SSRIs, Hypnotics Increase Fracture Risk

Medscape Medical News from: The American Society for Bone and Mineral Research (ASBMR) 2014

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September 22, 2014

HOUSTON, Texas — Use of hypnotic medications for insomnia and use of selective serotonin reuptake inhibitors (SSRIs) are each associated with an increased risk for osteoporotic and hip fractures in older women and men, independent of other risk factors on the fracture risk assessment tool FRAX, a new study shows.

While the FRAX assessment tool takes into account only use of oral glucocorticoids as a risk medication, the findings suggest the importance in also considering a patient’s use of medications in these other 2 drug classes, said first author Daniel Sundh, from the Center for Bone and Arthritis Research at the Sahlgrenska Academy, Institute of Medicine, University of Gothenburg, Sweden.

“Our results indicate that use of either of these medications increases fracture risk due to an increased susceptibility to falls,” he said. “Taking the risk these medications present into account could improve fracture prediction in older women and men.”

He presented the findings here at the American Society for Bone and Mineral Research (ASBMR) 2014 Annual Meeting.

Senior Alert

The study involved a large database of 128,596 older people enrolled in Sweden’s Senior Alert register, which includes details on patient age, sex, height, weight, and prevalent fall-related injuries at baseline.

The authors were able to determine incident fall-related injuries and osteoporotic and hip fractures, in addition to diseases that could cause secondary osteoporosis and mortality, by using cause-of-death and other data from the Swedish database.

The study’s follow-up, which included more than 80,000 patient-years, showed that 15,299 patients experienced fall-related injuries, 6730 had osteoporotic fractures, and 2557 had hip fractures. In addition, 40.9% of those with injuries had a history of a previous fall.

In the overall cohort, 17.4% of participants were using SSRIs and 19% were using hypnotic medications.

In terms of distribution of medications and specific outcomes, the authors found a significant association between the use of hypnotics and SSRIs and the prevalence of fall-related injuries (50.7% for SSRI use vs 38.8% for no SSRI use; 45% for hypnotic use vs 40% for no hypnotic use; P < .001 for both).

The rates for similar for osteoporotic fracture (22.4% for SSRI use and 15.2% for no SSRI use; 19.5% for hypnotic use and 15.7% for no hypnotic use; both P < .001).

The incidence of hip fracture, meanwhile, was 2.3% among those using SSRIs vs 1.9% for those not using the drugs and 2.2% for those using hypnotics vs 1.9% for no hypnotic use (P < .001).

In further adjusting for risk factors in the FRAX assessment tool, including age, sex, height and weight, secondary osteoporosis, prevalent osteoporotic fracture, glucocorticoid use and rheumatoid arthritis, the researchers found the increased risk for hip fracture to be 30% among those using SSRIs and 21% for those using hypnotics.

The associations for osteoporotic fracture were weaker but still significant, Sundh said.

The study’s limitations include the following: Adjustments for all FRAX variables were not possible in the large cohort, and there were no adjustments for the underlying diagnosis that the medications were being used for, including depression and insomnia.

Strengths, however, include the study’s exceptionally large sample size and the long follow-up time, Sundh said.

“We found that both SSRIs and hypnotics are associated with increased risk of fall-related injury, osteoporotic and hip fracture, and the increased fracture risk associated with the use of SSRIs or hypnotics is independent of many risk factors in FRAX.”

Evidence of links between both drug classes and fractures has mounted in recent years, including 1 study, reported by Medscape Medical News, showing nursing home residents using nonbenzodiazepine sleep agents to have as much as a 66% increased risk for hip fracture.

The hypnotic sleep agent drugs, which include agents such as zolpidem, eszopiclone, and zaleplon, are typically considered to be safer than benzodiazepine drugs because they are less addictive, but the mounting evidence suggests otherwise.

Large Database

Previous research has shown a link with SSRIs, and the study is notable for its extremely large database. However, a big remaining question is the specific cause of the fractures, Piet Guersens, MD, of the University Maastricht, the Netherlands, and University Hasselt, Belgium, told Medscape Medical News.

“The study showed more fractures and more falls, but what it didn’t show is that less fractures occurred because of less falls,” he told Medscape Medical News.

“[The authors] deduced hypothetically the fractures occurred because of the falls but they didn’t prove that.”

“A big question is whether there is an effect of the medications on the bone or on falls and balance. So there is a need for more studies to determine if is only bone, or it is only falls, or both. My impression is that it could be both,” he said.

“The study is important however, particularly due to its size — the very large database is far greater than cohorts that were used in previous studies on this issue.”

The study received funding from the Swedish Research Council. Daniel Sundh and Dr. Guersens have disclosed relevant financial relationships.

American Society for Bone and Mineral Research (ASBMR) 2014 Annual Meeting. Abstract 1015. Presented September 14, 2014.