Schizophrenia Associated With Bone Fragility and Fracture Risk

A comprehensive review and meta-analysis published in Translational Psychiatry has affirmed that individuals with schizophrenia have more fragile bones than those without the disorder, which carries an increased risk of fractures.

“Our findings regarding poor bone health in people with schizophrenia are concerning, given previous studies have indicated that this population experiences more adverse events following a fracture event, including longer length of hospitalization, higher risk of adverse perioperative events and acute post-operative complications, and in turn increased healthcare costs,” wrote Behnaz Azimi Manavi, Ph.D., of Deakin University in Geelong, Australia, and colleagues. “[I]t is not unrealistic to suggest that poorer outcomes associated with bone fragility contribute to the higher mortality rate in this population.”

Manavi and colleagues examined data from 29 studies that compared markers of osteoporosis in adults with schizophrenia with those of adults without the disorder; this included studies assessing bone mineral density, bone quality (strength and stiffness), bone turnover (the rate new bone is laid down and old bone removed), and/or risk of fracture. The studies encompassed 52,246 adults with schizophrenia along with over 4 million control individuals.

In total, the study data indicated that adults with schizophrenia have lower bone density (particularly at the hip), poorer bone quality, and higher rates of bone turnover; no significant differences between males and females were identified. A meta-analysis of seven studies that included fracture data found that adults with schizophrenia have a 32% increased risk of fracture, after adjusting for potential biases, again with no risk difference between males and females.

Manavi and colleagues noted that since schizophrenia is associated with premature mortality and the risks of osteoporosis increase with age, their findings may underestimate the true burden of schizophrenia on bone health in older adults.

“Further research is needed to evaluate the etiology of bone fragility in this population and recognize modifiable risk factors such as lifestyle or medications to reduce the potential risk for this patient group. Importantly, there is a need to develop guidelines for preventing risk factors and predicting fracture in people with schizophrenia,” they concluded.

For related information, see the Psychiatric News article “Study Calculates Disability Caused by Schizophrenia.”

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Seniors With Depression May Be at Heightened Risk of Hip Fracture Before Starting Antidepressants

Despite several observational studies demonstrating that older patients taking antidepressants are at a higher risk of falls and fractures, it has remained unclear whether the use of the medication causes the increased risk. A study published today in JAMA Psychiatry suggests that older adults may be at higher risk of hip fracture even before they start taking antidepressants.

While the findings raise questions about the association between antidepressant drug use and hip fracture, study authors Jon Brännström, M.D., of Umeå University in Sweden and colleagues cautioned that doctors should continue to limit the prescription of antidepressants to older adults.

For the study, Brännström and colleagues focused on adults aged 65 years or older in Sweden who had filled a prescription for antidepressants between July 1, 2006, and December 31, 2011. The authors compared hip fracture data from one year before to one year after the date that the participant first filled the prescription for an antidepressant. Each participant was matched with one control (an adult of the same sex and age who did not use antidepressants during the study period). In total, 408,144 adults (mean age, 80.1 years) were included in the analysis.

The authors found that participants in the antidepressant group had more than twice as many incidents of hip fracture before and after the initiation of treatment than did those who did not take antidepressants. The odds ratio (OR) for the association between any antidepressant use and hip fracture peaked 16 to 30 days before the prescription was filled (OR, 5.76)—a pattern that was consistent in all separate analyses of age groups, of men and women, and of the three most commonly prescribed antidepressants (citalopram hydrobromide, mirtazapine, and amitriptyline hydrochloride), the authors noted.

“Based on our results, we suggest that older people with depression have an increased risk of hip fracture before starting antidepressant treatment, owing to a high burden of comorbidity and confounding by indication,” Brännström and colleagues wrote. “Even if antidepressant drug use does not increase the risk of hip fracture, the prescription of antidepressants to older people should be restrictive, as the evidence for positive effects is limited.”

In an accompanying editorial, Andrea Iaboni, M.D., D.Phil., of the University of Toronto and Donovan T. Maust, M.D., M.S., of the University of Michigan recommended that doctors continue to communicate the potential risks of antidepressants for older patients: “We suggest that clinicians would still be wise to inform patients about the potential risk of falling and fractures that may follow antidepressant use to allow patients to make an informed decision about treatment,” they wrote. “[F]or most older adults, the toll of untreated depression will likely outweigh the potential risks associated with antidepressant use, including falls or fractures.”

Iaboni and Maust also recommended that doctors avoid prescribing sedating or anticholinergic agents, start patients on a low dose that can be increased over time, and review other medications that patients may be taking that could increase risk of falls and fractures.

For related information, see the Psychiatric News article “Patients Taking Psychotropic Medications Found to Be at Elevated Risk of Fractures.”

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Antidepressants May Increase Risk of Hip Fractures in Older Adults

Older adults taking antidepressants—particularly those with Alzheimer’s disease (AD)—appear to be at a greater risk of hip fracture than older adults not taking the medications, according to a report in the International Journal of Geriatric Psychiatry.

“Antidepressant use is associated with an increased risk of incident hip fracture among older persons with and without AD,” the study authors wrote. “Thus, if the antidepressant treatment is necessary, other risk factors for falling should be carefully considered.”

For the study, researchers from the University of Eastern Finland compared the health outcomes of 50,491 community-dwelling adults who were diagnosed with AD (mean age 80) and 100,982 age- and sex-matched controls without an AD diagnosis documented in national registers over a four-year period.

A total of 22.4% of the people with AD and 9.9% of persons without AD started taking antidepressants during the study period. (The most frequently initiated antidepressants included selective serotonin reuptake inhibitors, mirtazapine, and selective noradrenaline reuptake inhibitors.) 

During antidepressant use, the age-adjusted rate of hip fractures per 100 person-years was 3.01 among persons with AD and 2.28 among persons without AD. Antidepressant use was associated with an increased risk of hip fracture among persons with and without AD (adjusted hazard ratio [HR]=1.61; HR=2.71, respectively) compared with nonuse. This increased risk remained even after adjusting for use of antipsychotics, benzodiazepines, and other psychotropic drugs during the follow-up period.

“In our study, the adjusted hazard ratio was higher among persons without AD than in persons with AD. However, we found age-adjusted event rate for hip fracture per 100 person-years during antidepressant use was higher among persons with AD compared with persons without AD, which indicates the vulnerability of persons with AD.”

Additional analysis revealed that the risk of hip fracture was highest at the beginning of antidepressant use (1 to 30 days) in people with AD and without AD (HR=3.30; HR=3.92, respectively), but remained throughout the follow-up.

For related information, see the Psychiatric Services article “Antidepressant Prescribing in Primary Care to Older Adults Without Major Depression.” 

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