Decreased osteoprotegerin and increased bone turnover in young female patients with major depressive disorder and a lifetime history of anorexia nervosa
Abstract
Low bone mineral density (BMD) is a frequent, often persistent complication in patients with major depressive disorder (MDD) and anorexia nervosa (AN) that increases the risk of pathologic fractures. The pathogenetic process underlying osteopenia in MDD and AN is still unclear, although several factors, including a dysbalance of cytokines, are associated with loss of bone mass. Alterations in the serum levels of cytokines have been observed in patients with MDD, AN, and other psychiatric disorders. Therefore, we examined serum levels of cytokines, markers of bone turnover, and BMD in 13 patients with MDD and a lifetime history of AN. Bone turnover markers (osteocalcin and C-terminal degradation products of type I collagen) and tumor necrosis factor alpha (TNF-alpha) in patients were significantly increased compared with those of the control group. Osteoprotegerin (OPG) in patients was significantly decreased. Eight of 13 patients (62%) displayed osteopenia at the lumbar spine. TNF-alpha correlated significantly with C-terminal degradation products of type I collagen, an osteoclastic marker, but significantly negatively with OPG. Our data suggest that TNF-alpha and OPG may play a role in the pathogenetic process underlying osteopenia in these patients.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Although the association between depression and loss of bone mineral density has been reported inconsistently, most studies have found low bone mineral density in patients with depressive symptoms or major depressive disorder.
“Although the association between depression and loss of BMD has been reported inconsistently, most studies have found low BMD in patients with depressive symptoms or major depressive disorder (477-483).”
From Physical illness in patients with severe mental disorders. I. Prevalence, impact of medications and disparities in health care (2011) · cites this paper as [480]
Cites
Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation.
Lacey, D. L., Timms, E., Tan, H.-L., Kelley, M. J., Dunstan, C. R., Burgess, T., Elliott, R., Colombero, A., Elliott, G., Scully, S., et al. (1998) · Cell · doi:10.1016/s0092-8674(00)81569-x · Cited by 5,439 · see citing works
ASSESSMENT OF FRACTURE RISK AND ITS APPLICATION TO SCREENING FOR POSTMENOPAUSAL OSTEOPOROSIS
Alexeeva, L. P., Burkhardt, P., Christiansen, C., Cooper, C. C., Delmas, P. D., Johnell, O., Johnston, C. C., Kanis, J. A., Lips, P. T. A. M., Melton, L. J., et al. (1994) · Cited by 2,655 · see citing works
(1994) · PubMed · Cited by 2,533 · see citing works
Osteoprotegerin-deficient mice develop early onset osteoporosis and arterial calcification.
Bucay, N., Sarosi, I., Dunstan, C. R., Morony, S., Tarpley, J., Capparelli, C., Scully, S., Tan, H. L., Xu, W., Lacey, D. L., et al. (1998) · Genes & Development · doi:10.1101/gad.12.9.1260 · Cited by 2,483 · see citing works
Lam, J., Takeshita, S., Barker, J. E., Kanagawa, O., Ross, F. P., & Teitelbaum, S. L. (2000) · Journal of Clinical Investigation · doi:10.1172/jci11176 · Cited by 1,440 · cited 1× · see citing works
“TNF-a has been described as a proresorptive cytokine that induces the genesis of osteoclasts by increasing the concentrations of ligandreceptor activator of nuclear factor-jB (RANKL), an osteoclast-activating factor [30].”
BackgroundHofbauer, L. C., Khosla, S., Dunstan, C. R., Lacey, D. L., Boyle, W. J., & Riggs, B. L. (2000) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.2000.15.1.2 · Cited by 1,167 · see citing works
Hofbauer, L. C., Gori, F., Riggs, B. L., Lacey, D. L., Dunstan, C. R., Spelsberg, T. C., & Khosla, S. (1999) · Endocrinology · doi:10.1210/endo.140.10.7034 · Cited by 794 · see citing works
Severe osteoporosis in mice lacking osteoclastogenesis inhibitory factor/osteoprotegerin.
Mizuno, A., Amizuka, N., Irie, K., Murakami, A., Fujise, N., Kanno, T., Sato, Y., Nakagawa, N., Yasuda, H., Mochizuki, S.-I., et al. (1998) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1998.8697 · Cited by 775 · see citing works
Cytokine Production and Treatment Response in Major Depressive Disorder
Lanquillon, S. (2000) · Neuropsychopharmacology · doi:10.1016/s0893-133x(99)00134-7 · Cited by 735 · see citing works
Major Depression and Activation of The Inflammatory Response System
Maes, M. (1999) · Advances in Experimental Medicine and Biology · doi:10.1007/978-0-585-37970-8_2 · Cited by 617 · see citing works
Depression and immune function
Kiecolt-Glaser, J. K., & Glaser, R. (2002) · Journal of Psychosomatic Research · doi:10.1016/s0022-3999(02)00309-4 · Cited by 571 · see citing works
Comorbidity of Psychiatric Diagnoses in Anorexia Nervosa
Halmi, K. A. (1991) · Archives of General Psychiatry · doi:10.1001/archpsyc.1991.01810320036006 · Cited by 509 · see citing works
The effect of a single dose of osteoprotegerin in postmenopausal women.
Bekker, P. J., Holloway, D., Nakanishi, A., Arrighi, M., Leese, P. T., & Dunstan, C. R. (2001) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.2001.16.2.348 · Cited by 484 · see citing works
Bone Mineral Density in Women with Depression
Michelson, D., Stratakis, C., Hill, L., Reynolds, J., Galliven, E., Chrousos, G., & Gold, P. (1996) · New England Journal of Medicine · doi:10.1056/nejm199610173351602 · Cited by 471 · see citing works
O’Dea, J., & Abraham, S. F. (2000) · International Journal of Eating Disorders · doi:10.1002/(sici)1098-108x(200007)28:1 · Cited by 451 · see citing works
The use of the eating disorder examination with children: A pilot study
Bryant‐Waugh, R., Cooper, P. J., Taylor, C. L., & Lask, B. D. (1996) · International Journal of Eating Disorders · doi:10.1002/(sici)1098-108x(199605)19:4 · Cited by 445 · see citing works
Holsboer, F., Lauer, C. J., Schreiber, W., & Krieg, J.-C. (2008) · Neuroendocrinology · doi:10.1159/000127023 · Cited by 369 · see citing works
Depression, Falls, and Risk of Fracture in Older Women
Whooley, M. A. (1999) · Archives of Internal Medicine · doi:10.1001/archinte.159.5.484 · Cited by 348 · see citing works
Grinspoon, S., Thomas, L., Miller, K., Herzog, D., & Klibanski, A. (2002) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.87.6.8574 · Cited by 334 · see citing works
Comorbidity of personality disorders and unipolar major depression: A review
Corruble, E., Ginestet, D., & Guelfi, J. (1996) · Journal of Affective Disorders · doi:10.1016/0165-0327(95)00091-7 · Cited by 191 · see citing works
Cytokines and depression: fortuitous or causative association?
Dantzer, R., Wollman, E., Vitkovic, L., & Yirmiya, R. (1999) · Molecular Psychiatry · doi:10.1038/sj.mp.4000572 · Cited by 174 · see citing works
The prevalence of personality disorders in 210 women with eating disorders.
Herzog, D. B., Keller, M. B., Lavori, P. W., Kenny, G. M., & Sacks, N. R. (1992) · PubMed · Cited by 172 · see citing works
Depression: a major, unrecognized risk factor for osteoporosis?
Cizza, G., Ravn, P., Chrousos, G. P., & Gold, P. W. (2001) · Trends in Endocrinology and Metabolism · doi:10.1016/s1043-2760(01)00407-6 · Cited by 168 · see citing works
Anorexia nervosa in female adolescents: endocrine and bone mineral density disturbances
Muñoz, M., & Argente, J. (2002) · European Journal of Endocrinology · doi:10.1530/eje.0.1470275 · Cited by 163 · see citing works
Chiodini, I., Carnevale, V., Torlontano, M., Fusilli, S., Guglielmi, G., Pileri, M., Modoni, S., Giorgio, A. D., Liuzzi, A., Minisola, S., et al. (1998) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.83.6.4880 · Cited by 154 · see citing works
The hypothalamic-pituitary-adrenal axis in anorexia nervosa
Licinio, J., Wong, M., & Gold, P. W. (1996) · Psychiatry Research · doi:10.1016/0165-1781(96)02991-5 · Cited by 146 · see citing works
Accelerated Osteoporosis in Psychiatric Patients: Possible Pathophysiological Processes
Halbreich, U. M., & Palter, S. F. (1996) · Schizophrenia Bulletin · doi:10.1093/schbul/22.3.447 · Cited by 119 · see citing works
Teraoka, S. N., Malone, K. E., Doody, D. R., Suter, N. M., Ostrander, E. A., Daling, J. R., & CONCANNON, P. J. (2001) · Cancer · doi:10.1002/1097-0142(20010801)92:3 · Cited by 111 · see citing works
The Hypothalamic-Pituitary-Adrenal System in Depression
Heuser, I. (1998) · Pharmacopsychiatry · doi:10.1055/s-2007-979288 · Cited by 106 · see citing works
Involvement of cytokines in eating disorders: a critical review of the human literature
Corcos, M., Guilbaud, O., Paterniti, S., Moussa, M., Chambry, J., Chaouat, G., Consoli, S. M., & Jeammet, P. (2003) · Psychoneuroendocrinology · doi:10.1016/s0306-4530(02)00021-5 · Cited by 104 · see citing works
Karlsson, M. K., Weigall, S., Duan, Y., & Seeman, E. (2000) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.85.9.6796 · Cited by 88 · see citing works
Personality disorders in bipolar and depressive disorders
Rossi, A., Marinangeli, M. G., Butti, G., Scinto, A., Cicco, L. D., Kalyvoka, A., & Petruzzi, C. (2001) · Journal of Affective Disorders · doi:10.1016/s0165-0327(00)00230-5 · Cited by 87 · see citing works
Heer, M. A., Mika, C., Grzella, I., Drummer, C., & Herpertz‐Dahlmann, B. (2002) · Clinical Chemistry · doi:10.1093/clinchem/48.5.754 · Cited by 85 · see citing works
Osteoporosis and pathologic fractures in anorexia nervosa
Brotman, A. W., & Stern, T. A. (1985) · American Journal of Psychiatry · doi:10.1176/ajp.142.4.495 · Cited by 77 · see citing works
Nakai, Y., Hamagaki, S., Takagi, R., Taniguchi, A., & Kurimoto, F. (1999) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.84.4.5589 · Cited by 75 · see citing works
West, D. V., & Maes, M. H. J. (1999) · PubMed · Cited by 70 · see citing works
Increased Bone Remodeling in First-Episode Major Depressive Disorder
Herrán, A., Amado, J., García‐Unzueta, M. T., Vázquez‐Barquero, J. L., Perera, L., & González-Macı́as, J. (2000) · Psychosomatic Medicine · doi:10.1097/00006842-200011000-00006 · Cited by 59 · see citing works
Cytokine mRNA expression patterns in the disease course of female adolescents with anorexia nervosa.
Kahl, K., Kruse, N., Rieckmann, P., & Schmidt, M. (2004) · Psychoneuroendocrinology · doi:10.1016/s0306-4530(02)00131-2 · Cited by 57 · see citing works
Self-citationMechanisms and treatment options for bone loss in anorexia nervosa.
Grinspoon, S. K., Herzog, D. B., & Klibanski, A. (1997) · PubMed · Cited by 43 · see citing works
The hypothalamic-pituitary-adrenal axis in depression.
Meltzer, H. Y., Lowy, M. T., & Koenig, J. I. (1987) · PubMed · Cited by 35 · see citing works
Are Eating Disorders and Affective Disorders Related?
Brotman, A. W., Herzog, D. B., & Weilburg, J. B. (1985) · American Journal of Psychiatry · doi:10.1176/ajp.142.3.391 · Cited by 20 · see citing works
Osteoporosis With Pathologic Hip Fractures in Major Depression
Vort, W. B. V., Rubenstein, M., & Rose, R. P. (1990) · Journal of Geriatric Psychiatry and Neurology · doi:10.1177/089198879000300103 · Cited by 11 · see citing works
Striegel-Moore (1998) · doi:10.1002/(sici)1098-108x(200001)27:1
Flagged first, then by citations
Cited by
Sorted by citations
A Meta-Analysis of Cytokines in Major Depression
Dowlati, Y., Herrmann, N., Swardfager, W., Liu, H., Sham, L., Reim, E. K., & Lanctôt, K. L. (2010) · Biological Psychiatry · doi:10.1016/j.biopsych.2009.09.033 · Cited by 4,729 · see citing works
DE HERT, M., CORRELL, C. U., BOBES, J., CETKOVICH‐BAKMAS, M., COHEN, D., ASAI, I., DETRAUX, J., GAUTAM, S., MÖLLER, H., NDETEI, D. M., et al. (2011) · World Psychiatry · doi:10.1002/j.2051-5545.2011.tb00014.x · Cited by 2,488 · see citing works
Hope, S., Dieset, I., Agartz, I., Steen, N. E., Ueland, T., Melle, I., Aukrust, P., & Andreassen, O. A. (2011) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2011.08.003 · Cited by 164 · see citing works
- Authors
- Kahl, K. G., Rudolf, S., Dibbelt, L., Stoeckelhuber, B. M., Gehl, H.-B., Hohagen, F., & Schweiger, U.
- Affiliations
- University of Lübeck (DE)
- Corresponding author
- Kahl, Kai G.
- Venue
- Osteoporosis International
- Published
- 2004-08-05
- Volume
- 16
- Issue
- 4
- Pages
- 424-429
- ISSN
- 0937-941X (ISSN-L)
- 1433-2965
- OpenAlex
- W2125877367
- Cited by
- 27
- References
- 43
- Citations by year
- 2026: 1 · 2024: 1 · 2022: 2 · 2015: 2 · 2013: 1 · 2012: 2
- FWCI
- 1.62
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Osteoporosis International (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Social Sciences › Psychology › Clinical Psychology › Eating Disorders and Behaviors
- Keywords
- osteoprotegerin, bone turnover markers, major depressive disorder, anorexia nervosa, osteopenia, TNF-α, osteocalcin, C-terminal telopeptide of type I collagen, cytokines, young women
- MeSH terms
- Adolescent, Adult, Anorexia Nervosa, Bone Diseases, Metabolic, Major Depressive Disorder, Female, Glycoproteins, Hormones, Humans, Lumbar Vertebrae, Tumor Necrosis Factor-alpha, Bone Density, Cytokines, Receptors, Tumor Necrosis Factor, Receptors, Cytoplasmic and Nuclear, Osteoprotegerin
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
