>>FROM THE EXPERTS

Psychotropic Medication and Osteoporosis

by sylvia r. karasu, m.d.

Osteoporosis is a serious, progressive, and potentially disabling disorder that affects both men and women and can occur at any age, though most commonly it affects the elderly and particularly women after menopause. Signs and symptoms can include back pain; bone fragility due to low bone mineral density; fractures (most commonly at the spine, hip, distal radius, and proximal humerus) that occur without significant accompanying trauma; and deformity.

Osteoporosis is often a silent disease whose first manifestation is a bone fracture. The so-called “gold standard” to measure bone mineral density is dual-energy X-ray absorptiometry (DXA), which is also incidentally one of the most accurate measures of body composition (and specifically our percentage of body fat).

In the United States, it is estimated that approximately 10 million people have osteoporosis, and another 34 million are estimated to have low bone density, that is, osteopenia, that increases their chances of developing full-blown osteoporosis. Osteoporosis can also occur in the context of nutritional deprivation such as seen in those patients with anorexia nervosa who severely restrict their food intake, as well as secondary to chronic diseases such as those of the liver, kidney, and lymph system, organ transplantation, prolonged physical immobilization, and medication intake such as glucocorticoids. Both smoking and excessive alcohol intake have been associated with an increased risk of lowered bone mineral density. Are our psychotropic medications also implicated?

There is a growing body of literature to suggest the answer is, unfortunately, in the affirmative. Both short-term and long-term use of antidepressant medications—predominantly tricyclic antidepressants and selective serotonin reuptake inhibitors (SSRIs)—have been associated with fractures.

In the short-term, within the first weeks of beginning these medications, cardiovascular side effects such as bradycardia and other arrhythmias, orthostatic hypotension, dizziness, and syncope, as well as antihistaminic effects such as sedation and anticholinergic effects such as blurred vision, may lead to physical instability and an increased risk of falls and subsequent fractures, particularly with the tricyclic antidepressants. But after six months of use, it is suggested that medications like the SSRIs can lead to actual decreased bone mineral density. In other words, there is speculation that SSRIs may actually be affecting the “micro-architecture” of bone. The mechanism is not known, but it is likely due to their direct effect on the serotonin transporter system. Studies, though, are complicated due to many possible issues, including how depression is diagnosed across studies that are compared in meta-analyses, as well as to a lack of consistent information on dosages of medications used or even what other medications patients are taking.

Further, there are confounding factors: for example, depression itself may lead to less physical activity, loss of muscle mass, and increased muscle weakness, and depressed patients may have poor nutritional habits that lead to poor intake of calcium and vitamin D, weight loss and lowered body mass index, less sun exposure (also leading to lowered vitamin D levels), and higher intake of both alcohol and tobacco. And as a result of stress, these patients may also have higher levels of 24-hour cortisol and increased catecholamine levels, all of which can affect bone mineral density.

The situation is further complicated because it is not clear whether the association among SSRI use, low bone mineral density, and increased fracture incidence is an example of confounding by indication, that is, when a particular disease and its treatment both have the potential to be associated with the same outcome. For example, depression itself and its resultant consequences of weight loss, decreased activity, and overconsumption of alcohol have all been associated with decreased bone mineral density and increased risk of fractures, as has exposure to its treatment by antidepressants.

As a result, the specific relationship among SSRI use, low bone mineral density, and fracture risk remains unclear (and depends, to some extent, on the particular SSRI used), but a review of the literature that includes observational case-control and cohort-design studies strongly suggests that the use of antidepressant medication, particularly SSRIs, is associated with decreased bone mineral density and bone loss. Older people are particularly more vulnerable to their effects, and hip fractures are the most prevalently reported fractures. Some even suggest that SSRI use may be as detrimental to bone as has been reported with glucocorticoids and that SSRIs should be included in any list of medications associated with osteoporotic fractures. Depressed patients with a history of prior fractures, heavy smoking, and low body mass index, as well as postmenopausal women with depression should be considered candidates for measurement of bone mineral density by DXA scans.

What about antipsychotic medications? It has also been suggested that medications that increase prolactin levels such as risperidone are more likely to decrease bone mineral density than those that are “prolactin-sparing,” such as olanzapine, but patients on antipsychotics may develop reduced bone mineral density through other mechanisms such as decreased exercise, excessive alcohol and tobacco use, and poor nutrition, just as those on antidepressants.

Researchers acknowledge that there is probably not enough evidence yet to recommend routine monitoring of bone mineral density in patients taking antipsychotic drugs, but they do suggest that clinicians have a “lower threshold” for investigating bone mineral density in patients on antipsychotics, especially when patients have additional risk factors for decreased bone mineral density, such as a low body mass index, a history of corticosteroid use, family history of osteoporosis, or a history of previous fractures.

The bottom line is that further studies are warranted, and most researchers believe it is “too early” to suggest that all those on psychotropic medication have DXA testing for bone density. It behooves us as clinicians, though, to discuss with our patients who are on either antidepressants or antipsychotics the possibility that these medications may affect their bone health. Certainly, it is worthwhile to measure calcium and vitamin D levels and, when appropriate, recommend vitamin D and calcium supplementation, as well as recommend supervised exercise for maintaining bone health in those particularly at risk for developing osteopenia and osteoporosis.

Sylvia R. Karasu, M.D., is a clinical professor of psychiatry at Weill Cornell Medical College and senior author of The Gravity of Weight, a comprehensive textbook on the science of weight control, available from American Psychiatric Publishing, which members can order at a discount here.

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