervosa on bone metabolism in female adolescents. J Clin Endocrinol Metab 84:4489–4496PubMedCrossRefGoogle Scholar
  8. 8.
    Zipfel S, Seibel MJ, Lowe B, Beumont PJ, Kasperk C, Herzog W (2001) Osteoporosis in eating disorders: a follow-up study of patients with anorexia and bulimia nervosa. J Clin Endocrinol Metab 86:5227–5233PubMedCrossRefGoogle Scholar
  9. 9.
    Brotman AW, Stern TA (1985) Osteoporosis and pathologic fractures in anorexia nervosa. Am J Psychiatry 142:495–496PubMedGoogle Scholar
  10. 10.
    Maugars Y, Clochon P, Grardel B, Hary S, Phelip X, Forestier R, et al. (1991) Etude du retentissement osseux dans 33 cas d’anorexie mentale dont 8 avec une ostéoporose fracturaire. Rev Rhum Mal Osteoarthritis 58:751–758Google Scholar
  11. 11.
    Herzog W, Deter HC, Fiehn W, Petzold E (1997) Medical findings and predictors of long-term physical outcome in anorexia nervosa: a prospective, 12-year follow-up study. Psychol Med 27:269–279PubMedCrossRefGoogle Scholar
  12. 12.
    Grinspoon S, Miller K, Coyle C, Krempin J, Armstrong C, Pitts S, Herzog D, Klibanski A (1999) Severity of osteopenia in oestrogen-deficient women with anorexia nervosa and hypothalamic amenorrhea. J Clin Endocrinol Metab 84:2049–2055PubMedCrossRefGoogle Scholar
  13. 13.
    Jacoangeli F, Zoli A, Taranto A, Staar Mezzasalma F, Ficoneri C, Pierangeli S, et al. (2002) Osteoporosis and anorexia nervosa: relative role of endocrine alterations and malnutrition. Eat Weight Disord 7:190–195PubMedGoogle Scholar
  14. 14.
    Bachrach LK, Guido D, Katzman D, Litt IF, Marcus R (1990) Decreased bone density in adolescent girls with anorexia nervosa. Pediatrics 86:440–447PubMedGoogle Scholar
  15. 15.
    Fardellone P, Sebert JL, Bouraya M, Bonidan O, Leclercq G, Doutrellot C, Bellony R, Dubreuil A (1991) Evaluation of the calcium content of diet by frequential self-questionnaire. Rev Rhum Engl Ed 58:99–103Google Scholar
  16. 16.
    Silman AJ, O’Neill TW, Cooper C, Kanis J, Felsenberg D, European Vertebral Osteoprosis Study Group (1997) Influence of physical activity on vertebral deformity in men and women: results from the European Vertebral Osteoporosis Study. J Bone Miner Res 12:813–819PubMedCrossRefGoogle Scholar
  17. 17.
    Lennkh C, De Zwaan M, Bailer U, Strnad A, Nagy C, El-Giamal N, Wiesnagrotzki S, Vytiska E, Huber J, Kasper S (1999) Osteopenia in anorexia nervosa: specific mechanisms of bone loss. J Psychiatr Res 33:349–356PubMedCrossRefGoogle Scholar
  18. 18.
    Stefanis N, Mackintosh C, Abraha HD, Treasure J, Moniz C (1998) Dissociation of bone turnover in anorexia nervosa. Ann Clin Biochem 35:709–716PubMedGoogle Scholar
  19. 19.
    Bolton JGF, Patel S (2001) Osteoporosis in anorexia nervosa. J Psychosom Res 50:177–178PubMedCrossRefGoogle Scholar
  20. 20.
    Audi L, Vargas DM, Gussinyé M, Yeste D, Marti G, Carrascosa A (2002) Clinical and biochemical determinants of bone metabolism and bone mass in adolescent female patients with anorexia nervosa. Pediatr Res 51:497–504PubMedCrossRefGoogle Scholar
  21. 21.
    White CM, Hergenroeder AC, Klish WJ (1992) Bone mineral density in 15–21 year old eumenorrheic subjects. Am J Dis Child 146:31–35PubMedGoogle Scholar
  22. 22.
    Hergenroeder AC (1995) Bone mineralization, hypothalamic amenorrhea, and sex steroid therapy in female adolezscents and young adults. J Pediatr 126:683–689PubMedCrossRefGoogle Scholar
  23. 23.
    Seeman E, Szmukler GI, Formica C, Tsalamandris C, Mestrovic R (1992) Osteoporosis in anorexia nervosa: the influence of peak bone density, bone loss, oral contraceptive use, and exercice. J Bone Miner Res 7:1467–1474PubMedGoogle Scholar
  24. 24.
    Klibanski A, Biller BM, Schoenfeld DA, Herzog DB, Saxe VC (1995) The effects of estrogen administration on trabecular bone loss in young women with anorexia nervosa. J Clin Endocrinol Metab 80:898–904PubMedCrossRefGoogle Scholar
  25. 25.
    Golden NH, Lanzkowsky L, Schebendach J, Palestro CJ, Jacobson MS, Shenker R (2002) The effect of estrogen-progestin treatment on mineral density in anorexia nervosa. J Pediatr Adolesc Gynecol 15:135–143PubMedCrossRefGoogle Scholar
  26. 26.
    Valla A, Groenning IL, Syversen U, Hoeiseth A (2000) Anorexia nervosa: slow regain of bone mass. Osteoporos Int 11:141–145PubMedCrossRefGoogle Scholar
  27. 27.
    Tomten SE, Falch JA, Birkeland KI, Hemmersbach P, Hostmark AT (1998) Bone mineral density and menstrual irregularities. A comparative study on cortical and trabecular bone structures in runners with alleged normal eating behavior. Int J Sports Med 19:92–97PubMedCrossRefGoogle Scholar
  28. 28.
    Grinspoon SK, Friedman AJ, Miller KK, Lippman J, Olson WH, Warren MP (2003) Effects of a triphasic combination oral contraceptive containing norgestimate/ethinyl estradiol on biochemical markers of bone metabolism in young women with osteopenia secondary to hypothalamic amenorrhea. J Clin Endocrinol Metab 88:3651–3656PubMedCrossRefGoogle Scholar
  29. 29.
    Sun L, Zhang Z, Peng Y, Iqbal J, Zaidi S, Papachristou DJ, Zhou H (2005) FSH directly regulates bone mass: implications for understanding the pathogenesis of osteoporosis due to hypogonadism. J Bone Miner Res 20:1043 (abstract)CrossRefGoogle Scholar
  30. 30.
    Counts DR, Gwirtsman H, Carlsson LMS, Lesem M, Cutler GB Jr (1992) The effect of anorexia nervosa and refeeding on growth hormone-binding protein, the insulin-like growth factor (IGFs), and the IGF-binding proteins. J Clin Endocrinol Metab 75:762–767PubMedCrossRefGoogle Scholar
  31. 31.
    Golden NH, Kreitzer P, Jacobson MS, Chasalow FI, Schebendach J, Freedman SM, et al. (1994) Disturbances in growth hormone secretion and action in adolescents with anorexia nervosa. J Pediatr 125:655–660PubMedCrossRefGoogle Scholar
  32. 32.
    Argente J, Munoz MT, Pozo J, Barrios V, Buno M, Chowen JA, et al. (1998) Growth hormone resistance in anorexia nervosa as a model of malnutrition. J Endocrinol Invest 21:24–28Google Scholar
  33. 33.
    Hotta M, Fukuda I, Sato K, Hizuka N, Shibasaki T, Takano K (2000) The relationship between bone turnover and body weight, serum insulin-like growth factor (IGF) I, and serum IGF-binding protein levels in patient with anorexia nervosa. J Clin Endocrinol Metab 85:200–206PubMedCrossRefGoogle Scholar
  34. 34.
    Soyka LA, Misra M, Frenchman A, Miller K, Grinspoon S, Schoenfeld DA, Klibanski A (2002) Abnormal bone mineral accrual in adolescent girls with anorexia nervosa. J Clin Endocrinol Metab 87:4177–4185PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Isabelle Legroux-Gérot
    • 1
    Email author
  • Jean Vignau
    • 2
  • Michèle D’Herbomez
    • 3
  • Francis Collier
    • 4
  • Xavier Marchandise
    • 3
  • Bernard Duquesnoy
    • 1
  • Bernard Cortet
    • 1
  1. 1.Department of RheumatologyUniversity Hospital of Lille, Hôpital Roger SalengroLille cédexFrance
  2. 2.Department of AddictologyUniversity Hospital of Lille, Hôpital La CharitéLille cédexFrance
  3. 3.Department of Nuclear MedicineUniversity Hospital of Lille, Hôpital Roger SalengroLille cédexFrance
  4. 4.Department of GynecologyUniversity Hospital of Lille, Hôpital Jeanne de FlandreLille cédexFrance

Personalised recommendations