Bone Mass Density Loss and Antidepressants: Another Tough Break for SSRI Users?

A study by Richards and colleagues⁸ focused more directly on fracture risk than BMD loss. These investigators compared the incidence of fractures among SSRI users and nonusers in a prospective cohort of 5008 community-dwelling adults aged 50 or older over a 5-year interval in the Canadian Multicentre Osteoporosis Study. Most of these patients also had lumbar spine and hip BMD measurements. Estrogen and SSRIs were the most frequently used medications by these patients. Daily SSRI use was associated with a 2-fold increase in fracture risk and significantly lower total hip BMD measures. The effect of depressive symptoms, as assessed with scales of the Medical Outcomes Study ShortForm–36, was controlled for in this study.

Hypothetical mechanisms for the effects of SSRI on BMD include a reduction in osteoblast activity resulting from serotonin transporter inhibition or a reduction in remodeling resulting from SSRI interference with osteoclast differentiation.⁶ This direct serotonergic effect differs from any of the several proposed mechanisms used to explain the well-documented BMD loss associated with depression (Table 3). It is conceivable and consistent with the findings of Diem and colleagues⁷ that BMD loss associated with depression and SSRI use might even be additive in some patients, although successful treatment of depression might decrease the depression-related component of BMD loss. No study has compared the magnitude of the effects of SSRIs and depression on bones, and I could locate no study that addresses serotonin norepinephrine reuptake inhibitor (SNRI) effects on BMD, although the SNRIs’ serotonergic effects certainly raise the possibility of a similar BMD reduction risk.

Effects of findings on treatment

How should this information about osteoporosis affect the practice of a prudent (and alliterative) psychiatrist? As summarized in Table 4, risk assessment is relatively quick and simple thanks to readily available assessment resources. These include the World Health Organization’s fracture risk algorithm (FRAX, an interactive Web-based, printable assessment tool available at www.shef.ac.uk/FRAX) or the very patient-friendly Web site “Tone Your Bones,” offered through the Osteoporosis Prevention and Treatment Clinic at the University of Alabama at Birmingham (www.toneyourbones.org). The latter Web site also offers advice about intake of calcium and other nutrients, attention to dietary factors that affect bone, a list of medications implicated in BMD loss, suggestions regarding bone-strengthening physical exercises, and lucid discussion of the available medications that prevent or palliate osteoporotic bone changes (including the pros and cons of hormone replacement therapy and the use of oral bisphosphonates and the parathyroid hormonelike, teriparatide).

We can promote osteoporosis awareness among our patients and direct them toward screening or further assessment in primary care, particularly among at-risk persons and women aged 65 or older who have not already been screened.¹⁰ Osteoporosis medications can be included among those we discuss in assessing treatment adherence. Although the deleterious effects of depression, malnutrition-inducing anorexia, or psychosis may outweigh bone-related risks of SSRIs or prolactin-increasing antipsychotic medications, you may wish to discuss bone health with your patients (particularly those at high risk) before prescribing these medications. During the maintenance phase of treatment, you may choose to include bone effects among the other risk and benefit factors that influence the decision to continue, adjust dosing, or eliminate medications in asymptomatic patients. For some vulnerable persons, initial treatment or a switch to maintenance with a nonserotonergic antidepressant may be a consideration.

It has not been and most likely will not become the psychiatrist’s role to treat bone disease, but these new data should increase the prominence of osteoporosis in our awareness. Loss of BMD occurs not only as a concomitant of aging but also as a con-sequence of medical or psychiatric disorders—and of the medications patients take and the ones we prescribe. As the clinical complexity of our patients and of our treatments continues to increase, psychiatrists can play a valuable role in patient care by heightening awareness of osteoporosis; increasing the recognition of at-risk individuals; and helping to prevent progression of this common, harmful, and potentially life-shortening condition.