Relationship between antipsychotic medication, serum prolactin levels and osteoporosis/osteoporotic fractures in patients with schizophrenia: a critical literature review

ABSTRACT

Introduction: Using an antipsychotic medication can increase prolactin (PRL) levels, causing hyperprolactinemia (HPRL). Although the occurrence of osteoporosis within the population of patients with schizophrenia has been recognized, the precise nature of the association between antipsychotic treatment, PRL, osteoporosis, and the disease itself seems to be elusive.

Areas covered: The aim of this review is to critically review the literature regarding the association between osteoporosis and PRL and to summarize the available evidence with respect to the impact of PRL-elevating antipsychotics on bone mineral density (BMD) and fractures in non-elderly patients with schizophrenia.

Expert opinion: Although long-standing HPRL can have an impact on the rate of bone metabolism and, when associated with hypogonadism, may lead to decreased bone density in both female and male subjects, the relative contribution of antipsychotic-induced HPRL in bone mineral loss in patients with schizophrenia remains unclear. Methodological shortcomings of existing studies, including the lack of prospective data and the focus on measurements of BMD instead of bone turnover markers, preclude definitive conclusions regarding the relationship between PRL-raising antipsychotics and BMD loss in patients with schizophrenia. Therefore, more well conducted prospective trials of these biomarkers are necessary to establish the precise relationship between antipsychotics, PRL levels and osteoporosis/osteoporotic risk.

KEYWORDS:

• Hyperprolactinemia
• schizophrenia
• antipsychotic
• prolactin
• osteoporosis
• fracture

Article highlights

• A low-to-moderate increased risk of osteoporosis and osteoporotic fractures compared with the general population is reported in patients with schizophrenia treated with antipsychotic medication. However, the question that antipsychotic medications are a causal factor in falls and fractures remains to be elucidated.

• Although antipsychotic-induced HPRL has been suggested as one of the mechanisms of low BMD in schizophrenia, results are mixed and firm conclusions cannot be drawn at this point, due to an inconsistent pattern of results and methodological shortcomings.

• More well-designed, prospective studies, particularly of bone turnover markers, are needed, in order to better examine the relationship between antipsychotics, osteoporosis, and osteoporotic fractures.

• Unhealthy lifestyle behaviors, such as little or no exercise, alcoholism, smoking, undernutrition, and unhealthy diet with deficiencies of calcium and vitamin D, neurochemical and functional abnormalities due to the disease probably contribute more to low BMD and elevated fracture risk in schizophrenia.

This box summarizes key points contained in the article.

Declaration of interests

M De Hert declares that he has been a consultant for, received grant and/or research support and honoraria from, and has been on the speakers’ bureaus and/or advisory boards of the following companies: Janssen-Cilag, Lundbeck and Takeda. J Detraux declares that his work for the Belgian Discussion Board on Antipsychotic Treatment, established by Janssen and consisting of Belgian psychiatrists discussing relevant topics on antipsychotic treatment, has been partially supported by the Janssen Academy. No sources of funding were used to prepare the review. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed