Selective serotonin reuptake inhibitors (SSRIs) account for approximately 62% of all antidepressants prescribed in the United States. There have been several recent studies suggesting that SSRIs may lower bone mineral density in individuals over the age of 65. However, depression itself has been shown to decrease bone mineral density and has also been associated with an increased risk of hip fractures in older women.

Diem and colleagues found that the rate of bone density loss was 1.6-fold higher among SSRI users than among non-users of antidepressants. Haney and colleagues found that the bone mineral density was 3.9% lower among elderly men who took SSRIs compared with TCAs or no antidepressants. In addition, the risk for hip fracture was greater in those taking SSRIs compared to those on tricyclic antidepressants (TCAs).

The exact mechanism for bone loss among SSRI users is unclear. There are serotonin transporters in osteoblasts, osteoclasts, and osteocytes. Animal studies have indicated that mice with disruption in serotonin transporter genes have lower bone mineral density. Fluoxetine has been shown to decrease osteoblast formation and osteoclast differentiation in vitro. However, the evidence in humans is limited.

The authors of these studies warn that it may not be appropriate to generalize these findings to younger populations; the mean age of the women in Diem’s study was 78. It is also difficult to determine the impact of depression on bone mineral density; while these studies indicated that bone mineral density was lower in individuals taking SSRIs versus non-SSRI antidepressants, the authors point out that many non-SSRI antidepressants, such as trazodone and TCAs, are not prescribed for depression but may be used to treat other problems such as sleep or pain syndromes and are typically used at lower doses.

Although further investigation is necessary to better define the impact of SSRI use on bone mineral density, it may be helpful for elderly patients with other risk factors for osteoporosis to speak with their health care providers about screening for bone loss and to consider preventive interventions that minimize this risk.

Kimberly Pearson, MD

References:

Diem SJ, Blackwell TL, Stone KL, Yaffe K, Haney EM, Bliziotes MM, Ensrud KE. Use of antidepressants and rates of hip bone loss in older women. Arh Intern Med. 2007:167:1240-1245.

Haney EM, Chan BK, Diem SJ, Ensrud KE, Cauley JA, Barrett-Connor E, Orwoll E, Bliziotes MM; for the Osteoporotic Fractures in Men Study Group. Association of low bone mineral density with selective serotonin reuptake inhibitor use by older men. Arch Intern Med. 2007: 167:1246-1251.

Hubbard R, Farrington P, Smith C, Smeeth L, Tattersfield A. Exposure to tricyclic and selective serotonin reuptake inhibitor antidepressants and the risk of hip fractures. Am J Eipdemiol 2003:158:77-84.

Liu B, Anderson G, Mittmann N, To T, Axcell T, Shear N. Use of selective serotonin reuptake inhibitors or tricyclic antidepressants and risk of hip fractures in elderly people. Lancet. 1998:351:1303-1307.