Study Links Sleeping Pills to Hip Fractures in the Elderly

Every year, more than 300,000 older Americans are hospitalized due to hip fractures (breaks in the upper part of the thighbone), and almost all of these fractures are caused by falls.[1] Hip fractures in the elderly increase the risk of death within three months by fivefold to eightfold[2] and lead to significant limitations in daily activities among survivors.

A number of observational studies have found a relationship between two drug classes — benzodiazepines and a similarly acting class of sleep medicines often called “Z-drugs” — and the risk of fractures, including hip fractures.[3],[4],[5],[6],[7] These medications, however, continue to be widely used, particularly by the elderly: A 2008 study showed that 9 percent of Americans aged 65 to 80 who live in a community used a benzodiazepine, and nearly one-third of these users took these medications on a long-term basis.[8]

A recent analysis of data from multiple similar studies that was performed by British researchers with government and foundation funding concluded that there is “strong evidence” that benzodiazepines and Zdrugs are associated with an increased risk of hip fractures in the elderly. This analysis was published in PLOS ONE in April 2017.[9]

About benzodiazepines and Z-drugs

Benzodiazepines are sedative hypnotics used to induce or maintain sleep and to treat acute anxiety. These drugs include alprazolam (XANAX), chlordiazepoxide (LIBRAX, LIBRIUM), diazepam (DIASTAT, DIASTAT ACUDIAL, DIAZEPAM INTENSOL, VALIUM), lorazepam (ATIVAN, LORAZEPAM INTENSOL), oxazepam (generic only) and temazepam (RESTORIL).

The Z-drugs — zaleplon (SONATA), zolpidem (AMBIEN, EDLUAR, INTERMEZZO, ZOLPIMIST) and eszopiclone (LUNESTA) — are hypnotics with similar effects to benzodiazepines. They are approved for short-term relief of insomnia, although they have shorter duration of action relative to benzodiazepines.

Public Citizen’s Health Research Group classifies all benzodiazepines (except for alprazolam, which can be used for treating panic disorder) and Z-drugs as Do Not Use for people of any age. These drugs are controlled substances that carry many risks (including dependence, addiction and serious impairment of multiple cognitive and physical functions) that greatly outweigh their limited effectiveness.

The PLOS ONE analysis

The British researchers analyzed data from 18 clinically similar observational studies published from 1995 through May 2015 that examined the relationship between the use of benzodiazepines or Z-drugs and the risk of hip fractures.[10] All of these studies included only patients who were aged 50 or older; the patients had an average age over 65.

They compared patients who were prescribed either benzodiazepines or Z-drugs with similar patients who were not taking these medications. No randomized clinical trials were included because the researchers did not identify such studies when they reviewed the literature.

The researchers found a strong, statistically significant association between the use of either of these drugs in the elderly and the risk of hip fractures. Overall, benzodiazepines increased the risk of hip fractures by 52 percent and Z-drugs increased it by 90 percent in elderly users compared with elderly nonusers.

The increased risk of hip fractures was consistent over time, but it was highest among short-term (less than 15 days) users. Specifically, short-term users of benzodiazepines and Z-drugs had a 140 percent and 139 percent increased risk of hip fractures, respectively, compared with nonusers.

The researchers noted that their findings raise a debate about the riskbenefit ratio of these medications and the need to explore the relative effectiveness of the non-drug approaches to treat the conditions for which these medications are taken — mainly insomnia.

Conclusions

The new evidence from the PLOS ONE study coupled with the earlier evidence about the increased risk of memory disorders, daytime drowsiness, traffic accidents and withdrawal reactions associated with use of benzodiazepines and Z-drugs[11],[12] lends further support to our recommendation against using these medications.

Additionally, the American Geriatrics Society has recently recommended avoiding short- and mediumacting benzodiazepines and Z-drugs for treating insomnia for any period because their harms outweigh their minimal benefits.[13]

What You Can Do

Do not take benzodiazepines (except alprazolam for panic disorder that is unresponsive to other treatments) or Z-drugs, especially if you are a senior citizen or at risk of falling. If you are currently taking any of these drugs, do not stop your medication suddenly without consulting your doctor because doing so can cause withdrawal reactions.

If you have insomnia, try non-drug sleep-hygiene practices, such as going to bed at the same time every night, exercising (but not within the few hours before bedtime), and avoiding caffeine, nicotine and alcohol, especially later in the day.[14] All senior citizens, whether using these drugs or not, should ask their doctors to evaluate their risk of falling and should inquire about the specific actions that they can take to minimize falling and subsequent fractures or injuries. Such actions include correcting eyesight problems, increasing lighting throughout the house (especially at the top and bottom of stairs) and installing grab bars in the tub or shower and near the toilet.[15]

References

[1] Centers for Disease Control and Prevention. Hip fracture among older adults. Last updated September 20, 2016. https://www.cdc.gov/homeandrecreationalsafety/falls/adulthipfx.html. Accessed November 7, 2017.

[2] Haentjens P, Magaziner J, Colón-Emeric CS, et al. Meta-analysis: excess mortality after hip fracture among older women and men. Ann Intern Med. 2010;152(6):380-390.

[3] Xing D, Ma XL, Ma JX, et al. Association between use of benzodiazepines and risk of fractures: a meta-analysis. Osteoporos Int. 2014;25(1):105-120.

[4] Berry S, Lee Y, Cai S, et al. Nonbenzodiazepine sleep medication use and hip fractures in nursing home residents. JAMA Intern Med. 2013;173(9):754-761.

[5] Golden AG, Ma Q, Nair V, Al E. Risk for fractures with centrally acting muscle relaxants: an analysis of a national Medicare Advantage claims database. Ann Pharmacother. 2010;44(9):1369-1375.

[6] Coutinho ES, Fletcher A, Bloch KV, et al. Risk factors for falls with severe fracture in elderly people living in a middle-income country: a case control study. BMC Geriatr. 2008;8(21). doi:10.1186/1471-2318-8-21.

[7] Chang C, Wu E, Chang I, Lin K. Benzodiazepine and risk of hip fractures in older people: A nested case-control study in Taiwan. Am J Geriatr Psychiatry. 2008;16(8):686-692.

[8] Olfson M, King M, Schoenbaum M. Benzodiazepine use in the United States. JAMA Psychiatry. 2015;72(2):136-142.

[9] Donnelly K, Bracchi R, Hewitt J, et al. Benzodiazepines, Z-drugs and the risk of hip fracture: a systematic review and meta-analysis. PLoS One. 2017;12(4):e0174730.

[10] Ibid.

[11] Sleep complaints: Whenever possible, avoid the use of sleeping pills. Prescrire Int. 2008;17(79):206-212.

[12] Gunja N. In the Zzz Zone: The effects of Z-drugs on human performance and driving. J Med Toxicol. 2013;9(2):163-171.

[13] The American Geriatrics Society 2015 Beers Criteria Update Expert Panel. American Geriatrics Society 2015 updated beers criteria for potentially inappropriate medication use in older adults. J Am Geriatr Soc. 2015;63(11):2227-2246.

[14] All sleeping pills are still risky, but safer alternatives exist. Worst Pills, Best Pills News. December 2013. /newsletters/view/877. Accessed November 7, 2017.

[15] National Council on Aging. 6 steps for preventing falls among your older loved ones. https://www.ncoa.org/healthy-aging/falls-prevention/preventing-falls-tips-for-older-adults-and-caregivers/6-steps-to-protect-your-older-loved-one-from-a-fall/. Accessed November 7, 2017.