Effects of psychiatric disorders and psychotropic medications on prolactin and bone metabolism

Objective: Osteoporosis occurs in common psychiatric conditions and causes significant morbidity. Many neuroleptic medications can cause hyperprolactinemia, which can then potentially be associated with bone loss. Few reviews have thus far addressed this issue. We have consolidated information from studies that examined effects of psychiatric conditions and their treatment on bone metabolism. Data Sources: We searched PubMed for original articles and reviews published between 1976 and 2004 that described changes in bone metabolism in psychiatric disorders and examined prolactin elevations with neuroleptic medications. Keywords used were major depressive disorder, bipolar disorder, schizophrenia, bone density, bone metabolism, hyperprolactinemia, typical antipsychotics, and atypical antipsychotics. Study Selection and Data Extraction: 160 articles published in peer-reviewed journals were identified and are summarized, with greater emphasis given to data from larger, controlled studies. Data Synthesis: Schizophrenia and major mood disorders are often associated with perturbations in bone metabolism related to factors including nutritional alterations, smoking, and hypogonadotropic hypogonadism, with or without medication-induced hyperprolactinemia. Polydipsia can contribute to bone loss in schizophrenia, whereas hypercortisolemia is often associated with low bone density in depression. Lithium in bipolar disorder and thyroid-stimulating hormone-suppressive doses of L-thyroxine have a negative impact on bone health. Mood stabilizers such as carbamazepine and valproate can also affect bone density. Hyperprolactinemia may lead to bone loss only if associated with untreated amenorrhea in women or testosterone deficiency in men. Some atypical neuroleptics, by causing lesser elevations in prolactin, may therefore have a less marked impact on bone than typical neuroleptics. Conclusions: Because significant morbidity is associated with low bone density and many psychiatric conditions may have a negative impact on bone metabolism, bone density evaluation should be considered an integral component of chronic medical care of these disorders, and risk factors should be identified and addressed.