Serum Prolactin and Bone Mineral Density in Schizophrenia: A Systematic Review

The relationship between serum prolactin and bone mineral density (BMD) in schizophrenia is unclear. We conducted a literature review of databases from inception until December 2018 for cross-sectional, case-control, prospective and retrospective studies analyzing correlations between serum prolactin and BMD measured using dual energy X-ray absorptiometry or quantitative ultrasound at any skeletal site in people with schizophrenia. Data was summarized with a best evidence synthesis. This review identified 15 studies (1 longitudinal study, 10 cross-sectional and 4 case-control studies; 1,360 individuals with a psychotic disorder; mean age 45.1 ± 9.4 [standard deviation] years, female 742 [54.6%], mean illness duration 17.7 ± 11.3 years) assessing the relationship between serum prolactin and BMD in schizophrenia. There was a statistically significant inverse correlation between serum prolactin and BMD identified in eight of the studies (53% of all studies), suggesting mixed evidence for an association between serum prolactin and BMD. Of those studies which identified a significant inverse correlation between serum prolactin and BMD (n = 5), 152 (52.1%) of patients were treated with prolactin raising antipsychotics, compared to 197 (48.1%) of patients in those studies which did not identify a significant correlation between prolactin and BMD. Available studies cannot resolve the link between excess prolactin and reduced BMD in schizophrenia. Future studies should be longitudinal in design and combine measures of serum prolactin along with other risk factors for reduced BMD such as smoking and vitamin D and sex hormone levels in assessing the relationship between prolactin and BMD in schizophrenia.