Efficacy and Safety of Single-Dose Zoledronic Acid for Osteoporosis in Frail Elderly Women: A Randomized Clinical Trial

Hoa Tang, Mercer University College of Pharmacy 2015

According to the National Institute of Arthritis and Musculoskeletal and Skin Diseases, osteoporosis, which is a silent disease characterized by low bone mass, places patients at risk for bone fractures and falls.  It is suggested that osteoporosis is preventable and treatable. The suggested goal of osteoporosis treatment is facture prevention.  Bisphosphonates are recommended for treatment of osteoporosis.1 It was reported that the prevalence of osteoporosis in geriatric patients was high, but treatment rate of elderly patients with osteoporosis was low in practice. The suggested reasons for under-treatment of osteoporosis may be due to polypharmacy, risk of drug interactions, and medication noncompliance.2

A recently published study assessed the efficacy and safety of single-dose zoledronic acid for osteoporosis in frail elderly women.3

Title: Efficacy and Safety of Single-Dose Zoledronic   Acid for Osteoporosis in Frail Elderly Women: A Randomized Clinical Trial
Design Randomized, double-blinded, placebo-controlled study; N= 181
Objective To determine the impact of a single-dose zoledronic acid on bone mineral density (BMD) and safety for two years in frail women residents in long-term care (LTC) facilities
Study Groups Zoledronic acid group (n= 89) versus placebo group (n= 92)
Methods Participants were randomized to infusion with either 5 mg of IV zoledronic acid or placebo. All participants received daily calcium and vitamin D supplements.
Duration December 2007 through March 2012
Primary Outcome Measure Percentage change in BMD of the total hip and spine at 12 months
Baseline Characteristics

 

Frail women 65 years or older with a history of vertebral or hip fractures or a measured BMD below the treatment cutoff for osteoporosis

Zoledronic acid group- mean age 85.4 years, BMI 28.2, anticonvulsant medication use 10%, Fried Frailty Index 72%, diabetes 28%, fall once in the previous year 50%, recurrent falls in the previous year 26%

Placebo group- mean age 85.5 years, BMI 26.9, anticonvulsant medication use 1%, Fried Frailty Index 58%, diabetes 13%, fall once in the previous year 36%, recurrent falls in the previous year 18%

Results Mean total hip BMD at 12 months: 2.8% in zoledronic acid group and 0.5% in placebo group; p< 0.001

Mean total spine BMD at 12 months: 3.0% in zoledronic acid group and 1.1% in placebo group; p= 0.01

Adverse Events Common Adverse Events: zoledronic acid group (98%) vs. placebo group (96%)

Event within three days after infusion: headache (16% vs. 7%), pyrexia (8% vs. 0%), fatigue (24% vs. 15%), arthralgias   (11% vs. 7%), myalgias (8% vs. 3%), influenza-like illness (7% vs.2%), and falls (5% vs. 3%)

Serious Adverse Events: 67% in zoledronic acid group vs. 60% in placebo group

Cardiac disorders: 32% in zoledronic acid group vs. 27% in placebo group

Total fallers: 78% in zoledronic acid vs. 54% in placebo group

Percentage that discontinued due to Adverse Events: not reported
Study Author Conclusions 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. However, prior to changing practice, larger trials are needed to determine whether improvement in these surrogate measures will translate into fracture reduction for vulnerable elderly persons.

Not many studies have been done in frail, elderly patients.  This trial suggests that a single-dose of zoledronic acid infusion may help improve bone density at least for one to two years and may potentially considered for osteoporosis treatment in frail, elderly women.  However, the primary endpoint of the trial was the improvement of BMD, but not clinical fracture reduction.  Further larger trials may be needed to assess the efficacy and safety of zoledronic acid for frail, elderly patients as well as cost effectiveness with lower life expectancy.

References:

  1. National Institute of Arthritis and Musculoskeletal and Skin Diseases. http://www.niams.nih.gov/Health_Info/Bone/Osteoporosis/.   Accessed April 15, 2015.
  2. Gosch M, Jeske M, Kammerlander C, Roth T. Osteoporosis and polypharmacy. Z Gerontol Geriatr. 2012;45(6):450-4. http://www.ncbi.nlm.nih.gov/pubmed/22806642. Accessed April 16, 2015.
  3. Greenspan SL, Perera S, Ferchak MA, Nace DA, Resnick NM. Efficacy and Safety of Single-Dose Zoledronic Acid for Osteoporosis in Frail Elderly Women: A Randomized Clinical Trial. JAMA Intern Med.2015; http://archinte.jamanetwork.com/article.aspx?articleid=2247163&linkId=13508818. Accessed April 15, 2015.
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