Introduction
It has previously been shown that patients taking antipsychotic medications are at greater risk for bone fractures [
1]. The onset of schizophrenia typically occurs during adolescence and young adulthood [
2], therefore, the administration of antipsychotic medications generally begins during the same period, during which bone maturation results in peak bone mass.
In previous studies that have considered decreased bone mass in patients with schizophrenia, factors associated with accelerated bone absorption have included polydipsia [
3], use of neuroleptics [
4] and the resulting hyperprolactinemia [
5,
6], heavy smoking [
7], poor diet, drug and alcohol abuse [
8], and lack of exercise [
9].
However, to date there have been a limited number of studies [
10‐
12] comparing bone mass between patients with schizophrenia and the general population. It is therefore necessary to accurately examine the nature of bone mass deficiencies in schizophrenic patients in a cross-sectional manner with an age-matched healthy control group for comparison.
In recent years, a quantitative ultrasound (QUS) densitometry technique has been developed for measuring bone mass. The results obtained using QUS are reported to correlate well with those using dual energy x-ray absorptiometry (DXA) [
13]. Furthermore, QUS can provide data on the risk for osteoporosis related fractures [
14,
15]. QUS is a relatively quick procedure that is inexpensive and does not expose patients to radiation, making it suitable for research projects examining large numbers of subjects [
16].
The aim of this study was to compare bone mass between patients with schizophrenia and healthy individuals using QUS. To the best of our knowledge, this is the largest study of this nature to be carried out in Japan.
Discussion
This study was designed to evaluate the effects of age and disease on bone mass in patients diagnosed with schizophrenia. In both males and females, schizophrenic patients had lower bone mass than that of the general population in age groups of 60 years and older. A descending trend between mean OSI value and age was observed in both genders in the schizophrenic patients and in the community group. However, a significant interaction between subject group and age in general linear model showed that descending trend of OSI value with aging was accelerated in male schizophrenic patients.
Several previous studies have compared bone mass between schizophrenic patients and the general population. In a large Taiwanese study, Renn
et al. [
11] reported that 965 schizophrenic patients had lower bone mass values than those observed in the general population under the age of 50 in both genders. However, bone mass was higher in schizophrenic patients over the age of 60 than in the general population in both genders, indication that an aging effect on bone mass was not observed in schizophrenic patients. However, Kishimoto
et al. [
10] reported that bone mass among 74 male schizophrenic patients was lower than in the general population in the age group of 40 to 49 and 55 to 79. Furthermore, Jung
et al. [
12] also reported that 229 schizophrenic patients over age 50 had a higher prevalence of osteoporosis than healthy controls. In addition to the comparison studies with the general population, Liu-Seifert
et al. [
21] reported that low bone mineral density (BMD) was significantly associated with age in both genders among schizophrenic patients.
One possible explanation for the discrepancies observed regarding aging effects on bone mass among older schizophrenic patients is that those with the greatest bone fracture risk may expire at a relatively young age, leaving a cohort of survivors in the patient group over 60 years of age in the Taiwanese study. Another possible explanation is that the location from which the patients and controls were recruited differed in the Taiwanese study. In the current study, we recruited both patients and controls from the Aomori prefecture to rule out any geography-related effects.
In this study, the trend relating OSI value and aging among schizophrenic patients does not differ from that in the general population in females. One possible explanation is that the effects of menopause on bone loss might exceed those of antipsychotic medication or the disease itself. Estrogen deficiency at menopause leads to increased skeletal remodeling and loss of bone mass [
22]. A decrease in estrogen levels can influence the activity of interleukins, which are known to influence dynamic bone homeostasis [
23]. The protective effect of estrogen to bone mass might explain the earlier decline of bone mass among male schizophrenic patients than female ones. Another possible explanation is that secretion of estrogen or leptin from stored bodily fat might protect bone loss in female patients with schizophrenia, as these patients have more body fat [
24,
25] than the general population. Previous studies [
26,
27] have additionally shown a relationship between fat mass and bone mineral density among females.
The mechanism for decreased bone mass among patients with schizophrenia has not been entirely elucidated. However, most antipsychotics block dopamine-D2 receptors, attenuating the inhibitory effect of dopamine on prolactin release from the pituitary gland and resulting in hyperprolactinemia [
28]. Previous studies have shown that patients who are treated with antipsychotics have elevated prolactin levels [
6,
29], which is correlated with decreased bone mass in schizophrenic patients. Even when a direct effect of prolactin on BMD was not observed, the duration of antipsychotic treatment had a tendency to be associated with decreased BMD [
30], and patients with hyperprolactinemia showed higher rates of bone metabolism, including both bone formation and resorption [
5].
The present study has some limitations. First, measurement of bone mass was based on QUS densitometry instead of DXA scans. There are many researchers who question the precision of peripheral bone mineral density measurements. Previous studies have reported that QUS parameters cannot be used to predict decreased BMD and that the sensitivities and specificities of QUS parameters are not sufficient to allow it to be used as an alternative to DXA [
31‐
33], which is currently the gold standard for measuring BMD [
34,
35]. However, most psychiatric clinics do not have access to DXA equipment and DXA scanning is time consuming, costly and exposes patients to radiation, rendering it less than ideal for a large population survey. In contrast, QUS is rapid and portable, making it a suitable method for large studies. For these reasons, we chose to use this method for our study. Second, because all participants of patients and control consisted of volunteers, they may have more interests in their health or be healthier than the outpatient population or general population. Third, not all parameters which could affect bone mass were included in this study such as body mass index, dietary habits, smoking, alcohol intake, physical exercise, duration of illness and treatment, schizophrenic symptoms and medications. Antipsychotic medications in particular may be an important factor, as the use of prolactin-sparing or prolactin-raising antipsychotics might confound the results. Future research should endeavor to consider the effects of drug treatment and lifestyle factors in conjunction with decreased bone mass in schizophrenia.
Competing interests
The authors declare that they have no competing interests.
Authors' contributions
NS conceived the study, designed the study, conducted the statistical analysis, interpreted the data and wrote the initial draft of the manuscript. SK and NYF had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. ST, YS and MS contributed to study design and assisted in drafting the manuscript. AF and HF completed initial survey construction, recruitment of participants. TU, IT, MM and KD participated in the data collection, and the interpretation of the results. All authors approved the final manuscript.