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High bone turnover but normal bone mineral density in women suffering from schizophrenia

Published online by Cambridge University Press:  26 March 2008

N. Bergemann*
Affiliation:
Department of General Psychiatry, University of Heidelberg, Heidelberg, Germany
P. Parzer
Affiliation:
Department of Child and Adolescent Psychiatry, University of Heidelberg, Heidelberg, Germany
C. Mundt
Affiliation:
Department of General Psychiatry, University of Heidelberg, Heidelberg, Germany
B. Auler
Affiliation:
Department of General Internal and Psychosomatic Medicine, University of Heidelberg, Heidelberg, Germany
*
*Address for correspondence: N. Bergemann, M.D., M.Sc., Ph.D., Department of General Psychiatry, University of Heidelberg, Voss-Strasse 4, D-69115 Heidelberg, Germany. (Email: niels.bergemann@med.uni-heidelberg.de)

Abstract

Background

A potential association between schizophrenia and osteoporosis or osteopenia has recently been reported. Various factors affect bone mineral density (BMD) such as polydipsia, nicotine, alcohol abuse, lack of physical activity, an unbalanced diet, a lack of ultraviolet exposure and/or vitamin D. In addition, decreased BMD in women with schizophrenia has been attributed to drug-induced hyperprolactinaemia and/or secondary hypogonadism. This study was undertaken because empirical evidence from larger patient cohorts is limited and the data are still controversial.

Method

Seventy-two premenopausal, regularly menstruating women suffering from schizophrenia and 71 age- and sex-matched healthy controls were included in the study. Biochemical markers of bone turnover (serum osteocalcin, urinary pyridinium crosslinks), parathyroid hormone and 25-hydroxyvitamin D were measured. BMD at the femoral neck and lumbar spine was determined by dual-energy X-ray absorptiometry in a subgroup of 59 patients. In addition, 17β-oestradiol, prolactin, testosterone, gonadotrophins and dehydroepiandrosterone sulfate were measured.

Results

Compared with healthy controls, both markers of formation and resorption were increased in women with schizophrenia. However, in the subgroup of 59 patients, BMD was within the normal range. In women suffering from schizophrenia, testosterone levels were higher than in controls, and serum oestradiol levels were lower compared with the normal range.

Conclusion

Despite significantly increased bone turnover, we conclude that premenopausal and regularly menstruating women suffering from schizophrenia have normal spine and hip BMD. This may be due to the opposite effects of the various parameters influencing bone metabolism, especially of the gonadal hormones, and due to an intact coupling mechanism.

Type
Original Articles
Copyright
Copyright © 2008 Cambridge University Press

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References

Abraham, G, Friedman, RH, Verghese, C (1996). Osteoporosis demonstrated by dual energy X-ray absorptiometry in chronic schizophrenic patients. Biological Psychiatry 40, 430431.CrossRefGoogle ScholarPubMed
Abraham, G, Friedman, RH, Verghese, C, de Leon, J (1995). Osteoporosis and schizophrenia: can we limit known risk factors? Biological Psychiatry 38, 131132.CrossRefGoogle ScholarPubMed
Abraham, G, Halbreich, U, Friedman, RH, Josiassen, RC (2002). Bone mineral density and prolactin associations in patients with chronic schizophrenia. Schizophrenia Research 59, 1718.CrossRefGoogle Scholar
Abraham, G, Paing, WW, Kaminski, J, Joseph, A, Kohegy, E, Josiassen, RC (2003). Effects of elevated serum prolactin on bone mineral density and bone metabolism in female patients with schizophrenia: a prospective study. American Journal of Psychiatry 160, 16181620.CrossRefGoogle Scholar
Al-Adwani, A (1997). Neuroleptics and bone mineral density. American Journal of Psychiatry 154, 1173.Google ScholarPubMed
APA (1994). Diagnostic and Statistical Manual of Mental Disorders (DSM-IV), 4th edn. American Psychiatric Press: Washington, DC.Google Scholar
Baastrup, PC, Christiansen, C, Transbol, I (1980). Calcium metabolism in schizophrenic patients on long-term neuroleptic therapy. Neuropsychobiology 6, 5659.CrossRefGoogle ScholarPubMed
Basci, K, Kosa, JP, Borgulya, G, Balla, B, Lazary, A, Nagy, Z, Horvath, C, Speer, G, Lakatos, P (2007). CYP3A7*1C polymorphism, serum dehydroepiandrosterone sulfate level, and bone mineral density in postmenopausal women. Calcified Tissue International 80, 154159.Google Scholar
Becker, D, Liver, O, Mester, R, Rapoport, M, Weizman, A, Weiss, M (2003). Risperidone, but not olanzapine, decreases bone mineral density in female premenopausal schizophrenia patients. Journal of Clinical Psychiatry 64, 761766.CrossRefGoogle Scholar
Bergemann, N, Mundt, C, Parzer, P, Nagl, I, Eckstein-Mannsperger, U, Haisch, S, Salbach, B, Runnebaum, B, Resch, F (2005). Plasma concentration of estradiol in women suffering from schizophrenia treated with conventional and atypical antipsychotics. Schizophrenia Research 73, 357366.CrossRefGoogle ScholarPubMed
Bergemann, N, Parzer, P, Runnebaum, B, Resch, F, Mundt, C (2007). Estrogen, menstrual cycle phases, and psychopathology in women suffering from schizophrenia. Psychological Medicine 37, 14271436.CrossRefGoogle ScholarPubMed
Bilici, M, Cakirbay, H, Guler, M, Tosun, M, Ulgen, M, Tan, U (2002). Classical and atypical neuroleptics, and bone mineral density, in patients with schizophrenia. International Journal of Neuroscience 112, 817828.CrossRefGoogle ScholarPubMed
Delva, NJ, Crammer, JL, Jarzylo, SV, Lawson, JS, Owen, JA, Sribney, M, Weir, BJ, Yendt, ER (1989). Osteopenia, pathological fractures, and increased urinary calcium excretion in schizophrenic patients with polydipsia. Biological Psychiatry 26, 781793.CrossRefGoogle ScholarPubMed
Erler, K (1998). Elecsys immunoassay systems using electrochemiluminescence detection. Wiener Klinische Wochenschrift 110 (Suppl. 3), 59.Google ScholarPubMed
Farhat, G, Yamout, B, Mikati, MA, Demirjian, S, Sawaya, R, El-Hajj Fuleihan, G (2002). Effect of antiepileptic drugs on bone density in ambulatory patients. Neurology 58, 13481353.CrossRefGoogle Scholar
Feldkamp, J, Becker, A, Witte, OW, Scharff, D, Scherbaum, WA (2000). Long-term anticonvulsant therapy leads to low bone mineral density: evidence for direct drug effects of phenytoin and carbamazepine on human osteoblast-like cells. Experimental and Clinical Endocrinology and Diabetes 108, 3743.Google ScholarPubMed
Fujimaki, T, Kurabyashi, T, Ootani, T, Yamamoto, Y, Yasuda, M, Tanaka, K (1994). A study on bone metabolism in women with hyperprolactinemia. Nippon Sanka Fujinka Gakkai Zasshi 46, 423428.Google Scholar
Goff, DC, Henderson, DC, Amico, E (1992). Cigarette smoking in schizophrenia: relationship to psychopathology and medication side effects. American Journal of Psychiatry 149, 11891194.Google ScholarPubMed
Green, AI, Brown, WA (1988). Prolactin and neuroleptic drugs. Endocrinology and Metabolism Clinics of North America 17, 213223.CrossRefGoogle ScholarPubMed
Haddad, PM, Wieck, A (2004). Antipsychotic-induced hyperprolactinemia: mechanisms, clinical features and management. Drugs 64, 22912314.CrossRefGoogle ScholarPubMed
Halbreich, U, Palter, S (1996). Accelerated osteoporosis in psychiatric patients: possible pathophysiological processes. Schizophrenia Bulletin 22, 447454.CrossRefGoogle ScholarPubMed
Halbreich, U, Rojansky, N, Palter, S, Hreshchyshyn, M, Kreeger, J, Bakhai, Y, Rosan, R (1995). Decreased bone mineral density in medicated psychiatric patients. Psychosomatic Medicine 57, 485491.CrossRefGoogle ScholarPubMed
Higuchi, T, Komoda, T, Sugishita, M, Yamazaki, J, Miura, M, Sakagishi, Y, Yamauchi, T (1987). Certain neuroleptics reduce bone mineralization in schizophrenic patients. Neuropsychobiology 18, 185188.CrossRefGoogle ScholarPubMed
Howes, OD, Wheeler, MJ, Meaney, AM, O'Keane, V, Fogelman, I, Blake, G, Murray, RM, Smith, S (2005). Bone mineral density and its relationship to prolactin levels in patients taking antipsychotic treatment. Journal of Clinical Psychopharmacology 25, 259261.CrossRefGoogle ScholarPubMed
Hummer, M, Huber, J (2004). Hyperprolactinaemia and antipsychotic therapy in schizophrenia. Current Medical Research and Opinion 20, 189197.CrossRefGoogle ScholarPubMed
Huston, BK, Bloom, LJ (1975). Constitutional factors, stature, and chronic schizophrenia. Journal of Clinical Psychology 31, 2629.3.0.CO;2-W>CrossRefGoogle Scholar
Kasperk, C, Fitzsimmons, R, Strong, D, Mohann, S, Jennings, J, Wergedal, J, Baylink, D (1990). Studies of the mechanism by which androgens enhance mitogenesis and differentiation in bone cells. Journal of Clinical Endocrinology and Metabolism 71, 13221329.CrossRefGoogle ScholarPubMed
Keely, EJ, Reiss, JP, Drinkwater, DT, Faiman, C (1997). Bone mineral density, sex hormones, and long-term use of neuroleptic agents in men. Endocrine Practice 3, 209213.CrossRefGoogle ScholarPubMed
Lindholm, J, Steiniche, T, Rasmussen, E, Thamsborg, G, Nielsen, IO, Brockstedt-Rasmussen, H (1991). Bone disorder in men with chronic alcoholism: a reversible disease? Journal of Clinical Endocrinology and Metabolism 73, 118124.CrossRefGoogle ScholarPubMed
Mak, TW, Shek, CC, Chow, CC, Wing, YK, Lee, S (1998). Effects of lithium therapy on bone mineral metabolism: a two-year prospective longitudinal study. Journal of Clinical Endocrinology and Metabolism 83, 38573859.Google Scholar
Maric, N, Popovic, V, Jasovic-Gasic, M, Pilipovic, N, van Os, J (2005). Cumulative exposure to estrogen and psychosis: a peak bone mass, case-control study in first-episode psychosis. Schizophrenia Research 73, 351355.CrossRefGoogle ScholarPubMed
McEvoy, JP, Meyer, JM, Goff, DC, Nasrallah, HA, Davis, SM, Sullivan, L, Meltzer, HY, Hsiao, J, Stroup, TS, Lieberman, JA (2005). Prevalence of the metabolic syndrome in patients with schizophrenia: baseline results from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) schizophrenia trial and comparison with national estimates from NHANES III. Schizophrenia Research 80, 1932.CrossRefGoogle ScholarPubMed
Meaney, AM, O'Keane, V (2003). Reduced bone mineral density in patients with schizophrenia receiving prolactin raising anti-psychotic medication. Journal of Psychopharmacology 17, 455458.CrossRefGoogle ScholarPubMed
Meaney, AM, O'Keane, V (2007). Bone mineral density changes over a year in young females with schizophrenia: relationship to medication and endocrine variables. Schizophrenia Research 93, 136143.CrossRefGoogle Scholar
Meaney, AM, Smith, S, Howes, OD, O'Brien, M, Murray, RM, O'Keane, V (2004). Effects of long-term prolactin-raising antipsychotic medication on bone mineral density in patients with schizophrenia. British Journal of Psychiatry 184, 503508.CrossRefGoogle Scholar
Misra, M, Papakostas, GI, Klibanski, A (2004). Effects of psychiatric disorders and psychotropic medications on prolactin and bone metabolism. Journal of Clinical Psychiatry 65, 16071618.CrossRefGoogle ScholarPubMed
Moniz, C (1994). Alcohol and bone. British Medical Bulletin 50, 6775.CrossRefGoogle ScholarPubMed
Naidoo, U, Goff, DC, Klibanski, A (2003). Hyperprolactinemia and bone mineral density: the potential impact of antipsychotic agents. Psychoneuroendocrinology 28, 97108.CrossRefGoogle ScholarPubMed
O'Keane, V, Meaney, AM (2005). Antipsychotic drugs: a new risk factor for osteoporosis in young women with schizophrenia? Journal of Clinical Psychopharmacology 25, 2631.CrossRefGoogle ScholarPubMed
Petty, RG (1999). Prolactin and antipsychotic medications: mechanism of action. Schizophrenia Research 35 (Suppl. 1), 6773.CrossRefGoogle ScholarPubMed
Plenge, P, Rafaelsen, O (1982). Lithium effects on calcium, magnesium and phosphate in man: effects on balance, bone mineral content, faecal and urinary excretion. Acta Psychiatrica Scandinavica 66, 361373.CrossRefGoogle ScholarPubMed
Poole, KE, Reeve, J (2005). Parathyroid hormone – a bone anabolic and catabolic agent. Current Opinion in Pharmacology 5, 612617.CrossRefGoogle ScholarPubMed
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. Analytical Biochemistry 207, 168175.CrossRefGoogle ScholarPubMed
Rogers, GA, Burke, GV (1987). Neuroleptics, prolactin, and osteoporosis. American Journal of Psychiatry 144, 388389.Google ScholarPubMed
Seibel, MJ (2003). Biochemical markers of bone metabolism in the assessment of osteoporosis: useful or not? Journal of Endocrinological Investigation 26, 464471.CrossRefGoogle ScholarPubMed
Seibel, MJ, Baylink, DJ, Farley, JR, Epstein, S, Yamauchi, M, Eastell, R, Pols, HAP, Raisz, LG, Gundberg, CM (1997). Basic science and clinical utility of biochemical markers of bone turnover – a congress report. Experimental and Clinical Endocrinology and Diabetes 105, 125133.CrossRefGoogle ScholarPubMed
Seibel, MJ, Woitge, HW (1999). Basic principles and clinical applications of biochemical markers of bone metabolism. Biochemical and technical aspects. Journal of Clinical Densitometry 2, 299321.CrossRefGoogle ScholarPubMed
Sheth, RD, Wesolowski, CA, Jacob, JC, Penney, S, Hobbs, JE, Bodensteiner, JB (1995). Effect of carbamazepine and valproate on bone mineral density. Journal of Pediatrics 127, 256262.CrossRefGoogle ScholarPubMed
Slemenda, CW (1994). Cigarettes and the skeleton. New England Journal of Medicine 330, 430431.CrossRefGoogle ScholarPubMed
WHO (1993). The ICD-10 Classification of Mental and Behavioural Disorders. Diagnostic Criteria for Research. World Health Organization: Geneva.Google Scholar