Osteoporosis and depression

“Depression may increase the risk of the bone disorder osteoporosis in premenopausal women,” BBC News reported today. The report describes a study that compared depressed women with non-depressed women aged 21 to 45. It found that the risk of the bone disorder, osteoporosis, is significantly increased in those who are depressed.

The authors of the study suggest that depressed women have overactive immune systems that make too many inflammatory chemicals, one of which actually promotes bone loss. BBC News quotes them as saying "now we know that depression can serve as a red flag - that depressed women are more likely than other women to approach menopause already at higher risk of fractures".

Although this was a small study in young women, the finding is important as there are a large number of people who suffer from both these conditions. The study looked at women with osteopenia (thin bones) rather than full osteoporosis and used a broader definition of what classifies as osteopenia than that given by the World Health Organisation (WHO). As there are many “lifestyle factors” associated with both conditions, by understanding the links between the diseases and the risk factors, the detection of osteoporosis may be increased by looking for the condition in “at risk groups”.

Where did the story come from?

Dr Farideh Eskandari and colleagues conducted the research. They are all members of the study group: Premenopausal, Osteoporosis Women, Alendronate, Depression (POWER), and mostly from Cleveland, Ohio or Bethesda, Maryland in the USA. The study was supported in part by several programmes and centres of the National Institutes of Health.

The study was published in the peer-reviewed medical journal:  Archives of Internal Medicine.

What kind of scientific study was this?

This was a case-control study that used participants selected from a large ongoing cohort study that has not yet reported its main results.

The researchers compared the bone mineral density (BMD) of 89 pre-menopausal women with major depression to 44 healthy control women (aged between 21 and 45). They excluded women who were at risk of suicide or who had hyperthyroidism, vitamin D deficiency or other treatments or diseases that could affect bone turnover. The depressed women were similar to the controls for intakes such as smoking, calcium, caffeine and alcohol.

All women had a range of blood tests and a psychiatric assessment that used a structured interview to assess the severity of depression using recognised scoring scales.

Bone mineral density (BMD) was measured by dual-energy x-ray absorptiometry (DEXA scanning) using the standard technique at four sites: the lumbar spine, femoral neck (part of the hip) the total hip and the mid distal radius (forearm near the wrist).

The researchers defined low BMD as having a T-score (bone density compared to what is normally expected from a healthy young adult of the same sex) of less than minus one. The WHO defines normal bone density to be within one standard deviation of the young adult mean i.e. T-score greater than -1. Osteopenia (the thinning of bones) is defined as having a T-score between -1 and -2.5. Osteoporosis is usually defined as a T-score less than -2.5.

The authors also examined blood tests for a specific type of protein (called a cytokine) secreted by cells involved in immune and inflammatory responses. These they thought might be involved in the pathway as an explanation of how depression causes thinning of the bones.

What were the results of the study?

The proportion of women with a low hip (femoral neck) bone mineral density was significantly greater in those with major depression than the controls without depression (17% versus 2%) and for the total hip (15% versus 2%).

There was a trend towards lower bone mass in the lower back (lumbar spine), and this was found in 20% of depressed women compared to only 9% of non-depressed women. However, this result was not statistically significant.

Women with major depression also had increased levels of pro-inflammatory cytokines and decreased levels of anti-inflammatory cytokines.

What interpretations did the researchers draw from these results?

The researchers interpret these results as an observation of lower BMD, and an increase in pro-inflammatory cytokines in premenopausal women with major depression.

They say this implies that the risk of fracture may be increased in women with major depression, especially after the onset of menopause, though they did not measure this directly. Given that depression is a common chronic condition and that thinning of bones (osteopenia) is often “clinically silent” (without signs or symptoms), they claim that their sample may be representative of a large population in whom osteopenia remains undiagnosed until the time of fracture. This, they say, supports the claim that major depression “should be formally recognised as a risk factor for low BMD in premenopausal women.”

What does the NHS Knowledge Service make of this study?

This study has several strengths that the authors refer to;

• It only enrolled people with a current or recent history of depression using a structured interview and recognised criteria of major depression. This will have avoided some of the “recall bias” that may come from having to ask people to remember accurately aspects of events that happened in the past.
• The participants were drawn from a community sample, which is also an advantage as this increases the possibility that they were representative of most women with major depression or osteopenia .Bias could have been introduced If the women were recruited form hospital wards for example.

The authors admit that it is not possible to state that the observations were not a result of the participants’ use of medication (34% of women in the depression group were taking medication). There is a possibility that these drugs could affect BMD and may have affected the results of the study.  In addition, the risk factors for osteoporosis, such as smoking, exercise and calcium intake were only investigated once at the start of the study and may not accurately reflect what happened over an individual’s lifetime. It is possible that patients did not accurately recall their risks.

Overall, this study has demonstrated a link that will need further investigation in larger studies that follow people over time. The authors report that these have already commenced.