Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Communication
  • Published:

Bone resorption in anorexia nervosa and rehabilitated patients

Abstract

Objective: To assess the impact of anorexia nervosa and that of nutritional rehabilitation on bone resorption.

Design: Cross-sectional, observational study.

Setting: Rome, Italy

Subjects: Twenty-eight female patients affected by anorexia nervosa (AN, BMI≤17.0 kg/m2), 18 females rehabilitated from anorexia nervosa and weight-stable for at least 6 months (RE, BMI ≥18.5 kg/m2) and 34 age- and sex-matched healthy controls (CO, BMI ≥18.5 kg/m2). Among AN patients, 16 were affected by the ‘restrictive’ (ANr) and 12 by the ‘purging’ type (ANp) of anorexia nervosa.

Methods: Body weight, height and skeletal diameters were measured on each individual. The skeletal mass (SKM) was predicted from the skeletal diameters of the elbow, wrist, knee and ankle, using the equation of Martin. Twenty-four-hour urinary excretion of pyridinium crosslinks of collagen (pyridinoline (Pyd) and deoxypyridinoline (Dpd)) and creatinine was assessed by reversed-phase HPLC with fluorimetric detection after solid-phase extraction and by the Jaffé-method with deproteinization, respectively.

Results: Twenty-four-hour urinary output of Pyd and Dpd was not significantly different between AN and CO when expressed in absolute values, but AN showed higher bone resorption than CO when Pyd and Dpd excretion was adjusted by either creatinine (P<0.0000) or the SKM (P<0.05). Within the AN group, urinary excretion of both cross-links was significantly and consistently higher in ANp compared with ANr (P<0.05). However, these differences disappeared when crosslink output was adjusted either by urinary creatinine or SKM. RE subjects showed no differences in bone resorption with the AN group despite weight gain, being crosslink excretion consistently elevated compared to controls (Pyd: P<0.01 by creatinine and P<0.05 by SKM; Dpd: P<0.01 by creatinine and P<0.05 by SKM).

Conclusion: Bone resorption is elevated in anorexia nervosa and different strategies for low-weight maintenance do not seem to have a differential impact. Increased bone resorption persists in subjects with past diagnosis of anorexia nervosa despite rehabilitation lasting more than 6 months. This finding indicates that bone mass and turnover should be monitored in anorexia nervosa patients and ex-patients well beyond recovery of normal body mass. Further investigation is warranted to examine the long-term effect of such prolonged increase in bone turnover at a young age.

Sponsorship: Dr. Valtueña is supported by a Marie Curie Fellowship from the European Commission (Contact no. HPMF-CT-1999-00192).

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

Notes

  1. Whole body-DXA scans (model Hologic, QDR-4500W, Lincoln St. Walthman, Mass) were performed according to a previously published procedure (Fabbri et al, 1999)

References

  • American Psychiatric Association (1994). Diagnostic and Statistical Manual of Mental Disorders, 4th edn. Washington, DC

  • Andersen, AE, Woodward, PJ & LaFrance, N (1995). Bone mineral density of eating disorder subgroups. Int. J. Eat. Disord., 18, 335–342.

    Article  CAS  Google Scholar 

  • Bachrach, LK, Guido, D, Katzman, D, Litt, IF & Marcus, R (1990). Decreased bone density in adolescent girls with anorexia nervosa. Pediatrics, 86, 440–447.

    CAS  PubMed  Google Scholar 

  • Baker, D, Roberts, R & Towell, T (2000). Factors predictive of bone mineral density in eating-disordered women: a longitudinal study. Int. J. Eat. Disord, 27, 29–35.

    Article  CAS  Google Scholar 

  • Branca, F, Valtueña, S, Golden, M & Robins, S (2002). Urinary collagen cross-links as biochemical markers of growth: an evaluation of biological variables. Ann. Nutr. Metab., 46, 80–87.

    Article  CAS  Google Scholar 

  • Caillot-Augusseau, A, Lafage-Proust, MH, Margaillan, P, Vergely, N, Faure, S, Paillet, S, Lang, F, Alexandre, C & Estour, B (2000). Weight gain reverses bone turnover and restores circadian variation of bone resorption in anorexic patients. Clin. Endocrinol. (Oxf.), 52, 113–121.

    Article  CAS  Google Scholar 

  • Castro, J, Lazaro, L, Pons, F, Halperin, I & Toro, J (2000). Predictors of bone mineral density reduction in adolescents with anorexia nervosa. J. Am. Acad. Child Adolesc. Psychiatr., 39, 1365–1370.

    Article  CAS  Google Scholar 

  • de la Piedra, C, Calero, JA, Traba, ML, Asensio, MD, Argente, J & Muñoz, MT (1999). Urinary alpha and beta C-telopeptides of collagen I: clinical implications in bone remodeling in patients with anorexia nervosa. Osteoporos. Int., 10, 480–486.

    Article  CAS  Google Scholar 

  • Fincato, G, Barticci, F, Rigoldi, M, Abbiati, G, Colombo, M, Bartolini, O, Brandi, M & De Leonardis, V (1993). Urinary excretion of pyridiniline and deoxypyridinoline: circadian rhythm in healthy premenopausal women. J. Interdiscpl. Cycle Res., 24, 72–78.

    Article  CAS  Google Scholar 

  • Garnero, P, Hausherr, E, Chapuy, M, Marcelli, C, Grandjean, H, Muller, C, Cormier, C, Breart, G, Meunier, P & Delmas, P (1996a). Markers of bone resorption predict hip fracture in elderly women: The EPIDOS prospective study. J. Bone Miner. Res., 11, 1531–1538.

    Article  CAS  Google Scholar 

  • Garnero, P, Sornay-Rendu, E, Chapuy, M & Delmas, P (1996b). Increased bone turnover in late postmenopausal women is a major determinant of osteoporosis. J. Bone Miner. Res., 11, 337–349.

    Article  CAS  Google Scholar 

  • Garnero, P, SornayRendu, E, Duboeuf, F & Delmas, P (1999). Markers of bone turnover predict postmenopausal forearm bone loss over 4 y: the OFELY study. J. Bone Miner. Res., 14, 1614–1621.

    Article  CAS  Google Scholar 

  • Goldhaber, P & Rabadjija, L (1987). H+ stimulation of cell-mediated bone resorption in tissue culture. Am. J. Physiol., 253, E90–98.

    Article  CAS  Google Scholar 

  • Hotta, M, Fukuda, I, Sato, K, Hizuka, N, Shibasaki, T & Takano, K (2000). The relationship between bone turnover and body weight, serum insuline-like growth factor (IGF) I, and serum IGF-binding protein levels in patients with anorexia nervosa. J. Clin. Endocrinol. Metab., 85, 200–206.

    CAS  PubMed  Google Scholar 

  • Jagielska, G, Wolańczky, T, Komender, J, Tomaszewicz-Libudzic, C, Przedlacki, J & Ostrowski, K (2001). Bone mineral content and bone mineral density in adolescent girls with anorexia nervosa-a longitudinal study. Acta Phychiatr. Scand., 104, 131–137.

    Article  CAS  Google Scholar 

  • Kehayias, JJ & Valtueña, S (1999). Neutron activation analysis determination of body composition. Curr. Opin. Clin. Nutr. Metab. Care, 2, 453–463.

    Article  CAS  Google Scholar 

  • 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, 349–356.

    Article  CAS  Google Scholar 

  • Lohman, TC, Roche, AF & Martorell, R (1988). Antropometric Standardization Reference Manual, Chicago, IL: Human Kinetics

    Google Scholar 

  • Lucas, AR, Melton, LJ, Crowson, CS & O'Fallon, WM (1999). Long-term fracture risk among women with anorexia nervosa: a population-based cohort study. Mayo Clin. Proc., 74, 972–977.

    Article  CAS  Google Scholar 

  • Marowska, J, Kobylinska, M, Ukaszkiewicz, J, Taajko, A, Rymkiewicz-Kluczynska, B & Lorenc, R (1996). Pyridinium crosslinks of collagen as a marker of bone resorption rates in children and adolescents: normal values and clinical application. Bone, 19, 669–677.

    Article  CAS  Google Scholar 

  • Martin, AD (1991). Antropometric assessment of bone mineral. In:Antropometric Assessment of Nutritional Status, ed. JH Himes, pp184–196, Minneapolis, MN: Wiley-Liss

    Google Scholar 

  • McLaren, A, Isdale, A, Whitings, P, Bird, H & Robins, S (1993). Physiological variations in the urinary excretion of pyridinium crosslinks of collagen. Br. J. Rheumatol., 32, 307–312.

    Article  CAS  Google Scholar 

  • Polito, A, Cuzzolaro, M, Raguzzini, A, Censi, L & Ferro-Luzzi, A (1998). Body composition changes in anorexia nervosa. Eur. J. Clin. Nutr., 52, 655–662.

    Article  CAS  Google Scholar 

  • Polito, A, Fabbri, A, Ferro-Luzzi, A, Cuzzolaro, M, Censi, L, Ciarapica, D, Fabbrini, E & Giannini, D (2000). Basal metabolic rate in anorexia nervosa: relation to body composition and leptin concentrations. Am. J. Clin. Nutr., 71, 1495–1502.

    Article  CAS  Google Scholar 

  • Pratt, DA, Daniloff, Y, Duncan, A & Robins, SP (1992). Automated analysis of the pyridinium crosslinks of collagen in tissue and urine using solid-phase extraction and reversed-phase high-performance liquid chromatography. Anal. Biochem., 207, 168–175.

    Article  CAS  Google Scholar 

  • Rauch, F, Rauch, R, Woitge, H, Seibel, M & Schonau, E (1996). Urinary immunoreactive deoxypyridinoline in children and adolescents: variations with age, sex and growth velocity. Scand. J. Clin. Lab. Invest., 56, 715–719.

    Article  CAS  Google Scholar 

  • Rigotti, NA, Nussbaum, SR, Herzog, DB & Neer, RM (1984). Osteoporosis in women with anorexia nervosa. New Engl. J. Med., 311, 1601–1606.

    Article  CAS  Google Scholar 

  • 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, 4489–4496.

    CAS  PubMed  Google Scholar 

  • Spierto, FW, MacNeil, ML & Burtis, CA (1979). The effect of temperature and wavelength on the measurement of creatinine with the Jaffè procedure. Clin. Biochem., 12, 18–21.

    Article  CAS  Google Scholar 

  • Stefanis, N, Mackintosh, C, Abraha, HD, Treasure, J & Moniz, C (1998). Dissociation of bone turnover in anorexia nervosa. Ann. Clin. Biochem., 35, 709–716.

    Article  Google Scholar 

  • Valla, A, Groenning, IL, Syversen, U & Hoeiseth, A (2000). Anorexia nervosa: slow regain of bone mass. Osteoporos. Int., 11, 141–145.

    Article  CAS  Google Scholar 

  • Valtueña, S, Sette, S & Branca, F (2001). Influence of Mediterranean diet and Mediterranean lifestyle on calcium and bone metabolism. Int. J. Vit. Nutr. Res., 71, 189–202.

    Article  Google Scholar 

  • Vesper, HW, Demers, LM, Eastell, R, Garnero, P, Kleerekoper, M, Robins, SP, Srivastava, AK, Warnick, GR, Watts, NB & Myers, GL (2002). Assessment and recommendation on factors contributing to variability of preanalytical urinary pyridinoline and deoxypyridinoline. Clin. Chem., 48, 220–235.

    CAS  PubMed  Google Scholar 

  • Wachman, A & Bernstein, DS (1968). Diet and osteoporosis. Lancet, 1, 958–959.

    Article  CAS  Google Scholar 

  • Ward, A, Brown, N & Treasure, J (1997). Persistent osteopenia after recovery from anorexia nervosa. Int. J. Eat. Disord., 22, 71–75.

    Article  CAS  Google Scholar 

  • Zipfel, S, Seibel, MJ, Löwe, 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, 5227–5233.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We would like to thank Donatella Ciarapica for her help in performing the 24 h urine collections, subject recruitment and anthropometric measurements.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to F Branca.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Valtueña, S., Di Mattei, V., Rossi, L. et al. Bone resorption in anorexia nervosa and rehabilitated patients. Eur J Clin Nutr 57, 260–265 (2003). https://doi.org/10.1038/sj.ejcn.1601527

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.ejcn.1601527

Keywords

This article is cited by

Search

Quick links