Is there a nexus between mental and bone health?

The scope of the problem

Osteoporosis and psychiatric disorders share the distinction of being prevalent and disabling public health problems. There is some evidence suggesting that the prevalence of depression is rising in western countries and equally, consequent to the ageing of western societies, the burden of osteoporosis is also predicted to rise. These disorders arguably co-segregate more commonly than would be expected by chance. This interrelationship between psychiatric disorders and low bone mineral density (BMD) has been shown in depression and schizophrenia, across the age spectrum, in males and females and in western and non-western countries (Fernandes et al., 2016; Kishimoto et al., 2012). Unfortunately, treating psychopathology is not necessarily a pathway to optimal bone health. There is now abundant evidence suggesting that psychotropic agents have deleterious effects on bone (Fernandes et al., 2016). Currently, safety monitoring guidelines for mood and psychotic disorders do not emphasise monitoring for bone health despite this nexus.

There is a striking paradox in terms of age. The consequences of low BMD are predominantly evident in older individuals. Yet, the seeds of this problem are sown early in life. Not only is there rapid bone accrual in adolescence, but this is the age of onset of most major psychiatric disorders, as well as a time period where many of the shared environmental risk factors for bone and mental health operate. There is evidence that in adolescent cohorts, a reduction in BMD is already evident among those with depression, and they are more likely to manifest risk factors for both depression and low BMD such as smoking. It is thus critical, since we have become aware of this problem, that we actively seek to recognise this co-morbidity and begin to manage it actively while it remains amenable to intervention.

Pathways and mechanisms

With regards to lifestyle factors, many of the risk factors for psychiatric disorders and poor bone health overlap. Well-known risk factors for osteoporosis include smoking, alcohol, physical inactivity, stress, sleep deprivation, vitamin D insufficiency and medications such as glucocorticoids. Environmental risk factors for mood, anxiety and psychotic disorders similarly include poor diet, smoking, alcohol and other substance abuse, physical inactivity, distal and proximal stressors, sleep deprivation, vitamin D insufficiency, medical co-morbidity and genetic risk factors. In terms of the operative biochemical pathways, critically overlapping risk pathways include inflammatory cytokines such as C-reactive protein, leptin and oxidative stress.

There is now a growing body of epidemiological evidence suggesting that psychotropic agents have deleterious effects on bone in both men and women and across the age range. Perhaps, the first psychotropic agents for whom deleterious effects on bone were evident were anticonvulsants such as valproate and carbamazepine. Although it is now clear that the antidepressants, such as selective serotonin reuptake inhibitors (SSRIs), have adverse effects on bone, this effect is shared by many antipsychotic agents (Fernandes et al., 2016). A point of considerable clinical importance is that even within classes of psychotropic agents, there seems to be significant divergence in terms of effects on bone. As an exemplar, within the SSRIs there appears to be a rank order of bone toxicity, with sertraline and fluoxetine potentially being more toxic than citalopram (Hodge et al., 2013). The mechanisms whereby these effects are mediated are unclear. With regard to antipsychotics, a prominent hypothesis has been the mediating role of prolactin, although first, this is not fully supported by the extant literature and second, other pathways such as the monoamines themselves and apoptosis and related pathways appear to have important effects. Many monoamines have their receptors expressed on osteoblasts and osteoclasts and clearly have important signalling roles in those tissues (Warden and Haney, 2008). It is evident that a better understanding of the mechanistic pathways whereby these agents affect bone turnover and function will be critical in clinical management of these adverse effects.

Clinical implications and next steps

Given that many of the environmental risk factors are shared, a sensible place to start is active management of health risk behaviours including smoking, physical inactivity, poor diet and vitamin D insufficiency. If data are borne out that there are significant within class differences between psychotropic agents, these differences may serve as a critical factor in treatment selection within a given therapeutic path. If it is true that there is a clinically meaningful co-morbidity between mental health and bone health and that these problems are potentially worsened by psychotropic treatments, then the issue of screening at-risk populations becomes evident. Currently, the standard screening technique is radiographic dual energy X-ray absorptiometry, which has implications in terms of cost and exposure to ionising radiation. Some authors have proposed the use of non-invasive, quantitative heel ultrasound as a non-invasive and cheap screening tool suggesting that it may be a viable alternative for screening at-risk populations (Williams et al., 2013). Nevertheless, immediate attention needs to be given to filling the gaps in the evidence base, so that appropriate recommendations can be made.