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Osteoporosis, Schizophrenia and Antipsychotics

The Need for a Comprehensive Multifactorial Evaluation

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Abstract

Osteoporosis is recognised as a major public health issue leading to bone fractures, pain and disability. Awareness of an elevated risk of osteoporosis in individuals with schizophrenia is increasing.

An accelerated decrease in bone mineral density (BMD) in patients with schizophrenia may be disease related or drug induced. A drug-induced decrease in BMD has been attributed mostly to hyperprolactinaemia and its consequences. However, as demonstrated in this review, decreased BMD and osteoporosis are multifactorial processes, and abnormal bone structure and functions are not limited to BMD. Multiple dynamic processes may lead to impairment of bone homeostasis and eventually to bone abnormalities. Many of these processes may be abnormal in treated as well as untreated patients with schizophrenia.

Despite many publications, the epidemiology of abnormal bone structure, mineralisation and dynamics in patients with schizophrenia is still not fully determined. Comprehensive studies of bone dynamics in individuals with first-episode schizophrenia, as well as in patients treated with various current medications, are needed in order to characterise the problem(s) and then to develop relevant treatment and prevention strategies.

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References

  1. Osteoporosis prevention, diagnosis, and therapy. NIH Consens Statement 2000; 17: 1–45

    Google Scholar 

  2. NIH Consensus Conference Development Panel on Osteoporosis Prevention Diagnosis and Therapy. Osteoporosis prevention, diagnosis, and therapy. JAMA 2001; 285(6): 785–95

    Article  Google Scholar 

  3. World Health Organization Study Group. Assessment of fracture risk and its application to screening for postmenopausal osteoporosis. Geneva: World Health Organization, 1994. WHO technical report series no. 843

    Google Scholar 

  4. Kanis JA. Assessment of fracture risk and its application to screening for postmenopausal osteoporosis: synopsis of a WHO report. WHO Study Group. Osteoporos Int 1994; 4: 368–81

    Article  PubMed  CAS  Google Scholar 

  5. Gourlay ML, Brown SA. Clinical considerations in premenopausal osteoporosis. Arch Intern Med 2004; 164: 603–14

    Article  PubMed  Google Scholar 

  6. Khan A, Syed Z. Bone densitometry in premenopausal women. J Clin Densitometry 2004; 7: 90–7

    Google Scholar 

  7. Bonnick S. Nichols D, Sanborn C, et al. Dissimilar spine and femoral Z-score in premenopausal women. Calcif Tissue Int 1997; 61: 263–5

    Article  PubMed  CAS  Google Scholar 

  8. Ryan P. Bone densitometry in the management of Colles’ fractures: which site to measure? Br J Radiol 2001; 74: 1137–41

    PubMed  CAS  Google Scholar 

  9. Marshall D, Johnell O, Wedel H. Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures. BMJ 1996; 312: 1254–9

    Article  PubMed  CAS  Google Scholar 

  10. Garnero P, Borel O, Sornay-Rendu E, et al. Vitamin D receptor gene polymorphisms do not predict bone turnover and bone mass in healthy premenopausal women. J Bone Miner Res 1995; 10: 1283–8

    Article  PubMed  CAS  Google Scholar 

  11. Garnero P, Sornay-Rendu E, Claustrat B, et al. Biochemical markers of bone turnover, endogenous hormones and the risk of fractures in postmenopausal women: the OFLY study. J Bone Miner Res 2000; 15: 1526–36

    Article  PubMed  CAS  Google Scholar 

  12. Halbreich U, Palter S. Accelerated osteoporosis in psychiatric patients: possible pathophysiological processes. Schizophr Bull 1996; 22(3): 447–54

    Article  PubMed  CAS  Google Scholar 

  13. Riggs BL. Osteoporosis: a disease of impaired homeostatic regulation [editorial]. Miner Electrolyte Metab 1981; 5: 265–72

    CAS  Google Scholar 

  14. Steele FR. Evolutions: bone remodeling. J NIH Res 1995; 7: 78–87

    Google Scholar 

  15. Hattner R, Epker BN, Frost HM. Suggested sequential mode of control of changes in cell behavior in adult bone remodeling. Nature 1965; 206: 489–90

    Article  PubMed  CAS  Google Scholar 

  16. Halbreich U, Kahn LS. Hormonal aspects of schizophrenias: an overview. Psychoneuroendocrinol 2003; 28Suppl. 2: 1–16

    CAS  Google Scholar 

  17. Hafner H. Gender differences in schizophrenia. Psychoneuroen-docrinology 2003; 28Suppl. 2: 17–54

    Article  Google Scholar 

  18. Hahn TJ. Drug induced disorders of vitamin D, and mineral metabolism. J Clin Endocrinol Metab 1980; 9: 107

    Article  CAS  Google Scholar 

  19. Lindsay R, Aitkin JM, Anderson JB, et al. Long-term prevention of post menopausal osteoporosis by oestrogen. Lancet 1976; 1: 1038–41

    Article  PubMed  CAS  Google Scholar 

  20. Seeman E, Melton III LJ, O’Fallon WM, et al. Risk factors for spinal osteoporosis in men. Am J Med 1983; 75: 977–83

    Article  PubMed  CAS  Google Scholar 

  21. Cummings S, Bates D, Black D. Clinical use of bone densitometry: scientific review. JAMA 2002; 288: 1889–900

    Article  PubMed  Google Scholar 

  22. Forresta C, Zannatta GP, Busnardo B, et al. Testosterone and calcitonin plasma levels in hypogonadal osteoporotic young men. J Endocrino Invest 1985; 8: 377–9

    Google Scholar 

  23. Forresta C, Scanelli G, Sanatta GP, et al. Reduced calcitonin reserve in young hypogonadic osteoporosis men. Horm Metab Res 1987; 19(6): 275–7

    Article  Google Scholar 

  24. Francis RM, Peacock M, Aaron HJE, et al. Osteoporosis in hypogonadal men: role of decreased plasma, 1,25-dihydrox-yvitamin D, calcium malabsorption, and low bone formation. Bone 1986; 7: 261–8

    Article  PubMed  CAS  Google Scholar 

  25. Rigotti NA, Neer RM, Jameson L. Osteopenia and bone fractures in a man with anorexia nervosa and hypogonadism. JAMA 1986; 256: 385–8

    Article  PubMed  CAS  Google Scholar 

  26. Stanley HL, Schmitt BP, Poses RM, et al. Does hypogonadism contribute to the occurrence of minimal trauma hip fracture in elderly men? J Am Geriatrics Soc 1991; 39: 766–71

    CAS  Google Scholar 

  27. Mundy RT. Cytokines and growth factors in the regulation of bone remodeling. J Bone Miner Res 1993; 8 Suppl. 2: 505–10

    Google Scholar 

  28. Rapaport MH, McAllister CC, Pickar D, et al. Elevated levels of soluble interleukin-1 receptors in schizophrenia. Arch Gen Psychiatry 1989; 46: 291–2

    Article  PubMed  CAS  Google Scholar 

  29. Licinio J, Scibyl JP, Altemus M, et al. Elevated CSF levels of interleukin-2 in neuroleptic-free schizophrenic patients. Am J Psychiatry 1993; 150: 1408–10

    PubMed  CAS  Google Scholar 

  30. Gown M, Nedwin GE, Mundy GR. Preferential inhibition of cytokine-stimulated bone resorption by recombinant interferon gamma. J Bone Miner Res 1986; 1: 469–74

    Article  Google Scholar 

  31. Konig A, Muhlbauer RC, Fleisch H. Tumor necrosis factor α and interleukin-1 stimulate bone resorption in vivo as measured by urinary [3H] tetracycline excretion from prelabled mice. J Bone Miner Res 1988; 3: 621–7

    Article  PubMed  CAS  Google Scholar 

  32. Bertolini DR, Nedwin GE, Bringman TS, et al. Stimulation of bone resorption inhibition of bone formation in vitro by human tumor necrosis factors. Nature 1986; 319: 516–8

    Article  PubMed  CAS  Google Scholar 

  33. Vignery A, Niven-Fairchild T, Chepard M. Recombinant mutine interferon-γ inhibits the fusion of mouse alveolar macrophages in vitro but stimulates the formation of osteoporosis-like cells on implanted syngenic bone particles in vivo. J Bone Miner Res 1990; 5(6): 637–44

    Article  PubMed  CAS  Google Scholar 

  34. Musso T, Espinoza-Delgado I, Pulkki K, et al. IL-2 induces IL-6 production in human monocytes. J Immuno 1992; 148: 795–800

    CAS  Google Scholar 

  35. Lindsay R, Cosman F. Osteoporosis. In: Braunwald E, Fauci AS, Isselbacher KJ, editors. Harrison’s principles of internal medicine. 15th ed. New York: McGraw-Hill, 2001: 2226–37

    Google Scholar 

  36. Mackay-Sim A, Feron F, Elyes D, et al. Schizophrenia, vitamin D and brain development. Int Rev Neurobiol 2004; 59: 351–80

    Article  PubMed  CAS  Google Scholar 

  37. Canuso C, Goldstein J, Wojcik J, et al. Antipsychotic medication, prolactin elevation, and ovarian function in women with schizophrenia and schizoaffective disorder. Psychiatry Res 2002; 111: 11–20

    Article  PubMed  CAS  Google Scholar 

  38. Huber T, Rollnik J, Wilhelms J, et al. Estradiol levels in psychotic disorders. Psychoneuroendocrinology 2001; 26: 27–35

    Article  PubMed  CAS  Google Scholar 

  39. Canter-Graae E, Nordstrom LG, McNeil TF. Substance abuse in schizophrenia: a review of the literature and a study of correlates in Sweden. Schizophr Bull 2001; 48: 69–82

    Google Scholar 

  40. Goff D, Henderson D, Amico E. Cigarette smoking in schizophrenia, relationship to psychopathology and medication side effects. Am J Psychiatry 1992; 149: 1189–94

    PubMed  CAS  Google Scholar 

  41. Delva NJ, Crammer JL, Jarzylo SV, et al. Osteopenia, pathological fractures, and increased calcium excretion in schizophrenic patients with polydipsia. Biol Psychiatry 1989; 26: 781–93

    Article  PubMed  CAS  Google Scholar 

  42. DeLeon J, Verghese C, Tracy JI, et al. Polydipsia and water intoxication in psychiatric patients: a review of the epidemiological literature. Biol Psychiatry 1994; 35: 408–19

    Article  CAS  Google Scholar 

  43. Halbreich U, Rojansky N, Palter S, et al. Decreased bone mineral density in medicated psychiatric patients. Psychosom Med 1995; 57: 485–91

    PubMed  CAS  Google Scholar 

  44. Tandon R, Halbreich U. The second-generation ‘atypical’ antipsychotics: similar improved efficacy but different neuroendocrine side effects. Psychoneuroendocrinology 2003; 28: 1–7

    Article  PubMed  CAS  Google Scholar 

  45. Halbreich U, Kahn L. Hyperprolactinemia and schizophrenia: mechanisms and clinical aspects. J Psychiatr Pract 2003; 9: 344–53

    Article  PubMed  Google Scholar 

  46. Halbreich U, Kinon BA, Gilmore JA, et al. Elevated prolactin levels in patients with schizophrenia: mechanisms and related adverse effects. Psychoneuroendocrinology 2003; 28: 53–68

    Article  PubMed  CAS  Google Scholar 

  47. Christian JC, Yu PL, Slemenda CW, et al. Heritability of bone mass: a longitudinal study in aging male twins. Am J Hum Genet 1989; 44: 429–33

    PubMed  CAS  Google Scholar 

  48. Pocock NA, Eisman JA, Hopper JL, et al. Genetic determinants of bone mass in adults: a twin study. J Clin Invest 1987; 80: 706–10

    Article  PubMed  CAS  Google Scholar 

  49. Gueguen R, Jouanny P, Guillemin F, et al. Segregation analysis and variance components analysis of bone mineral density in healthy families. J Bone Miner Res 1995; 10: 2017–22

    Article  PubMed  CAS  Google Scholar 

  50. Garnero P, Arden NK, Griffiths G, et al. Genetic influence on bone turnover in postmenopausal twins. J Clin Endocrinol Metab 1996; 81: 140–6

    Article  PubMed  CAS  Google Scholar 

  51. Seeman E, Hooper JL, Bach LA, et al. Reduced bone mass in daughters of women with osteoporosis. N Eng J Med 1989; 320: 554–8

    Article  CAS  Google Scholar 

  52. Ralston SH. Genetic control of susceptibility to osteoporosis. J Clin Endocrinol Metab 2002; 87(6): 2460–6

    Article  PubMed  CAS  Google Scholar 

  53. Krall EA, Dawson-Hughes B. Heritable and life-style determinants of bone mineral density. J Bone Miner Res 1993; 8(1): 1–9

    Article  PubMed  CAS  Google Scholar 

  54. Salamone LM, Cauley JA, Black DM, et al. Effect of a lifestyle intervention on bone mineral density in premenopausal women: a randomized trial. Am J Clin Nutr 1999; 70: 97–103

    PubMed  CAS  Google Scholar 

  55. Eccleshall TR, Garnero P, Gross C, et al. Lack of correlation between start codon polymorphism of the vitamin D receptor gene and bone mineral density in premenopausal French women. The OFELY study. J Bone Miner Res 1998; 13: 31–5

    Article  CAS  Google Scholar 

  56. Graafmans WC, Lips P, Ooms ME, et al. The effect of vitamin D supplementation on the bone mineral density of the femoral neck is associated with the vitamin D receptor genotype. J Bone Miner Res 1997; 12: 1241–5

    Article  PubMed  CAS  Google Scholar 

  57. Spotila LD, Caminis J, Johnston R, et al. Vitamin D receptor genotype is not associated with bone mineral density in three ethnic/regional groups. Calcif Tissue Int 1996; 59: 235–7

    Article  PubMed  CAS  Google Scholar 

  58. Jarvinen TL, Jarvinen TA, Sievanen H, et al. Vitamin D receptor alleles and bone’s response to physical activity. Calcif Tissue Int 1998; 62: 413–7

    Article  PubMed  CAS  Google Scholar 

  59. Morrison NA, Yeoman R, Kelly PJ, et al. Contribution of transacting factor alleles to normal physiological variability: vitamin D receptor gene polymorphisms and circulating osteocalcin. Proc Natl Acad Sci U S A 1992; 89: 6665–9

    Article  PubMed  CAS  Google Scholar 

  60. Morrison NA, Qi JC, Tokita A, et al. Prediction of bone density from vitamin D receptor alleles. Nature 1994; 367: 284–7

    Article  PubMed  CAS  Google Scholar 

  61. Gong G, Stern HS, Cheng SC, et al. The association of bone mineral density with vitamin D receptor gene polymorphisms. Osteoporos Int 1999; 9: 55–64

    Article  PubMed  CAS  Google Scholar 

  62. Mizunuma H, Hosoi T, Okano H, et al. Estrogen receptor gene polymorphism and bone mineral density at the lumbar spine of pre- and post- menopausal women. Bone 1997; 21: 379–83

    Article  PubMed  CAS  Google Scholar 

  63. Ho A, Yeung SS, Kung AW. PvuII polymorphism of the estrogen receptor α and bone mineral density in healthy southern Chinese women. Calcif Tissue Int 2000; 66: 405–8

    Article  PubMed  CAS  Google Scholar 

  64. Albagha OME, McGuigan FE, Reid DM, et al. Estrogen receptor alpha gene polymorphisms and bone mineral density: haplotype analysis in women from the United Kingdom. J Bone Miner Res 2001; 16: 128–34

    Article  PubMed  CAS  Google Scholar 

  65. Sano M, Inoue S, Hosoi T, et al. Association of estrogen receptor dinucleotide repeat polymorphism with osteoporosis. Biochem Biophys Res Commun 1995; 217: 378–83

    Article  PubMed  CAS  Google Scholar 

  66. Sowers M, Willing M, Burns T, et al. Genetic markers, bone mineral density and serum osteocalcin levels. J Bone Miner Res 1999; 14: 1411–9

    Article  PubMed  CAS  Google Scholar 

  67. Kobayashi S, Inoue S, Hosoi T, et al. Association of bone mineral density with polymorphisms of the estrogen receptor gene in post-menopausal women. J Bone Miner Res 1996; 11: 306–11

    Article  PubMed  CAS  Google Scholar 

  68. Willing M, Sowers M, Aron D, et al. Bone mineral density and its change in white women: estrogen and vitamin D receptor genotypes and their interaction. J Bone Miner Res 1998; 13: 695–705

    Article  PubMed  CAS  Google Scholar 

  69. Salmen T, Heikkinen AM, Mahonen A, et al. Early postmenopausal bone loss is associated with PvuII estrogen receptor gene polymorphism in Finnish women: effect of hormone replacement therapy. J Bone Miner Res 2000; 15: 315–21

    Article  PubMed  CAS  Google Scholar 

  70. Weel AE, van der Klift M, Hofman A, et al. The effect of estrogen receptor alpha polymorphism on bone mineral density and fractures in men and women [abstract]. Calcif Tissue Int 2001; 67: 487

    Google Scholar 

  71. Sriussadaporn S, Srimuninnimit V, Ploybutr S, et al. Association between estrogen receptor concentration in breast cancer tissue and bone mineral density. J Med Assoc Thai 2002; 85: 327–33

    PubMed  Google Scholar 

  72. Hampson G, Evans C, Petitt RJ, et al. Bone mineral density, collagen type 1 alpha genotypes and bone turnover in premenopausal women with diabetes mellitus. Diabetologia 1998; 41: 1314–20

    Article  PubMed  CAS  Google Scholar 

  73. Rosen C, Kurland E, Verault D, et al. Association between serum insulin growth factor-I (IGF-I) and a simple sequence repeat in IGF-I gene: implications for genetic studies of bone mineral density. J Clin Endocrinol Metab 1998; 83: 2286–90

    Article  PubMed  CAS  Google Scholar 

  74. Takacs J, Koller D, Peacock M, et al. Sibling pair linkage and association between bone mineral density and insulin-like growth factor I gene locus. J Clin Endocrinol Metab 1999; 84: 4467–71

    Article  PubMed  CAS  Google Scholar 

  75. Langdahl BL, Lokke E, Carstens M, et al. Osteoporotic fractures are associated with an 86-base pair repeat polymorphism in the interleukin-1-receptor antagonist gene but not with polymorphism in the interleukin-1 beta gene. J Bone Miner Res 2000; 15: 402–14

    Article  PubMed  CAS  Google Scholar 

  76. Murray RE, McGuigan F, Grant SFA, et al. Polymorphisms of the interleukin-6 gene are associated with bone mineral density. Bone 1997; 21: 89–92

    Article  PubMed  CAS  Google Scholar 

  77. Spotila LD, Rodrigue H, Koch M, et al. Association of polymorphism in the TNFR2 gene with low bone mineral density. J Bone Miner Res 2000; 15: 1376–83

    Article  PubMed  CAS  Google Scholar 

  78. Wallace B, Cumming R. Systematic review of randomized trials of the effect of exercise on bone mass in pre-and post-menopausal women. Calcif Tissue Int 2000; 67: 10–8

    Article  PubMed  CAS  Google Scholar 

  79. Heaney RP. Role and importance of calcium in preventing and managing osteoporosis. Medscape 2006; 5237: 1–18

    Google Scholar 

  80. Chapuy MC, Arlot ME, Duboeuf F, et al. Vitamin D3 and calcium to prevent hip fractures in the elderly women. N Engl J Med 1992; 327: 1637–42

    Article  PubMed  CAS  Google Scholar 

  81. Ward KD, Klesges RC. A meta-analysis of the effects of cigarette smoking on bone mineral density. Calcif Tissue Int 2001; 68: 259–70

    Article  PubMed  CAS  Google Scholar 

  82. Law MR, Hackshaw AK. A meta-analysis of cigarette smoking, bone mineral density and risk of hip fracture: recognition of a major effect. BMJ 1997; 315: 841–6

    Article  PubMed  CAS  Google Scholar 

  83. Halbreich U. The association between pregnancy processes, low birth weight, preterm delivery and post partum depression: the need for interdisciplinary integration. Am J Obstet Gynecol 2005; 193(4): 1312–22

    Article  PubMed  Google Scholar 

  84. Barker DJP. Fetal and infant origin of adult disease. London: BMJ Publishing Group, 1992

    Google Scholar 

  85. Hafner H, Maurer K, Loffler W, et al. The epidemiology of early schizophrenia: influence of age and gender on onset and early course. Br J Psychiatry 1994; 23: 29–38

    Google Scholar 

  86. Lewine RR. Sex differences in age of symptom onset and first hospitalization in schizophrenia. Am J Orthopsychiatry 1980; 50(2): 316–22

    Article  PubMed  CAS  Google Scholar 

  87. Seeman MV. Gender differences in schizophrenia. Can J Psychiatry 1982; 27: 107–12

    PubMed  CAS  Google Scholar 

  88. Angermeyer MC, Kühn L. Gender differences in age at onset of schizophrenia. Eur Arch Psychiatry Neurol Sci 1988; 237: 351–64

    Article  PubMed  CAS  Google Scholar 

  89. Jablensky A, Sartorius N, Ernberg G, et al. Schizophrenia: manifestations, incidence and course in different cultures. A World Health Organization ten-country study [published erratum appears in Psychol Med Monogr Suppl 1992; 22 (4): following 1092]. Psychol Med Monogr Suppl 1992; 20: 1–97

    CAS  Google Scholar 

  90. Hambrecht M, Maurer K, Sartorius N, et al. Transnational stability of gender differences in schizophrenia? An analysis based on the WHO study on determinants of outcome of severe mental disorders. Eur Arch Psychiatry Clin Neurosci 1992; 242: 6–12

    Article  PubMed  CAS  Google Scholar 

  91. Bonjour J, Theintz G, Buchs B, et al. Critical years and stages of puberty for spinal and femoral bone mass accumulation during adolescence. J Clin Endocrinol Metab 1991; 73: 555–63

    Article  PubMed  CAS  Google Scholar 

  92. Lofman O, Larsson L, Toss G. Bone mineral density in diagnosis of osteoporosis: reference population, definition of peak bone mass, and measured site determine prevalence. J Clin Densitom 2000; 3: 177–86

    Article  PubMed  CAS  Google Scholar 

  93. Tenenhouse A, Joseph L, Kreiger N, et al. Estimation of the prevalence of low bone density in Canadian women and men using a population-specific DXA reference standard: the Canadian Multicentre Osteoporosis Study (CaMos). Osteoporos Int 2000; 11: 897–904

    Article  PubMed  CAS  Google Scholar 

  94. Heaney R, Abrams S, Dawson-Hughes B, et al. Peak bone mass. Osteoporos Int 2000; 11: 985–1009

    Article  PubMed  CAS  Google Scholar 

  95. Soyka L, Fairfield W, Klibanski A. Hormonal determinants and disorders of peak bone mass in children. J Clin Endocrinol Metab 2000; 85: 3951–63

    Article  PubMed  CAS  Google Scholar 

  96. Kavanagh DJ, McGrath J, Saunders JB, et al. Substance misuse in patients with schizophrenia: epidemiology and management. Drugs 2002; 62: 743–55

    Article  PubMed  Google Scholar 

  97. Halbreich U, Asnis GM, Schildledeckar R, et al. Cortisol secretion in endogenous depression: I. Basal plasma levels. Arch Gen Psychiatr 1985; 42: 904–8

    CAS  Google Scholar 

  98. Schweiger U, Deusche M, Korne A, et al. Low lumbar bone mineral density in patients with major depression. Am J Psychiatry 1994; 151: 1691–3

    PubMed  CAS  Google Scholar 

  99. Michelson D, Stratakis C, Hill Z, et al. Bone mineral density in women with depression. N Engl J Med 1996; 335: 1176–81

    Article  PubMed  CAS  Google Scholar 

  100. Thakore JH. Metabolic syndrome and schizophrenia. Br J Psychiatry 2005; 186: 455–65

    Article  PubMed  Google Scholar 

  101. Friedman JH. Atypical antipsychotics in the EPS-vulnerable patient. Psychoneuroendocrinology 2003; 28: 39–51

    Article  PubMed  CAS  Google Scholar 

  102. Kasper S, Resinger E. Cognitive effects and antipsychotic treatment. Psychoneuroendocrinology 2003; 28: 27–38

    Article  PubMed  CAS  Google Scholar 

  103. Haddad PM, Wieck A. Antipsychotic-induced hyperprolactinemia: mechanisms, clinical features and management. Drugs 2004; 64: 2291–314

    Article  PubMed  CAS  Google Scholar 

  104. Cuttler AJ. Sexual dysfunction and antipsychotic treatment. Psychoneuroendocrinology 2003; 28: 69–82

    Article  Google Scholar 

  105. Gruen P, Sachar E, Langer G, et al. Prolactin responses to neuroleptics in normal and schizophrenic subjects. Arch Gen Psychiatry 1978; 35: 108–16

    Article  PubMed  CAS  Google Scholar 

  106. Gruen P, Sachar E, Altman N, et al. Relation of plasma prolactin to clinical response in schizophrenic patients. Arch Gen Psychiatry 1978; 35: 1222–7

    Article  PubMed  CAS  Google Scholar 

  107. Langer G, Sachar EJ, Gruen PH, et al. Human prolactin responses to neuroleptic drugs correlate with antischizophrenic potency. Nature 1997; 266: 639–40

    Article  Google Scholar 

  108. Langer G, Sachar EJ. Dopaminergic factors in human prolactin regulation: effects of neuroleptics and dopamine. Psychoneuroendocrinology 1978; 2: 373–8

    Article  Google Scholar 

  109. Crawford AM, Beasley Jr C, Tollefson G. The acute and long-term effect of olanzapine compared with placebo and haloperidol on serum prolactin concentrations. Schizophr Res 1997; 26: 41–54

    Article  PubMed  CAS  Google Scholar 

  110. Tollefson GD, Beasley Jr CM, Tran PV, et al. Olanzapine versus haloperidol in the treatment of schizophrenia and schizoaffective and schizophreniform disorders: results of an international collaborative trial. Am J Psychiatry 1997; 154(4): 457–65

    PubMed  CAS  Google Scholar 

  111. Beasley CM, Tollefson G, Tran P, et al. Olanzapine versus placebo and haloperidol: acute phase results of the North American double-blind olanzapine trial. Neuropsychopharmacology 1996; 14: 111–23

    Article  PubMed  CAS  Google Scholar 

  112. Arvanitis LA, Miller BG. Multiple fixed doses of ‘Seroquel’ (quetiapine) in patients with acute exacerbation of schizophrenia: a comparison with haloperidol and placebo. Biol Psychiatry 1997; 42(4): 233–46

    Article  PubMed  CAS  Google Scholar 

  113. Goff DC, Evins AE. Negative symptoms in schizophrenia: neurobiological models and treatment response. Harv Rev Psychiatry 1998; 6(2): 59–77

    Article  PubMed  CAS  Google Scholar 

  114. Tran PV, Hamilton SH, Kuntz AJ, et al. Double-blind comparison of olanzapine versus risperidone in the treatment of schizophrenia and other psychotic disorders. J Clin Psychopharmacol 1998; 17: 407–18

    Article  Google Scholar 

  115. Meltzer HY, Goode DJ, Schyee PM, et al. Effect of clozapine on human serum prolactin levels. Am J Psychiatry 1979; 136: 1550–5

    PubMed  CAS  Google Scholar 

  116. Casey DE. Side effect profiles of new antipsychotic agents. J Clin Psychiatry 1996; 57(11): 40–5; discussion 46-52

    PubMed  CAS  Google Scholar 

  117. Lee HS, Kim CH, Song DH, et al. Clozapine does not elevate serum prolactin levels in healthy men. Biol Psychiatry 1997; 38: 762–4

    Article  Google Scholar 

  118. Kane JM, Cooper TB, Sachar EJ, et al. Clozapine: plasma levels and prolactin response. Psychopharmacology 1981; 73(2): 184–7

    Article  PubMed  CAS  Google Scholar 

  119. Breier A, Malhotra AD, Su TP, et al. Clozapine and risperidone in chronic schizophrenia: effects on symptomatology, parkinsonian side effects, and neuroendocrine response. Am J Psychiatry 1999; 156: 294–8

    PubMed  CAS  Google Scholar 

  120. Kinon BJ, Basson BR, Gilmore JA, et al. Strategies for switching from conventional antipsychotic drugs or risperidone to olanzapine. J Clin Psychiatry 2000; 61(11): 833–40

    Article  PubMed  CAS  Google Scholar 

  121. Angrist BM, Baldessarini PJ, Bowers MB, et al. Treatment of schizophrenia. J Clin Psychiatry 1999; 60(11): 3–80

    Google Scholar 

  122. David S, Taylor C, Kinon BJ, et al. The effects of olanzapine, risperidone, and haloperidol on plasma prolactin levels in patients with schizophrenia. Clin Ther 2000; 22(9): 1085–96

    Article  PubMed  CAS  Google Scholar 

  123. Kinon BJ, Gilmore JA, Liu H, et al. Hyperprolactinemia in response to antipsychotic drugs: characterization across comparative clinical trials. Psychoneuroendocrinology 2003; 28 Suppl. 2: 69–82

    Article  CAS  Google Scholar 

  124. Small JG, Hirsch SR, Arvanitis LA, et al. Quetiapine in patients with schizophrenia: a high- and low-dose double-blind comparison with placebo. Arch Gen Psychiatry 1997; 54(6): 549–57

    Article  PubMed  CAS  Google Scholar 

  125. Borrison RL, Arvantis LA, Miller BG. ICI 204,636, an atypical antipsychotic: efficacy and safety in a multicenter, placebocontrolled trial in patients with schizophrenia. US Seroquel Study Group. J Clin Psychopharmacol 1996; 16: 158–69

    Article  Google Scholar 

  126. Goff D, Posever T, Herz L. An explanatory haloperidol-controlled dose-finding study of ziprasidone in hospitalized patients with schizophrenia or schizoaffective disorder. J Clin Psychopharmacology 1998; 18: 296–304

    Article  CAS  Google Scholar 

  127. Tannirandorn P, Epstein S. Drug-induced bone loss. Osteoporosis Int 2000; 11: 637–59

    Article  CAS  Google Scholar 

  128. Abraham G, Paing W, Kaminski J, et al. Effects of elevated serum prolactin on bone mineral density and bone metabolism in female patients with schizophrenia: a prospective study. Am J Psychiatry 1998; 160: 1618–20

    Article  Google Scholar 

  129. Abraham G, Friedman HR, Verghese C, et al. Osteoporosis and schizophrenia: can we limit known risk factors? Biol Psychiatry 1995; 38(2): 131–2

    Article  PubMed  CAS  Google Scholar 

  130. Meaney AM, O’Keane V. Reduced bone mineral density in patients with schizophrenia receiving prolactin raising antipsychotic medication. J Psychopharmacol 2003; 17: 455–8

    Article  PubMed  CAS  Google Scholar 

  131. Meaney AM, Smith OD, Howes M, et al. Effects of long-term prolactin-raising antipsychotic medication on bone mineral density in patients with schizophrenia. Br J Psychiatry 2004; 184: 503–8

    Article  PubMed  CAS  Google Scholar 

  132. O’Keane V, Meaney AM. Antipsychotic drugs: a new risk factor for osteoporosis in young women with schizophrenia? J Clin Psychopharmacol 2005; 25(1): 26–31

    Article  PubMed  CAS  Google Scholar 

  133. Misra M, Papakostas GI, Kilbanski A. Effects of psychiatric disorders and psychotropic medications on prolactin and bone metabolism. J Clin Psychiatry 2004; 65: 1607–18

    Article  PubMed  CAS  Google Scholar 

  134. Ataya K, Mercado A, Kartaginer J, et al. Bone density and reproductive hormones in patients with neuroleptic-induced hyperprolactinemia. Fertil Steril 1988; 50: 876–81

    PubMed  CAS  Google Scholar 

  135. Dickson RA, Glazer WM. Neuroleptic-induced hyperprolactinemia. Schizophr Res 1999; 35 Suppl.: S75–86

    Article  PubMed  Google Scholar 

  136. Bilici M, Cakirbay H, Guler M, et al. Classical and atypical neuroleptics, and bone mineral density in patients with schizophrenia. Int J Neurosci 2002; 112: 817–28

    Article  PubMed  Google Scholar 

  137. Kartaginer J, Ataya K, Mercado A, et al. Osteoporosis associated with neuroleptic treatment: a case report. J Reprod Med 1990; 35: 198–202

    PubMed  CAS  Google Scholar 

  138. Keely E, Reiss JP, Drinkwater DT, et al. Bone mineral density, sex hormones and long term use of neuroleptic agents in men. Endocrin Pract 1997; 3: 209–13

    CAS  Google Scholar 

  139. Becker D, Liver O, Mester R, et al. Risperidone, but not olanzapine decreases bone mineral density in female premenopausal schizophrenia patients. J Clin Psychiatry 2003; 64: 761–6

    Article  PubMed  CAS  Google Scholar 

  140. Lean M, De Smedt G. Schizophrenia and osteoporosis. Int Clin Psychopharmacol 2004; 19: 31–5

    Article  PubMed  Google Scholar 

  141. Malik P. Dissertation for the degree of Doctor in General Medicine. Innsbruck: Medical Faculty of the Leopold-Frazens University, 2001

    Google Scholar 

  142. Hummer M, Malik P, Gasser RW, et al. Osteoporosis in patients with schizophrenia. Am J Psychiatry 2005; 162: 162–7

    Article  PubMed  Google Scholar 

  143. Abraham G, Halbreich U, Friedman RH, et al. Bone mineral density and prolactin associations in patients with chronic schizophrenia. Schizophr Res 2003; 59: 17–8

    Article  PubMed  Google Scholar 

  144. Liu-Scifert H, Kinon BJ, Ahl J, et al. Osteopenia associated with increased prolactin and aging in psychiatric patients treated with prolactin-elevating antipsychotics. Ann N Y Acad Sci 2004; 1032: 297–8

    Article  Google Scholar 

  145. Howes OD, Wheeler MJ, Meaney AM, et al. Bone mineral density and its relationship to prolactin levels in patients taking antipsychotic treatment. J Clin Psychopharmacol 2005; 25(3): 259–61

    Article  PubMed  CAS  Google Scholar 

  146. Klibanski A, Neer R, Beitims I, et al. Decreased bone density in hyperprolactinemic women. N Engl J Med 1981; 303: 1511–4

    Article  Google Scholar 

  147. Schlecte JA, Sherman B, Martin R. Bone density in amenorrheic women with and without hyperprolactinemia. J Clin Endocrinol Metab 1983; 56: 1120–3

    Article  Google Scholar 

  148. Schlecte J, Walkner L, Kathol M. A longitudinal analysis of premenopausal bone loss in healthy women and women with hyperprolactinemia. J Clin Endocrinol Metab 1992; 75: 698–702

    Article  Google Scholar 

  149. Bergemann N, Auler B, Parzer P, et al. High bone turnover but normal bone mineral density in women with schizophrenia [abstract]. Bone 2001; 28: 248

    Google Scholar 

  150. Naido U, Goff DC, Klibansky A. Hyperprolactinemia and bone mineral density: the potential impact of antipsychotic agents. Psychoneuroendocrinology 2003; (28): 97-108

  151. Calvo MS, Eyre DR, Gundberg CM. Molecular basis of and clinical application of biological markers of bone turnover. Endocr Rev 1996; 17(4): 333–68

    PubMed  CAS  Google Scholar 

  152. Eastell R, Robins SP, Colwell T, et al. Evaluation of bone turnover in type I osteoporosis using biochemical markers specific for both bone formation and bone resorption. Osteoporosis Int 1993; 3: 225–60

    Article  Google Scholar 

  153. Charles P, Poser JW, Mosekilde L, et al. Estimation of bone turnover evaluated by 47Ca-Kinetics: efficiency of serum bone gamma-carboxyglutamic acid-containing protein, serum alkaline phosphatase, and urinary hydroxyproline excretion. J Clin Invest 1985; 76: 2254–8

    Article  PubMed  CAS  Google Scholar 

  154. Moro L, Modricky C, Rovis L, et al. Determinations of galactosyl hydroxylysine in urine as a means for the identification of osteoporotic women. Bone Miner 1988; 3: 271–6

    PubMed  CAS  Google Scholar 

  155. Yoshihara K, Mochidome N, Hara T. Urinary excretion levels of hydroxylysine glycosides in osteoporotic patients. Biol Pharm Bull 1994; 17: 836–9

    Article  PubMed  CAS  Google Scholar 

  156. Nielsen NM, von der Recke P, Hansen MA, et al. Estimation of the effect of salmon calcitonin in established osteoporosis by biochemical bone markers. Calcif Tissue Int 1994; 55(1): 8–11

    Article  PubMed  CAS  Google Scholar 

  157. Sabba AI, Saag KG, Luckey MM, et al. Osteoporosis in 2005: a rheumatology perspective. 2005 Nov 15; CME Consultants Inc.; San Diego (CA)

    Google Scholar 

  158. Kulkarni J, de Castella A, Taffe J, et al. Clinical estrogen trials in patients with schizophrenia. Curr Opin Psychiatry 1999; 12Suppl. 1: 184–5

    Google Scholar 

  159. Halbreich U, Kahn L. Selective estrogen receptor modulators: current and future brain and behavior applications. Expert Opin Pharmacother 2000; 1(7): 1385–98

    Article  PubMed  CAS  Google Scholar 

  160. Crandall C. Combination treatment of osteoporosis: a clinical review. J Womens Health Gend Based Med 2002; 11(3): 211–24

    Article  PubMed  Google Scholar 

  161. Phillips P, Braddon J. Osteoporosis: diagnosis, treatment and management. Aust Fam Physician 2004; 33(3): 111–9

    PubMed  Google Scholar 

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Acknowledgements

The preparation and write-up of this review was not sponsored or supported by any external source of funding. Uriel Halbreich has been a consultant to and received grants from the following pharmaceutical companies: Berlex, Bristol Myers-Squib, Corcept, Eli-Lilly Labs, Janssen, Pfizer, Schering AG, Wyeth Ayerst Inc., Cyberonics and RW Johnson.

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  1. Biobehavior Program, State University of New York at Buffalo, Hayes Annex “C” Ste # 1, 3435 Main Street, Buffalo, New York, 14214, USA

    Uriel Halbreich

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Halbreich, U. Osteoporosis, Schizophrenia and Antipsychotics. CNS Drugs 21, 641–657 (2007). https://doi.org/10.2165/00023210-200721080-00003

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