Duke Plays Key Role in Fracture Prevention Trial

Large-scale assessment of zoledronic acid among patients with Parkinson’s Disease

Woman has fallen, with hand on the floor

A novel application of zoledronic acid, a bisphosphonate typically prescribed to prevent or treat osteoporosis, is being assessed in a large-scale trial for its potential to prevent fractures in senior patients with Parkinson’s Disease (PD).

Kenneth W. Lyles, MD, a Duke physician scientist and researcher who specializes in metabolic bone disease and geriatric medicine, is medical director of the national Trial of Parkinson’s and Zoledronic Acid (TOPAZ). Duke is an enroller in the trial supported by the National Institute on Aging, a division of the NIH, as well as the Parkinson’s Foundation. The trial tests the efficacy of an IV infusion of Reclast™ (Novartis, East Hanover, NJ).

“This is a very novel trial, and the most compelling aspect is this is one of the first times we’ve undertaken research related to a disease—Parkinson’s Disease—in which we know that if you are over 60 years of age with PD and are not totally bedbound, you have a 10% to 16% chance of a debilitating fracture every year. That fracture rate is too high and should be reduced,” says Lyles, whose research focus is fracture prevention, and who reads bone densities for the Duke Endocrinology, Metabolism and Nutrition Division.

3,500 patients to enroll, with few inclusion criteria

The University of California at San Francisco (UCSF) directs the trial led by Steven Cummings, MD, and Caroline Tanner, MD, PhD, the principal investigators, with the assistance of Sutter Health, a not-for-profit health system based in Sacramento, CA. The goal of the trial, Lyles says, is to assess the effectiveness of the infusion in 3,500 patients with PD.

“The trial is very simple: We want to recruit people over 60 who can walk but are not bedridden and who have Parkinson’s,” Lyles says. “We offer a chance to get either calcium and a little bit of vitamin D, and we’ll come to your home and give you an intravenous infusion of either zoledronic acid or placebo. And then we’re going to monitor your medical record to see if we reduce your risk of disabling fracture.”

Kyle Mitchell, MD, a Duke movement disorder neurologist, says hip fractures related to PD typically result in the loss of independence and often require people to move into a skilled nursing facility to receive the care they need. “I don’t think we as neurologists talk about fracture prevention enough with our patients. This study has already opened my eyes to how common these issues are,” he says.

As a large trial with few inclusion criteria, this novel application is open to not only those with PD but also those with rarer forms of atypical Parkinsonism, for which there are not many studies or treatment options, Mitchell adds.

“As neurologists, we do what we can to prevent falls with physical therapy or assistive devices, and sometimes symptomatic medications can help, but with Parkinson’s, treatment is very much based on style,” he notes. “This study is really looking for whether there is a standard of care that should be applied when it comes to a potentially devastating complication of PD like a hip fracture.”

Participation in trial requires in-home visit

The trial requires an in-home patient visit by a certified mobile research nurse delivering an IV infusion of zoledronic acid, Lyles says. “Obviously, COVID-19 had a significant impact in slowing down participation rates during 2020 because of the reluctance to accept in-home visits, but we are enrolling at a good pace again this year,” he adds. “Clearly, the pandemic affected virtually almost every large clinical trial.”

The Parkinson’s Disease Foundation also recruits patients. Lyles is also on call for patients who experience challenges with the drug. Mitchell is also is part of the trial’s Neurology Steering Committee and recruits Duke patients with PD.

Though the novel application of zoledronic acid may not affect the brain, Mitchell adds, it may help with quality of life and function. “If we’re able to find a drug that can change the course of these illnesses, that would be a huge change in how we treat this disease,” he says.