Psychiatric Meds Boost Risk for Major Fractures

Pam Harrison

May 01, 2017

Psychotropic medications, including antidepressants, antipsychotics, and benzodiazepines, increase the risk for hip fractures and other major osteoporotic fractures, new research shows.

Furthermore, the FRAX tool, which predicts 10-year fracture risk in the general population, significantly underestimates fracture risk in patients taking psychiatric medications.

"We use these medications all the time — they are among the most commonly used medications in clinical practice," lead author James Bolton, MD, associate professor of psychiatry, psychology, and community health sciences, University of Manitoba, in Winnipeg, Canada, told Medscape Medical News.

"So physicians need to think about fracture risk as they are prescribing these medications, especially in patients who are vulnerable to fracture."

The study was published online April 19 in JAMA Psychiatry.

Medications Main Driver of Risk

Data were derived from the Manitoba Bone Density program database, which includes information on individuals who underwent a dual-energy x-ray absorptiometry (DEXA) scan from January 1, 1996, and March 28, 2013/

DEXA registry data were linked to administrative health data to determine which individuals had received a psychiatric diagnosis along with their medication history 1 year prior to undergoing the scan.

The cohort included of 62,275 women and 6455 men (mean age, 64.2 years). Mental disorders included depression, anxiety, and schizophrenia.

Major osteoporotic fractures included those of the hip, vertebrae, humerus, or forearm. The number of hip fractures or major osteoporotic fractures was documented in living residents between baseline bone mineral density assessment and the end of March 2013.

The overall rate of mental disorders was 18.9%. At a median observational interlude of 6.7 years, 8.4% of the cohort experienced a documented major osteoporotic fracture.

The rate of major osteoporotic fractures in those with a mental health disorder was 9.2% vs 8.2% in their mentally healthy counterparts (P > .001).

The rate of major osteoporotic fractures among those exposed to a psychotropic medication were also higher ― 9.8% vs 8.1%.

The same held true for the rate of hip fractures, which was 3% among those exposed to psychotropic medication vs 2.2% in unexposed participants (P < .001).

"When we did a more sophisticated analysis and took into account other factors at play, it's really the medications that seem to be the more important driver in terms of being a risk factor for fractures," said Dr Bolton.

Role of Mental Illness

The investigators also analyzed the association between fractures, psychiatric diagnosis, and the use of psychiatric medication, as adjusted for FRAX probability of fracture risk.

In this analysis, the investigators found that depression increased the risk for major osteoporotic fracture by 39%; anxiety disorders by 19%; and schizophrenia by 82%.

Further, all psychiatric medications, including selective serotonin reuptake inhibitors (SSRIs), antipsychotics, and benzodiazepines, were associated with an increased risk for both major osteoporotic fracture and hip fracture.

Table. Psychotropic Medications and Fracture Risk

  Major Osteoporotic Fracture Hip Fracture
SSRIs 47% 51%
Antipsychotics 48% More than twofold
Benzodiazepines 16% 23%


FRAX also significantly underestimated 10-year fracture risk across different psychiatric diagnoses. For example, FRAX underestimated the 10-year risk for major osteoporotic fracture by 29% for those with depression.

For patients who received an SSRI, FRAX underestimated major osteoporotic fracture risk by 36%; for patients who received a mood stabilizer or an antipsychotic, FRAX underestimated major osteoporotic fracture risk by approximately 60%.

FRAX was more predictive for those who had received a benzodiazepine; for such patients, the tool underestimated major osteoporotic fracture risk by only 13%.

The ability of FRAX to predict a patient's 10-year risk for hip fracture was similarly unreliable. For patients with depression, it underestimated hip fracture risk by 51%; for those who had received an SSRI, it underestiamted hip fracture by 57%; and for patients who had received a mood stabilizer, it underestimated the risk by 98%.

For individuals who had received an antipsychotic, the FRAX tool underestimated 10-year hip fracture risk by 171%, and for individuals who had been prescribed a benzodiazepine, it underestimated the risk by 31%.

In contrast, investigators found that the FRAX tool accurately estimated 10-year fracture risk for individuals who did not have a psychiatric disorder and for those who had not been prescribed psychotropic medications.

"Emerging evidence has shown that psychiatric medications are important risk factors for fracture, and when we tested this with the FRAX tool, we demonstrated that it underestimated fracture risk in these patients," said Dr Bolton.

"So it's an important issue, and physicians need to be aware that the FRAX tool is not going to fully capture fracture risk in these patients or the association between fracture risk and these psychiatric medications," he added.

No Surprise

Commenting on the study for Medscape Medical News, Douglas Kiel, MD, immediate past president of the American Society of Bone and Mineral Research, said the findings did not come as a surprise because other research, including his own, has shown that psychoactive drugs increase the risk for falls, and falls are usually what cause fractures.

"So it's not surprising that if you look at fractures, there's a link with these drugs," he said.

The fact that the FRAX tool underestimates fracture risk in patients taking psychiatric medications also makes sense, because the FRAX tool was derived from the general population, not subsets of the general population.

"In this study, FRAX was applied to a subset of women who were referred by their physician for a bone density scan, and you can bet your bottom dollar that the studies used to develop the FRAX tool did not resemble a clinically referred, mostly female population getting a bone density scan," said Dr Kiel.

The bottom line is that physicians really need to be aware that FRAX does not perform well in a population that does not resemble the population upon which the predictive tool was based and that psychotropic medications can be expected to increase the risk for falls and subsequent fractures, especially when first initiated or when the dose of the drug is increased.

"Clinically, physicians need to not blindly accept FRAX findings at face value, because certain things aren't in the FRAX, including falls and psychoactive medications," Dr Kiel advised.

"But if someone's life is miserable because they are suffering from severe depression, you just need to inform patients that you are going to prescribe a drug to help their mood, but you are concerned that the drug may affect them in such a way as it makes their chances of falling and fracturing a little more likely, so there is a need to be cautious with these drugs and advise people to be vigilant," he said.

No funding for the study has been disclosed. Dr Bolton has disclosed no relevant financial relationships. Two coauthors have disclosed relationships with pharmaceutical companies, as listed in the original article. Dr Kiel has disclosed no relevant financial relationships.

JAMA Psychiatry. Published online April 19, 2017. Abstract


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