Review articleBipolar disorder and bone health: A systematic review
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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2022, Journal of Psychiatric ResearchCitation Excerpt :In addition, the index of calcium and phosphorus metabolism, such as parathyroid hormone (PTH), vitamin D and its metabolites, calcitonin, calcium, and phosphorus levels reflect the level of bone metabolism (Casado-Díaz et al., 2013). Previous studies have shown that some mental illnesses, including schizophrenia (Stubbs et al., 2014), BD (Chandrasekaran et al., 2019) and major depressive disorder (MDD) (Williams et al., 2009) are related to bone metabolic disease. Since Schweiger et al. first reported in 1994 that patients with MDD had decreased bone mineral density compared with healthy controls (Schweiger et al., 1994), numerous studies have explored the relationship between abnormal bone metabolism and depression.
Bipolar disorder and bone health: A case-control study
2022, Journal of Affective DisordersCitation Excerpt :BD has also been associated with an increased risk of fragility fracture. In a recent systematic review, incorporating three large cohort studies, BD, as defined by hospital records or diagnoses based on DSM or International Classification of Disease (ICD) criteria, was associated with an approximately 20–80% increased fracture risk independent of age, sex, medical comorbidities and medication use (Chandrasekaran et al., 2019). Furthermore, fracture incidence per 1000 person years was greater for those with BD (21.4 per 1000) compared to those without (10.8 per 1000).
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2022, Journal of Affective DisordersCitation Excerpt :Research in Chinese adults found lower bone mineral density at other sites in drug-naïve bipolar disorder patients compared to healthy controls (Li et al., 2020). A 2019 review of three cohorts, one from the US and two from Taiwan, found a higher fracture risk in individuals with bipolar disorder (Chandrasekaran et al., 2019) but included no studies that directly examined bone mineral density. In the present study, we found no evidence of differences in heel bone mineral density between cases and controls.
Associations between major psychiatric disorder polygenic risk scores and blood-based markers in UK biobank
2021, Brain, Behavior, and ImmunityCitation Excerpt :However, it is also possible that fewer associations were detected due to the lower sample sizes employed in the Stahl et al. (2019) GWAS used to determine BD PRS, reducing their predictive power. Nonetheless, we still observed unique associations for BD, including with alkaline phosphatase and calcium, which along with vitamin D are bone health markers, and may relate to bone abnormalities seen in some BD patients (Chandrasekaran et al., 2019). The higher proportion of markers that remained significant after correcting for lifestyle factors may also suggest genetic alterations have a greater influence on the peripheral profile for BD in comparison to MDD and SCZ.
Risk of Hospitalized Falls and Hip Fractures in 22,103 Older Adults Receiving Mental Health Care vs 161,603 Controls: A Large Cohort Study
2020, Journal of the American Medical Directors AssociationCitation Excerpt :Previous research has suggested that anticonvulsant use may be associated with increased risk of any fracture in older veterans with bipolar disorder.64 A previous systematic review of 3 studies suggested that bipolar disorder (at any age) was associated with an increased incidence of any fracture vs the general population.65 Our study advances the field demonstrating the increased risk of falls requiring hospitalization in older adults with bipolar disorder.