Older people are more likely to suffer a fall and with an ageing population, hip fractures are a growing issue. And new research suggests that the impact of a fall may speed up frailty.
The factors influencing recovery after a hip fracture are poorly understood, but we now know that depression is common and is associated with increased risk of infections and an inability to regain previous levels of physical functioning.
We sought to test the hypothesis that psychological distress - specifically depressive symptoms that emerge after hip fracture - combined with physical stress amplifies the effect of ageing on a patient’s immunity and physical frailty.
Stress, age and risk
When we age, our immune system changes which contributes to a higher risk of infection. Evidence suggests that the effects of stress and age are interactive, with chronic stress also worsening the effects of ageing.
A previous study we carried out in older adults showed that individuals who had been exposed to stressful life events, such as bereavement and marital dissatisfaction, had lower antibody responses to vaccination.
Neutrophils are key immune cells; they neutralise bacterial pneumonia, for example, a common cause of death in older adults, and infections, particularly after hip fracture. But neutrophils' ability to kill bacteria through a process called superoxide generation is also reduced in older hip fracture patients and bereaved older adults.
Cortisol is the key stress hormone in humans that increases in response to psychological and physical stress. But it can also suppress immunity. Another steroid hormone, dehydroepiandrosterone sulphate (DHEAS), has been reported to have anti-depressive and immune-enhancing properties.
When we age, the balance between these hormones changes, leaving us with a higher ratio of cortisol to DHEAS. This could be further heightened by chronic stress, as happens with hip fracture. Cortisol levels are also often higher in individuals with depression. And high cortisol and lower DHEAS levels in older adults has been associated with physical frailty.
This hormone balance may be a major determinant of frailty in older hip fracture patients, as well as their susceptibility to infections, and particularly in those with depression.
Accelerating the effects of ageing
Some people are more prone to developing depression in the face of a stressful event, but we were interested in those who developed it after the physical trauma of hip fracture but who had never experienced depression before. It’s the first time these patients have been studied in this way.
We recruited 101 people (81 female) older than 60 who had been admitted to a West Midlands hospital with a fractured hip. All completed questionnaires, structured interviews and provided a blood sample six weeks and six months after their fracture. Another 50 healthy older adults who hadn’t broken their hip were also recruited as control participants. We conducted same-day analysis of neutrophil phagocytosis (its bacteria-eating ability) and neutrophil superoxide production (its bacteria-killing ability) and froze the remainder of the samples to measure for hormones.
Participants' psychological states were also assessed using standard measures for depressive symptoms, and during daily living activities (for example washing and cooking). We also assessed walking ability, handgrip strength and balance. On the basis of their depression scores, patients were classified into two groups; 38 (37%) of the hip fracture patients had depressive symptoms six weeks after their fracture. By six months, 66 hip fracture patients were still participating in the study, and of those 19 (29%) were depressed.
Depression and recovery
Neutrophils' ability to kill bacteria differed between the groups, but significant impairment happened only in the hip fracture patients who had developed depressive symptoms. This means that depressed hip fracture patients are less likely to be able to ward off infections like pneumonia.
Patients with symptoms of depression were less able to engage in activities of daily living than non-depressed patients and took significantly longer to complete a walking speed test at follow-up. They also scored significantly worse on the Berg balance scale, used to measure balance in older people with impairment, at week six compared to non-depressed patients, and they spent a significantly longer in hospital and/or rehabilitation centres.
Hip fracture patients with depression also had a much higher cortisol:DHEAS ratio than the other groups. In our study the higher the depression score, the higher the ratio. However, the hormone ratio was not related to neutrophils' bacteria killing ability, suggesting that it is not the main cause of impaired immunity. It was related to walking speed at month six and the higher the ratio, the longer it took the participant to walk three metres. This suggests that this hormone ratio may have a role to play in the progression of physical frailty.
Possible new treatment
Our findings support the need to identify and treat depressive symptoms in people who have suffered a hip fracture. Anti-depressants are inadvisable for those with existing osteoporosis. But the link with the cortisol:DHEAS ratio suggests a different intervention; adjusting this ratio to help recovery.
DHEA hormone tablets, given as a nutritional supplement, have been effective at increasing wellbeing and mood and improving physical function. Although some studies have shown limited effectiveness in healthy populations, we believe the real effects of DHEA supplementation will be seen among people with a high ratio of the two hormones, such as in our older depressed hip fracture patients. And they would be cheaper than developing a new anti-depressant or psychological therapies.