Depression, SSRIs May Affect Bone Mass in Teens and Young Adults
By Joan Stephenson
NEW YORK—Major depressive disorder (MDD) and use of selective serotonin reuptake inhibitors (SSRIs) are associated with changes in bone metabolism in older adolescents and young adults, but the relationship is “complex,” with different effects in men and women, according to new research.
“Depression was associated with increased bone mass in the lumbar spine, and use of SSRIs was associated with an increase in bone mass in the lumbar spine in females but a decrease in males,” Dr. Chadi A. Calarge, of Baylor College of Medicine in Houston, told Reuters Health by email.
The findings of the prospective observational cohort study were surprising, he said, “because everything we found (except for the effect of SSRIs in males) was contrary to our hypothesis” that, after accounting for depression severity, SSRI use would be associated with reduced bone-mineral content.
Bone mass increases dramatically during adolescence, and the amount of bone banked by the end of that period is a major determinant of future risk of osteoporosis and fractures. Depression and SSRIs have been associated with low bone mass among adults in previous studies.
To investigate whether MDD and SSRI use have independent, detrimental effects on bone health in adolescents, the researchers recruited 264 medically healthy 15- to 20-year-olds (88% white) from 2010 to 2014 and followed them for a median of 1.5 years. Participants either were not taking an SSRI or were within a month after starting one.
The researchers also examined the association between generalized anxiety disorder (GAD) and bone mineralization because MDD and GAD frequently coexist.
Surprisingly, depression burden (reflected in the number of weeks meeting criteria for a major depression episode) “was associated with increased bone mass at the lumbar spine over time, both in male and female participants,” after adjustment for age, sex, plasma vitamin D levels, physical activity, lean mass, and other factors, the researchers report in the Journal of Bone and Mineral Research, online September 22.
SSRI use was associated with significantly increasing lumbar spine areal bone mineral density (aBMD) Z-score over time among female participants - and with significantly decreasing lumbar spine aBMD Z-score among males. After accounting for depression, GAD also was significantly (but weakly) associated with increased bone mineralization.
Dr. Calarge noted that several mechanisms are proposed to account for a connection between depression and bone loss, but he and his colleagues have no explanation for the observed increase in bone mass over time in their study.
“If others replicate these findings, we would have more support to dismiss the idea that depression causes bone loss, which is important from a public health perspective, given the high prevalence of depression,” he said. “It may also simply be a correlate, reflecting other factors that might affect bone.”
The study assesses an age group that has not been well studied with respect to SSRIs’ skeletal effects, but the findings raise hypotheses rather than provide clear-cut answers, Dr. Rene Rizzoli, of Geneva University Hospitals and Faculty of Medicine, in Switzerland, told Reuters Health by email.
The study leaves several questions unanswered, said Dr. Rizzoli, an expert on metabolic bone diseases and disorders of mineral metabolism, who was not involved in the current study. For example, information on the menstrual status of females and whether it was altered among those taking SSRIs is lacking.
In addition, if muscle wasting occurred during follow-up, the adjustment for lean mass may lead to overestimation of changes in bone. If muscle wasting occurred mainly in females, that might explain the apparent gain in bone in females and not in males, he said.
The study “provides some reassurance that clinical use of SSRIs in this population may not lead to a decrement in bone mass, as suggested by the adult literature,” Dr. Alexis Feuer, a pediatric endocrinologist from Weill Cornell Medicine in New York City, said in an email.
This, and the unexpected finding that SSRI use was associated with a decrease in bone-mass accrual in male participants but an increase in females, “merit further evaluation to elucidate potential mechanisms and to better characterize sexually dimorphic risk factors,” said Dr. Feuer, who was not involved in the study.
She observed that although the study excluded use of other psychotropic medications, the allowed use of stimulant medications might have been a confounding factor. “Stimulant medications increase beta-2 adrenergic signaling and have been shown to be associated with lower bone mass in adolescents and young adults in observational studies.”
“Epidemiologic data show stimulant use is far more prevalent in males than females, so it is possible that some of the discrepancy between the males and females may be due to stimulant use that was not controlled for in the data analysis,” she said.
J Bone Miner Res 2017.
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