Marlene Busko

October 13, 2015

SEATTLE — The World Health Organization's Fracture Risk Assessment Tool (FRAX) underestimates the 10-year fracture risk for people with mental illness—notably depression—and those taking drugs for psychiatric conditions—notably selective serotonin reuptake inhibitors (SSRIs), mood stabilizers (lithium, anticonvulsants, atypical antipsychotics), other antipsychotics, or benzodiazepines, claims new research.

The lead author says this does not mean that this fracture-risk-stratification tool needs to be revamped but that physicians and patients need to be more aware of the heightened risk of having a fracture when taking certain medications for mental illness.

"I'm not calling for 'Psycho-FRAX,' " said Dr William Leslie, from the University of Manitoba, in Winnipeg, presenting his findings here at the American Society for Bone and Mineral Research (ASBMR) 2015 Annual Meeting.

However, "clearly we have to increase awareness of the high prevalence of mental-health disorders and the fact that these medications and the diagnoses are at least markers for fracture risk," he stated.

Moreover, many individuals with psychiatric illnesses (which in this study consisted of depression, anxiety, and schizophrenia) are less likely to receive care to prevent fractures, Dr Leslie noted.

Psychiatric Diagnosis, Meds, and Fracture Risk

FRAX integrates clinical risk factors (age, sex, weight, height, previous fracture, a parent who had a hip fracture, current smoking, glucocorticoids, rheumatoid arthritis, having a related disorder, and drinking alcohol) and bone-mineral density at the femoral neck to calculate a person's 10-year probability for having a major osteoporotic fracture (of the spine, forearm, hip, or shoulder) and/or a hip fracture.

"FRAX was developed from population-based cohorts, and, not surprisingly, it performs well in risk stratification for the general population, but there's been increasing work to see the applicability of that tool in specific subgroups," including patients who are obese or who have type 2 diabetes, explained Dr Leslie.

However, a few studies have also suggested that "psychiatric illnesses and the many medications that are used to treat these…are associated with an increased fracture risk, possibly through effects on bone metabolism," he added.

Mental illness is common, and in 2013, about one in five adult men and women in the United States and Canada had a mental illness, and the same proportions were taking a psychoactive medication, Dr Leslie continued. Among women aged 25 to 79 years, 14% were taking an antidepressant, for example.

To investigate the effect of psychiatric illness and medications on FRAX score, the researchers analyzed data from 68,739 men and women who were part of the Manitoba Bone Density Program cohort and were 40 or older in 1996–2013 when they had bone-mineral density measured by dual-energy X-ray absorptiometry (DEXA).

The participants had a mean age of 64. Most (90%) were women and most were also osteopenic.

About 20% had a diagnosed mental illness: 6824 patients (9.6%) had depression, 6425 patients (9.0%) had anxiety, and 203 patients (0.3%) had schizophrenia.

Close to a third of the patients (n = 21,915, 30.7%) used psychiatric medications, specifically SSRIs, tricyclic antidepressants, other antidepressants, lithium, other mood stabilizers, antipsychotics, and benzodiazepine.

And close to half of these (n = 12,263, 17.2%) had used these drugs more than half of the time in the previous 12 months (and so were defined as the high-exposure group).

Need to Examine the Role of Falls in Findings

During a median follow-up of 7 years, 5750 patients (8.1%) had a first major osteoporotic fracture, 1579 patients (2.2%) had an incident hip fracture, and 8998 participants (12.6%) died.

High exposure to SSRIs, antipsychotics, and benzodiazepines were each associated with an increased risk for having a major osteoporotic fracture and having a hip fracture.

FRAX scores underestimated the 10-year risk of either type of fracture for patients with depression or high exposure to SSRIs, nonlithium mood stabilizers, antipsychotics, or benzodiazepines.

Dr Leslie conceded that the fact that these were registry data, lacking information about patients' lifestyle or about falls, was a study limitation. But on the other hand, this was a large cohort of patients who are typical of those seen in clinical practice, and by analyzing claims data the researchers were able to eliminate recall bias.

Thus, the study suggests that "some psychiatric illnesses and medications that are used to treat these [conditions] are associated with increased fracture risk independent of FRAX score," he summarized.

"Falls may be a mediating factor," he added. "There's an important opportunity for research."

In reply to a question from the audience, he clarified that fractures that were related to trauma or violence were not included in this study. They also adjusted for socioeconomic factors, and the findings were unchanged.

"Did you adjust for duration of therapy?" a member of the audience asked. "Not yet," Dr Leslie conceded. They also did not yet examine the time between the prescription for a psychiatric drug and the fracture, he said.

Dr Leslie had no relevant financial relationships.

American Society for Bone and Mineral Research 2015 Annual Meeting; Seattle, Washington. Abstract 1065, presented October 10, 2015.


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