Elsevier

Journal of Affective Disorders

Volume 249, 15 April 2019, Pages 262-269
Journal of Affective Disorders

Review article
Bipolar disorder and bone health: A systematic review

https://doi.org/10.1016/j.jad.2019.02.013Get rights and content

Highlights

  • This systematic review explored a novel and covert clinical area.

  • Two authors independently confirmed study selection, and undertook data extraction and methodological assessment. Where necessary, a third author provided final judgement.

  • Heterogeneity and the paucity of data, prevented a meta-analysis. Therefore, a ‘best evidence synthesis’ was carried out.

  • Three cohort studies investigating associations between bipolar disorder and bone health in adults were identified, and comprehensively assessed for methodological quality. Potential confounders of the association between bone and bipolar disorder were identified, and our findings were synthesised accordingly.

  • Fracture risk was reported to be higher for those with bipolar disorder compared to those without, independent of age, sex and comorbidities.

Abstract

Background

Bipolar disorder is a chronic, episodic mental illness, affecting around 2.4% of the population worldwide. Psychological and/or physiological comorbidities are a common consequence, and osteoporosis is one such possible comorbidity. Thus, this systematic review aimed to collate, evaluate, and discuss the literature examining the link between bipolar disorder and bone health.

Methods

We conducted an e-search of PubMed/OVID/MEDLINE, PsychINFO and CINAHL to identify studies that investigated associations between bipolar disorder and bone in adults aged ≥18. Two reviewers determined eligibility according to pre-determined criteria, and methodological quality was assessed using a previously published methodological scoring system. Due to heterogeneity, a best-evidence synthesis was performed.

Results

Our search yielded 1409 articles, of which three (all cohorts) met predetermined criteria. The studies from Taiwan and the United States of America analysed administrative data, albeit spanning different years, and comprised a total of 344,497 participants. No studies investigating bone quantity or quality were identified. Bipolar disorder was associated with an increased risk of fracture (range 20–80%); and fracture-free survival time for those with bipolar disorder decreased substantially with advancing age, and for women (10–30% shorter than men). Fracture incidence per 1000 person years (py) was 21.4 and 10.8 in those with and without bipolar disorder, respectively.

Limitations

Limited data and marked methodological heterogeneity prevented the pooling of these data for a numerical synthesis.

Conclusions

Increased fracture risk was observed in individuals with bipolar disorder, independent of older age, sex, comorbidities and medication use. The operative mechanisms, risk and treatment factors warrant further enquiry.

Introduction

Bipolar disorder is a leading cause of years lived with disability in the world (World Health Organisation, 2003). Aside from psychological comorbidities, non-communicable physical disorders are common across psychiatric illnesses (Sanna et al., 2013). Poor bone health is no exception, with recent data showing associations between unipolar depression and reductions in bone mineral density (BMD) and increased fracture risk in men and women across the lifespan (Cizza et al., 2010, Fernandes et al., 2016, Williams et al., 2016). A research synthesis with meta-analyses concluded that major depression should be considered a risk factor for osteoporosis onset that is as powerful as recognised risk factors such as smoking, physical inactivity and inadequate calcium nutrition (Cizza et al., 2010). Mezuk, 2008

A review from 2008 alluded to the possibility that bipolar disorder, associated lifestyle factors and/or the medications commonly used to treat the disorder, could also be detrimental to bone health (Mezuk, 2008). The lifetime risk for hip, vertebral and wrist fractures alone has been estimated to be approximately 40% (World Health Organisation, 2003). Fractures contribute to loss of independence, limited mobility, chronic pain and an overall increased mortality rate (Murray and Lopez, 1996, Otmar et al., 2013, Williams et al., 2011); the direct and indirect costs of osteoporosis, osteopenia, and the resulting fractures between 2012–2022 is estimated to be $33.6 billion in Australia (Watts et al., 2013), with similar studies showing the growing economic impact of osteoporosis worldwide (Cauley, 2013, Hernlund et al., 2013).

In order to add to the growing evidence base studying this association, this systematic review aims to collate existing data regarding the association between bipolar disorder and bone health.

Section snippets

Methods

The published protocol for this systematic review (Chandrasekaran et al., 2017) is registered with the International Prospective Register of Systematic Reviews (PROSPERO) (CRD42017074372).

Methodological quality and heterogeneity

During the methodological quality assessment, an initial inter-rater reliability of 91.7% was achieved, and all discrepancies were resolved after one consensus meeting and consultation with the third reviewer (SLB-O). The overall mean score of methodological quality was 77.8% (range 75.0–83.3%). Given the small number of studies included in this review, all studies were included in the best-evidence synthesis.

Heterogeneity tests, determined using RevMan, revealed that whilst methodological

Discussion

This systematic review identified and evaluated the largely understudied area of research investigating the association between bipolar disorder and bone health. Fracture risk was reported to be higher for those with bipolar disorder compared to those without, independent of age, sex, comorbidities and medication use.

These findings contribute to the previous literature, suggesting unipolar depression is associated with increases in fracture risk (Williams et al., 2016). Unipolar depression has

Conclusion

According to the objectives stated in our published protocol (Chandrasekaran et al, 2017), we systematically identified published literature investigating the association between bipolar disorder and bone health, and evaluated the methodological quality of the identified studies. We also discussed the known potential confounding and/or mediating factors in our review. However, owing to the heterogeneity between the identified studies, the data could not be pooled for a numerical synthesis.

Author statement

VC, LW and SLB-O developed the e-search strategy. VC conducted the exclusions, which were confirmed by ALS. LJW and ALS conducted the methodological scoring. SLB-O and VC performed data extraction. All authors edited, revised and approved the methodological processes. VC, SLB-O and LJW drafted the manuscript, and all authors edited and contributed to the writing of this paper. All authors read and approved the final version, and guarantee the review.

Acknowledgements

We would like to acknowledge Ms. Sophia Xin Sui for her assistance in translating the title of an article written in Chinese. We also thank Associate Professor Seetal Dodd for his support in translating the abstract of an article published in French.

Funding

The study is supported by the National Health and Medical Research Council (NHMRC, of Australia) (GNT1104438). V.C. is supported by a Deakin University Postgraduate Research Scholarship, S.L.B-O and L.J.W. are each supported by a NHMRC Career Development Fellowship (GNT1107510, and GNT1064272, respectively), and M.B. is supported by a NHMRC Senior Principal Research Fellowship (GNT1059660).

Conflict of interest

None of the authors have any relevant conflicts of interest related to the work under consideration for publication. S.L.B-O has received Honorarium fees from Amgen Australia and Pfizer Australia, and Grant/Research support from the University of Melbourne, Deakin University, Arthritis Victoria, Arthritis Australia, Australian Association of Gerontology, and the City of Greater Geelong. J.A.P. has received speaker fees from Amgen, Eli Lilly and Sanofi-Aventis and funding from the Geelong Region

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