Nonbenzodiazepine Hypnotic Drugs and Fracture Risk

Since 2006, Medicare Part D has had a policy that excludes benzodiazepines from mandatory drug coverage. The restriction had increased the use of nonbenzodiazepine sleep medications (zolpidem tartrate) to treat insomnia in nursing homes in the United States.

Nonbenzodiazepines were initially thought to be safer than benzodiazepines in respect to risk of falls, however, a case-control study found the use of nonbenzodiazepine hypnotic drugs was associated with a 2-fold increase in the risk of hip fracture. In addition, initiation of a nonbenzodiazepine hypnotic drug is associated with a 1.7 to 2.2 times greater risk for fracture compared with short-acting benzodiazepine use.

Noting that the suggested harm demonstrated in these studies may be due to intrinsic differences between nursing home residents prescribed a sleep medication and those not prescribed a sleep medication, researchers recently conducted a case-crossover study. The primary objective of the study was to estimate the association between nonbenzodiazepine hypnotic drug use (zolpidem tartrate, eszopiclone, or zaleplon) and the risk for hip fracture. Study results were reported in JAMA Internal Medicine [2013;173(9):754-761].

The researchers linked Medicare Part A and Part D claims to nursing home resident assessments using unique, individual identifiers. After applying inclusion and exclusion criteria, the study participants were 15,528 long-stay nursing home residents ≥50 years of age with a hip fracture documented between July 1, 2007, and December 31, 2008.

The primary outcome measures were odds ratios (ORs) of hip fracture. ORs were estimated by comparing the exposure to nonbenzodiazepine hypnotic drugs during the 0 to 29 days prior to the hip fracture (hazard period) with the exposure during the 60 to 89 and 120 to 149 days before the hip fracture (control period).

Of the 15,528 participants, 11.0% (n=1715) had been dispensed a nonbenzodiazepine hypnotic drug. Of the study participants who used a nonbenzodiazepine hypnotic drug during the hazard or control period (but not in both periods), 77.6% were female and mean age was 81.0 years.

The risk factor for hip fracture was higher among those who used a nonbenzodiazepine hypnotic drug (OR, 1.66; 95% confidence interval [CI], 1.45-1.90). In new users, the association between nonbenzodiazepine hypnotic drug use and fracture risk was somewhat greater (OR, 2.20; 95% CI, 1.76-2.74), and the risk seemed to be greater during the first 15 days of use of the medication.

The association was also greater in residents with mild versus moderate to severe cognitive impairment (OR, 1.86 vs 1.43; P=.06), moderate versus total or severe functional impairment (OR, 1.71 vs 1.16; P=.11), limited versus full assistance required with transfers (OR, 2.02 vs 1.43; P=.02), or in a facility with fewer Medicare beds (OR, 1.90 vs 1.46; P=.05).

Limitations cited by the researchers included (1) not considering the dosage of nonbenzodiazepine hypnotic drug used, (2) the possibility that interaction with traditional benzodiazepines further increased the risk of fracture, (3) exclusion of the 34% of nursing home residents who met other eligibility requirements because they were not enrolled in Medicare Part D, and (4) an inability to completely separate the effects of the hypnotic drug use from the associated medical condition or a worsening of the medical condition with respect to the risk for hip fracture.

In summary, the researchers commented, “The risk for hip fracture is elevated among nursing home residents using a nonbenzodiazepine hypnotic drug. New users and residents having mild to moderate cognitive impairment or requiring limited assistance with transfers may be most vulnerable to the use of these drugs. Caution should be exercised when prescribing sleep medications to nursing home residents."