Zoledronic Acid Improved Bone Density in Frail Elderly Women

A single IV dose of zoledronic acid improved bone mineral density in frail elderly women living in nursing homes and long-term care facilities.

In a group of frail elderly women residing in nursing homes and long-term care facilities, one intravenous (IV) dose of zoledronic acid improved bone mineral density (BMD) over 2 years, according to new data published in JAMA Internal Medicine.

“Nearly 2 million frail elderly Americans reside in long-term care facilities, and another 4 to 6 million similarly frail elderly people live in the community,” study researcher Susan L. Greenspan, MD, of the University of Pittsburgh, and colleagues wrote. “Eighty-five percent of such individuals have osteoporosis and their bone fracture rates are 8 to 9 times higher than those observed among less impaired elderly persons.”

Furthermore, the consequences of a hip fracture in this patient population can be dire, leading to decreased mobility and independence as well as potential death. Even so, many of these patients do not receive osteoporosis treatment and are often excluded from osteoporosis trials, the researchers noted.

For this study, Greenspan and colleagues opted to study the safety and efficacy of zoledronic acid to treat osteoporosis in frail elderly women living in long-term care facilities. They selected zoledronic acid because it can be administered in one dose and has effects that may last out to 2 years.

The researchers randomly assigned 181 women aged at least 65 years with osteoporosis living in nursing homes and assisted-living facilities to receive a single 5-mg IV dose of zoledronic acid (n=89) or placebo (n=92), along with daily vitamin D and calcium supplementation. Participants with cognitive impairment, immobility and multiple coexisting illnesses were included in the study.

Hip and spine BMD as well as adverse events were evaluated at 12 and 24 months.

The researchers observed no differences in age (mean, 85.4 years), BMD, or functional or cognitive status at baseline, although the zoledronic acid group included more participants with frailty, falls history, diabetes and anticonvulsant medication use.

Results revealed greater increases in average total hip BMD in the zoledronic acid group vs. the placebo group at 12 (2.8% vs. –0.5%) and 24 months (2.6% vs. –1.5%). Similarly, average spine BMD increased more in the treatment group vs. the placebo group at 12 (3% vs. 1.1%) and 24 months (4.5% vs. 0.7%).

Fracture rates were 20% and 16% for the treatment and placebo groups, respectively, with an OR of 1.30 (95% CI, 0.61-2.78). Mortality rates were 16% and 13%, respectively, with an OR of 1.24 (95% CI, 0.54-2.86).

Although the proportion of single fallers did not differ significantly between groups, more participants in the zoledronic acid group experienced multiple falls (49% vs. 35%; OR=1.83; 95% CI, 1.01-3.33). The difference lost significance, however, after adjustment for baseline frailty.

“In summary, we found that a single infusion of zoledronic acid in frail, cognitively challenged, less mobile elderly women improved bone density and reduced bone turnover for two years. This suggests that even a very frail cohort may benefit,” the researchers wrote.

“However, prior to changing practice, larger trials are needed to determine whether improvements in these surrogate measures will translate into fracture reduction for vulnerable elderly persons.”

In an invited commentary, Robert Lindsay, MB, ChB, PhD, of Helen Hayes Hospital in West Haverstraw, New York, discussed the implications of these findings, noting that that the study is limited by its relatively small size — hundreds of participants vs. thousands — and the fact that it was not designed as a fracture study.

“It would be premature to use this study to immediately modify our clinical use of potent bone-active agents in the nursing home population with documented osteoporosis (i.e. those who have a low BMD as a major risk factor for fracture,” Lindsay wrote.

Nevertheless, the study poses important questions, according to Lindsay.

“Finally, this study draws attention to the need for large controlled clinical trials to determine if a combination of fall prevention strategies and treatment with bone-active drugs might produce additive benefits on fractures, especially in high-risk populations such as those living in nursing homes. These studies will be difficult, and Greenspan and her colleagues are to be congratulated on beginning to fill this void,” Lindsay concluded.


  1. Greenspan SL et al. JAMA Intern Med. 2015;doi:10.1001/jamainternmed.2015.0747.
  2. Lindsay R. JAMA Intern Med. 2015;doi:10.1001/jamainternmed.2015.0757.