The neglected association between schizophrenia and bone fragility: a systematic review and meta-analyses.

Schizophrenia is associated with increased risk of medical comorbidity, possibly including osteoporosis, which is a public health concern due to its significant social and health consequences. In this systematic review and meta-analysis, we aimed to determine whether schizophrenia is associated with bone fragility. The protocol for this review has been registered with PROSPERO (CRD42020171959). The research question and inclusion/exclusion criteria were developed and presented according to the PECO (Population, Exposure, Comparison, Outcome) framework. Schizophrenia was identified from medical records, DSM-IV/5 or the ICD. The outcomes for this review were bone fragility [i.e., bone mineral density (BMD), fracture, bone turnover markers, bone quality]. A search strategy was developed and implemented for the electronic databases. A narrative synthesis was undertaken for all included studies; the results from eligible studies reporting on BMD and fracture were pooled using a random effects model to complete a meta-analysis. The conduct of the review and reporting of results adhered to PRISMA guidelines. Our search yielded 3103 studies, of which 29 met the predetermined eligibility criteria. Thirty-seven reports from 29 studies constituted 17 studies investigating BMD, eight investigating fracture, three investigating bone quality and nine investigating bone turnover markers. The meta-analyses revealed that people with schizophrenia had lower BMD at the lumbar spine [standardised mean difference (SMD) -0.74, 95% CI -1.27, -0.20; Z = -2.71, p = 0.01] and at the femoral neck (SMD -0.78, 95% CI -1.03, -0.53; Z = -6.18, p ≤ 0.001). Also observed was a higher risk of fracture (OR 1.43, 95% CI 1.27, 1.61; Z = 5.88, p ≤ 0.001). Following adjustment for publication bias, the association between schizophrenia and femoral neck BMD (SMD -0.63, 95% CI -0.97, -0.29) and fracture (OR 1.32, 95% CI 1.28, 1.35) remained. Significantly increased risk of bone fragility was observed in people with schizophrenia. This association was independent of sex, participant number, methodological quality and year of publication.

Antipsychotic medication use and fracture: a case-control study.

It has been reported that antipsychotic use is associated with lower bone mineral density and bone quality. We aimed to determine whether antipsychotic use is associated with fracture risk in a population-based sample of adults living in the Barwon Statistical Division, south-eastern Australia. In this case-control study, 1458 participants (51.8% women) with radiologically confirmed fracture between June 1st 2012 and May 31st 2013 (cases) were compared with 1795 participants (46.5% women) without fracture (controls) for the same time period. Medication use, medical history and lifestyle factors were documented by self-report. Multivariable binary logistic regression was used to explore associations between antipsychotic use and fracture following adjustment for possible confounders. In women, antipsychotic use was identified for 20 of 755 (2.6%) cases and 10 of 834 (1.2%) controls (p = 0.034) and in men, antipsychotic use was identified for 13 of 703 (1.8%) cases and 5 of 961 (0.5%) controls (p = 0.010). Following adjustments, antipsychotic use was associated with a 3.0-fold increased risk of fracture in men and a 2.3-fold increased risk of fracture in women. Patterns persisted after exclusion of participants with non-fragility fractures and self-reported schizophrenia. While future research exploring underlying mechanisms is needed, regular monitoring of bone health in antipsychotic users is suggested.

Antipsychotic-induced bone loss: the role of dopamine, serotonin and adrenergic receptor signalling.

Antipsychotics are commonly used in treating psychiatric disorders. These medications primarily target dopamine the serotonin receptors, they have some affinity to adrenergic, histamine, glutamate and muscarinic receptors. There is clinical evidence that antipsychotic use decreases BMD and increases fracture risk, with dopamine, serotonin and adrenergic receptor-signalling becoming an increasing area of focus where the presence of these receptors in osteoclasts and osteoblasts have been demonstrated. Osteoclasts and osteoblasts are the most important cells in the bone remodelling and the bone regeneration process where the activity of these cells determine the bone resorption and formation process in order to maintain healthy bone. However, an imbalance in osteoclast and osteoblast activity can lead to decreased BMD and increased fracture risk, which is also believed to be exacerbated by antipsychotics use. Therefore, the aim of this review is to provide an overview of the mechanisms of action of first, second and third generation antipsychotics and the expression profiles of dopamine, serotonin and adrenergic receptors during osteoclastogenesis and osteoblastogenesis.

Antipsychotic medication use in association with quantitative heel ultrasound (QUS).

Purpose: Antipsychotic medication use has been associated with decreased bone mineral density; however, less is known whether antipsychotics affect other parameters of bone health. Therefore, the aim of this study was to investigate the association between antipsychotic medication use and quantitative heel ultrasound (QUS) in a population based sample of men and women. Methods: Thirty-one antipsychotic users and 155 non-users matched for age and sex were drawn from the Geelong Osteoporosis Study. QUS was undertaken and included the parameters: Broadband ultrasound attenuation (BUA), speed of sound (SOS) and stiffness index (SI). Current medication use, lifestyle factors, anthropometry and socio-economic status were collected. Generalized Estimation Equation models were conducted to determine associations between antipsychotic medication use and each of the QUS parameters, adjusting for covariates. Results: Antipsychotic users were less active, consumed less alcohol, were more likely to smoke and take antidepressants; otherwise, the groups were similar. After adjusting for age, sex and weight, antipsychotic users had a 7.7 % lower mean BUA [108.70 (95 % CI 104.26-113.14) vs. 116.42 (95 % CI 115.48-117.37) dB/MHz, p = 0.005] and 7.4 % lower mean SI [89.92 (95 % CI 86.89-92.95) vs. 97.30 (95 % CI 96.48-98.12) %, p < 0.001] compared to non-users. Differences in mean SOS between antipsychotic users and non-users failed to reach statistical significance (p = 0.07). Conclusion: Antipsychotic use was associated with lower QUS parameters. The risk of bone deterioration should be considered when antipsychotics are prescribed.

Use of antipsychotic medication and its relationship with bone mineral density: A population-based study of men and women.

Background: Schizophrenia has been shown to be associated with reduced bone mineral density (BMD) and higher fracture risk. However, less is known whether antipsychotic treatment is associated with reduced BMD. Thus, we aimed to examine associations between antipsychotic use and BMD among men and women drawn from the general population. Methods: This cross-sectional study involved 793 women and 587 men enrolled in the Geelong Osteoporosis Study (GOS). BMD was determined using dual-energy X-ray absorptiometry at the spine and hip. Information regarding socio-economic status (SES), current medication and/or supplementation use, lifestyle factors, and anthropometry was collected. Association between antipsychotic use and BMD was determined using linear regression after adjusting for potential confounders. Results: Of the group, 33 women (4.2%) and 16 men (2.7%) currently used antipsychotics. Age was identified as an effect modifier in the association between antipsychotic use and BMD for women. Amongst women aged < 60 years, adjusted mean BMD was 11.1% lower at the spine [1.139 (95%CI 1.063-1.216) vs. 1.250 (95%CI 1.223-1.277) g/cm2, p = 0.005] for antipsychotic users compared to non-users. At the hip, age, weight, and smoking adjusted mean BMD was 9.9% lower [0.893 (95%CI 0.837-0.950) vs. 0.992 (95%CI 0.976-1.007) g/cm2, p < 0.001] for antipsychotic users in comparison with non-users. The pattern persisted following further adjustments. There was no association detected between antipsychotic use and BMD for women aged 60 years and over and for men. Conclusion: Our data suggest that antipsychotic medication use is associated with reduced BMD in younger women but not older women or men.

Relationship between adverse childhood experiences and Alzheimer's disease: a systematic review and meta-analysis protocol.

INTRODUCTION: Alzheimer's disease has a high prevalence and a substantial impact on society, as well as the individual. Findings from clinical studies to date, suggest that multiple factors are likely to contribute to the variability seen in the progression of Alzheimer's disease. However, despite this accumulating evidence, current identified factors do not explain the full extent of disease onset. Thus, the role of additional factors needs to be explored further.One such factor is exposure to adverse childhood experiences. However, the degree of this association is unknown. This systematic review will examine the literature investigating the associations between adverse childhood experiences and the risk of Alzheimer's disease. METHODS AND ANALYSIS: Articles investigating associations between exposure to adverse childhood experiences and the risk of Alzheimer's disease will be identified systematically by searching CINAHL, MEDLINE and PsycInfo using Ebscohost. No restrictions on date of publication will be applied. The search strategy will be built combining the main key elements of the Population, Exposure, Comparator, and Outcomes inclusion criteria. A meta-analysis is planned and statistical methods will be used to identify and control for heterogeneity, if possible. The development of this protocol was guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols. ETHICS AND DISSEMINATION: Only published data will be used for this study, thus, ethical approval will not be required. Findings of the review will be published in a peer-reviewed scientific journal, and presented at national and international conferences. PROSPERO REGISTRATION NUMBER: CRD42020191439.

Study protocol for the systematic review and meta-analyses of the association between schizophrenia and bone fragility.

INTRODUCTION: Individuals with schizophrenia are known to be at higher risk of comorbid conditions, both physical and psychological. Osteoporosis is possibly one of these, leading to public health concerns due to higher rates of associated mortality and morbidity. We aim to systematically search all available evidence across electronic databases regarding the relationship between schizophrenia and bone fragility. METHODS AND ANALYSIS: A systematic search of the research databases CINAHL, MEDLINE Complete, Embase and PsycINFO will be conducted and identified papers reviewed for eligibility, with a second reviewer confirming inclusions. Searches will be run from database inception to 1 October 2020 and supplemented by the hand checking of references of identified articles. A previously published scoring system will be used for assessing the methodological quality and risk of bias. A meta-analysis is planned. ETHICS AND DISSEMINATION: Due to including published literature only, ethical permission will not be necessary. Results of this study will be published in a relevant scientific journal and presented at a conference in the field of interest. PROSPERO REGISTRATION NUMBER: CRD42020171959.