Top

Osteoporosis International

Published in:

01-06-2006 | Original Article

Age-related differences in hormonal and nutritional impact on lean anorexia nervosa bone turnover uncoupling

Authors: B. Galusca, C. Bossu, N. Germain, M. Kadem, D. Frere, M. H. Lafage-Proust, F. Lang, B. Estour

Published in: Osteoporosis International | Issue 6/2006

Abstract

Introduction

In anorexia nervosa (AN) patients osteoporosis occurs within a framework of multiple hormonal abnormalities as a result of bone turnover uncoupling, with decreased bone formation and increased bone resorption. The aim of study was to evaluate the hormonal and nutritional relationships with both of these bone remodeling compartments and their eventual modifications with age.

Patients and measurements

In a cohort of 115 AN patients (mean BMI:14.6 kg/m2) that included 60 mature adolescents (age: 15.5–20 years) and 55 adult women (age: 20–37 years) and in 28 age-matched controls (12 mature adolescents and 16 adults) we assessed: bone markers [serum osteocalcin, skeletal alkaline phosphatase (sALP), C-telopeptide of type I collagen (sCTX) and tartrate-resistant acid phosphatase type 5b (TRAP 5b)], nutritional markers [ body mass index (BMI, fat and lean mass), hormones (free tri-iodothyronine (T3), free T4, thyroid stimulating hormone (TSH), luteinizing hormone (LH), follicle stimulating hormone (FSH), 17 β estradiol, free testosterone index (FTI), dehydroepiandrosterone (DHEAS), insulin-like growth factor 1 (IGF-1), growth hormone (GH) and cortisol], plasma methoxyamines (metanephrine and normetanephrine) and calcium metabolism parameters [parathyroid hormone (PTH), Ca, vitamin D₃].

Results

Osteocalcin reached similar low levels in both AN age subgroups. sCTX levels were found to be elevated in all AN subjects and higher in mature adolescents than in adult AN (11,567±895 vs. 8976±805 pmol/l, p<0.05). sALP was significantly lower only in mature adolescent AN patients, while there were no significant differences in the levels of TRAP 5b between AN patients and age-matched control groups. Osteocalcin correlated with sCTX in the control subjects (r=0.65) but not in the AN patients, suggesting the independent regulation of these markers in AN patients. Osteocalcin levels strongly correlated with freeT3, IGF-I, 17 β estradiol and cortisol, while sCTX correlated with IGF-I, GH and cortisol in both age subgroups of the AN patients. Other hormones or nutritional parameters displayed age-related correlations with bone markers, leading to different stepwise regression models for each age interval. In mature adolescent AN patients, up to 54% of the osteocalcin variance was due to BMI, cortisol and 17 β estradiol, while 54% of the sCTX variance was determined by GH. In adult subjects, freeT3 and IGF-I accounted for 64% of osteocalcin variance, while 65% of the sCTX variance was due to GH, FTI and methoxyamines.

Conclusions

We suggest a more complex mechanism of AN bone uncoupling that includes not only “classical” influence elements like cortisol, IGF-I, GH or 17 β estradiol but also freeT3, catecholamines and a “direct” hormone-independent impact of denutrition. Continuous changes of these influences with age should be considered within the therapeutic approach to AN bone loss.

International Committee for Standards in Bone Measurement (1997) Standardization of proximal femur bone mineral density (BMD) measurements by DXA. Bone 21:369–370

American Psychiatric Association (1994) Diagnostic and statistical manual of mental disorders. American Psychiatric Association, D.C.

Arai M, Nagasawa T, Koshihara Y, Yamamoto S, Togari A (2003) Effects of beta-adrenergic agonists on bone-resorbing activity in human osteoclast-like cells. Biochim Biophys Acta 1640:137–142PubMedCrossRef

Audi L, Vargas DM, Gussinye 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 51:497–504PubMedCrossRef

Bartak V, Vybiral S, Papezova H, Dostalova I, Pacak K, Nedvidkova J (2004) Basal and exercise-induced sympathetic nervous activity and lipolysis in adipose tissue of patients with anorexia nervosa. Eur J Clin Invest 34:371–377PubMedCrossRef

Biller BM, Saxe V, Herzog DB, Rosenthal DI, Holzman S, Klibanski A (1989) Mechanisms of osteoporosis in adult and adolescent women with anorexia nervosa. J Clin Endocrinol Metab 68:548–554PubMed

Bonde M, Qvist P, Fledelius C, Riis BJ, Christiansen C (1995) Applications of an enzyme immunoassay for a new marker of bone resorption (CrossLaps): follow-up on hormone replacement therapy and osteoporosis risk assessment. J Clin Endocrinol Metab 80:864–868PubMedCrossRef

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 52:113–121CrossRef

Candito M, Billaud E, Chauffert M, Cottet-Emard JM, Desmoulin D, Garnier JP, Greffe J, Hirth C, Jacob N, Millot F, Nignan A, Patricot MC, Peyrin L, Plouin PF (2002) Biochemical diagnosis of pheochromocytoma and neuroblastomas. Ann Biol Clin 60:15–36

10.

Carmichael KA, Carmichael DH (1995) Bone metabolism and osteopenia in eating disorders. Medicine (Baltimore) 74:254–267CrossRef

11.

Compston JE, McConachie C, Stott C, Hannon RA, Kaptoge S, Debiram I, Love S, Jaffa A (2005) Changes in bone mineral density, body composition and biochemical markers of bone turnover during weight gain in adolescents with severe anorexia nervosa: a 1-year prospective study. Osteoporos Int 17:77–84PubMedCrossRef

12.

Eckert ED, Pomeroy C, Raymond N, Kohler PF, Thuras P, Bowers CY (1998) Leptin in anorexia nervosa. J Clin Endocrinol Metab 83:791–795PubMedCrossRef

13.

Estour B, Pugeat M, Lang F, Dechaud H, Pellet J, Rousset H (1986) Sex hormone binding globulin in women with anorexia nervosa. Clin Endocrinol (Oxf) 24:571–576

14.

Fonseca VA, D’Souza V, Houlder S, Thomas M, Wakeling A, Dandona P (1988) Vitamin D deficiency and low osteocalcin concentrations in anorexia nervosa. J Clin Pathol 41:195–197PubMedCrossRef

15.

Fuller NJ, Jebb SA, Laskey MA, Coward WA, Elia M (1992) Four-component model for the assessment of body composition in humans: comparison with alternative methods, and evaluation of the density and hydration of fat-free mass. Clin Sci 82:687–693PubMed

16.

Garnero P, Gineyts E, Riou JP, Delmas PD (1994) Assessment of bone resorption with a new marker of collagen degradation in patients with metabolic bone disease. J Clin Endocrinol Metab 79:780–785PubMedCrossRef

17.

Golden NH, Lanzkowsky L, Schebendach J, Palestro CJ, Jacobson MS, Shenker IR (2002) The effect of estrogen-progestin treatment on bone mineral density in anorexia nervosa. J Pediatr Adolesc Gynecol 15:135–143PubMedCrossRef

18.

Gordon CM, Goodman E, Emans SJ, Grace E, Becker KA, Rosen CJ, Gundberg CM, Leboff MS (2002) Physiologic regulators of bone turnover in young women with anorexia nervosa. J Pediatr 141:64–70PubMedCrossRef

19.

Gordon CM, Grace E, Emans SJ, Feldman HA, Goodman E, Becker KA, Rosen CJ, Gundberg CM, LeBoff MS (2002) Effects of oral dehydroepiandrosterone on bone density in young women with anorexia nervosa: a randomized trial. J Clin Endocrinol Metab 87:4935–4941PubMedCrossRef

20.

Goulding A, Taylor RW (1998) Plasma leptin values in relation to bone mass and density and to dynamic biochemical markers of bone resorption and formation in postmenopausal women. Calcif Tissue Int 63:456–458PubMedCrossRef

21.

Gouveia CH, Schultz JJ, Bianco AC, Brent GA (2001) Thyroid hormone stimulation of osteocalcin gene expression in ROS 17/2.8 cells is mediated by transcriptional and post-transcriptional mechanisms. J Endocrinol 170:667–675PubMedCrossRef

22.

Grinspoon S, Baum H, Lee K, Anderson E, Herzog D, Klibanski A (1996) Effects of short-term recombinant human insulin-like growth factor I administration on bone turnover in osteopenic women with anorexia nervosa. J Clin Endocrinol Metab 81:3864–3870PubMedCrossRef

23.

Grinspoon S, Thomas L, Miller K, Herzog D, Klibanski A (2002) Effects of recombinant human IGF-I and oral contraceptive administration on bone density in anorexia nervosa. J Clin Endocrinol Metab 87:2883–2891PubMedCrossRef

24.

Grinspoon SK, Baum HB, Kim V, Coggins C, Klibanski A (1995) Decreased bone formation and increased mineral dissolution during acute fasting in young women. J Clin Endocrinol Metab 80:3628–3633PubMedCrossRef

25.

Heer M, Mika C, Grzella I, Heussen N, Herpertz-Dahlmann B (2004) Bone turnover during inpatient nutritional therapy and outpatient follow-up in patients with anorexia nervosa compared with that in healthy control subjects. Am J Clin Nutr 80:774–781PubMed

26.

Hergenroeder AC (1995) Bone mineralization, hypothalamic amenorrhea, and sex steroid therapy in female adolescents and young adults. J Pediatr 126:683–689PubMedCrossRef

27.

Herpertz S, Wagner R, Albers N, Blum WF, Pelz B, Langkafel M, Kopp W, Henning A, Oberste-Berghaus C, Mann K, Senf W, Hebebrand J (1998) Circadian plasma leptin levels in patients with anorexia nervosa: relation to insulin and cortisol. Horm Res 50:197–204PubMedCrossRef

28.

Herzog W, Minne H, Deter C, Leidig G, Schellberg D, Wuster C, Gronwald R, Sarembe E, Kroger F, Bergmann G et al (1993) Outcome of bone mineral density in anorexia nervosa patients 11.7 years after first admission. J Bone Miner Res 8:597–605PubMed

29.

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 patients with anorexia nervosa. J Clin Endocrinol Metab 85:200–206PubMedCrossRef

30.

Hotta M, Shibasaki T, Sato K, Demura H (1998) The importance of body weight history in the occurrence and recovery of osteoporosis in patients with anorexia nervosa: evaluation by dual X-ray absorptiometry and bone metabolic markers. Eur J Endocrinol 139:276–283PubMedCrossRef

31.

Huang BK, Golden LA, Tarjan G, Madison LD, Stern PH (2000) Insulin-like growth factor I production is essential for anabolic effects of thyroid hormone in osteoblasts. J Bone Miner Res 15:188–197PubMedCrossRef

32.

Johansen JS, Giwercman A, Hartwell D, Nielsen CT, Price PA, Christiansen C, Skakkebaek NE (1988) Serum bone Gla-protein as a marker of bone growth in children and adolescents: correlation with age, height, serum insulin-like growth factor I, and serum testosterone. J Clin Endocrinol Metab 67:273–278PubMedCrossRef

33.

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 80:898–904PubMedCrossRef

34.

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 33:349–356PubMedCrossRef

35.

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

36.

Matkovic V, Jelic T, Wardlaw GM, Ilich JZ, Goel PK, Wright JK, Andon MB, Smith KT, Heaney RP (1994) Timing of peak bone mass in Caucasian females and its implication for the prevention of osteoporosis. Inference from a cross-sectional model. J Clin Invest 93:799–808PubMedCrossRef

37.

Mazess RB, Barden HS, Bisek JP, Hanson J (1990) Dual-energy x-ray absorptiometry for total-body and regional bone-mineral and soft-tissue composition. Am J Clin Nutr 51:1106–1112PubMed

38.

Miller KK, Grieco KA, Klibanski A (2005) Testosterone administration in women with anorexia nervosa. J Clin Endocrinol Metab 90:1428–1433PubMedCrossRef

39.

Misra M, Aggarwal A, Miller KK, Almazan C, Worley M, Soyka LA, Herzog DB, Klibanski A (2004) Effects of anorexia nervosa on clinical, hematologic, biochemical, and bone density parameters in community-dwelling adolescent girls. Pediatrics 114:1574–1583PubMedCrossRef

40.

Misra M, Miller KK, Almazan C, Ramaswamy K, Lapcharoensap W, Worley M, Neubauer G, Herzog DB, Klibanski A (2004) Alterations in cortisol secretory dynamics in adolescent girls with anorexia nervosa and effects on bone metabolism. J Clin Endocrinol Metab 89:4972–4980PubMedCrossRef

41.

Misra M, Miller KK, Bjornson J, Hackman A, Aggarwal A, Chung J, Ott M, Herzog DB, Johnson ML, Klibanski A (2003) Alterations in growth hormone secretory dynamics in adolescent girls with anorexia nervosa and effects on bone metabolism. J Clin Endocrinol Metab 88:5615–5623PubMedCrossRef

42.

Mochizuki H, Hakeda Y, Wakatsuki N, Usui N, Akashi S, Sato T, Tanaka K, Kumegawa M (1992) Insulin-like growth factor-I supports formation and activation of osteoclasts. Endocrinology 131:1075–1080PubMedCrossRef

43.

Mornex R, Peyrin L, Pagliari R, Cottet-Emard JM (1991) Measurement of plasma methoxyamines for the diagnosis of pheochromocytoma. Horm Res 36:220–226PubMedCrossRef

44.

Munoz MT, Argente J (2002) Anorexia nervosa in female adolescents: endocrine and bone mineral density disturbances. Eur J Endocrinol 147:275–286PubMedCrossRef

45.

Munoz MT, Morande G, Garcia-Centenera JA, Hervas F, Pozo J, Argente J (2002) The effects of estrogen administration on bone mineral density in adolescents with anorexia nervosa. Eur J Endocrinol 146:45–50PubMedCrossRef

46.

Nedvidkova J, Dostalova I, Bartak V, Papezov H, Pacak K (2004) Increased subcutaneous abdominal tissue norepinephrine levels in patients with anorexia nervosa: an in vivo microdialysis study. Physiol Res 53:409–413PubMed

47.

Pagliari R, Cottet-Emard JM, Peyrin L (1991) Determination of free and conjugated normetanephrine and metanephrine in human plasma by high-performance liquid chromatography with electrochemical detection. J Chromatogr 563:23–36PubMedCrossRef

48.

Pallant A, Mathian B, Prost L, Theodore C, Patricot MC (2000) Determination of plasma methoxyamines. Clin Chem Lab Med 38:513–517PubMedCrossRef

49.

Rigotti NA, Neer RM, Skates SJ, Herzog DB, Nussbaum SR (1991) The clinical course of osteoporosis in anorexia nervosa. A longitudinal study of cortical bone mass. JAMA 265:1133–1138PubMedCrossRef

50.

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

51.

Sankoh AJ, Huque MF, Dubey SD (1997) Some comments on frequently used multiple endpoint adjustment methods in clinical trials. Stat Med 16:2529–2542PubMedCrossRef

52.

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 exercise. J Bone Miner Res 7:1467–1474PubMedCrossRef

53.

Slootweg MC, Most WW, van Beek E, Schot LP, Papapoulos SE, Lowik CW (1992) Osteoclast formation together with interleukin-6 production in mouse long bones is increased by insulin-like growth factor-I. J Endocrinol 132:433–438PubMed

54.

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 84:4489–4496PubMedCrossRef

55.

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

56.

Szulc P, Seeman E, Delmas PD (2000) Biochemical measurements of bone turnover in children and adolescents. Osteoporos Int 11:281–294PubMedCrossRef

57.

Vergely N, Lafage-Proust MH, Caillot-Augusseau A, Millot L, Lang F, Estour B (2002) Hypercorticism blunts circadian variations of osteocalcin regardless of nutritional status. Bone 30:428–435PubMedCrossRef

58.

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

Title: Age-related differences in hormonal and nutritional impact on lean anorexia nervosa bone turnover uncoupling
Authors: B. Galusca
C. Bossu
N. Germain
M. Kadem
D. Frere
M. H. Lafage-Proust
F. Lang
B. Estour
Publication date: 01-06-2006
Publisher: Springer-Verlag
Published in: Osteoporosis International / Issue 6/2006
Print ISSN: 0937-941X
Electronic ISSN: 1433-2965
DOI: https://doi.org/10.1007/s00198-005-0063-0

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Age-related differences in hormonal and nutritional impact on lean anorexia nervosa bone turnover uncoupling

Abstract

Introduction

Patients and measurements

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Introduction

Patients and measurements

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 6/2006

Outcomes of a disease-management program for patients with recent osteoporotic fracture

Effects of alendronate on bone mineral density and bone metabolic markers in patients with liver transplantation

Functional outcomes of kyphoplasty for the treatment of osteoporotic and osteolytic vertebral compression fractures

Bone mineral density and estimated height loss based on patients’ recalls

Hot stuff—can’t get enough

Volumetric quantitative computed tomography of the proximal femur: relationships linking geometric and densitometric variables to bone strength. Role for compact bone