TOPAZ: Trial of Parkinson's and Zoledronic Acid. A Randomized Placebo-controlled Trial of Zoledronic Acid for Prevention of Fractures in Patients with Parkinson's Disease

The Trial of Parkinson's And Zoledronic acid (TOPAZ), a large, pragmatic, home-based, randomized, placebo-controlled, double-blind clinical trial designed to test whether a single intravenous infusion of zoledronic acid can reduce fracture risk in people with neurodegenerative parkinsonism.

TOPAZ arose from the recognition that people with Parkinson's disease and related parkinsonisms have markedly increased risk of falls and fractures, with studies demonstrating substantially elevated risks of hip and other fractures compared with the general population. Fractures in this population lead to sustained disability and increased mortality, yet only a small proportion of people with parkinsonism receive treatments to reduce fracture risk. Barriers to treatment include uncertainty about efficacy in this population whose fractures may be driven by falls, burdensome conventional assessment pathways that require bone mineral density (BMD) testing and specialist evaluation unfamiliar to many neurologists, and poor adherence to oral osteoporosis therapies among older adults taking multiple medications. TOPAZ is a collaboration between experts in movement disorders and osteoporosis intending to enroll 3,500 participants aged 65 years or older across the United States without geographic limits. 

The trial is novel in its direct-to-consumer, home-based design: recruitment and enrollment are open to people regardless of whether they receive specialty care, and participation can be completed entirely from home. The protocol leverages online consent technology, telemedicine assessments to confirm parkinsonism diagnoses, and research nursing capable of performing medical screening and administering a parenteral infusion in participants’ homes. This model is intended to reduce cost, increase convenience, broaden access, and open trial participation to individuals who would otherwise face barriers related to travel, mobility, or lack of specialty care. Clinically, TOPAZ tests a pragmatic therapeutic approach: administering zoledronic acid, an FDA-approved parenteral bisphosphonate shown in prior trials to improve BMD and reduce fractures in postmenopausal women with osteoporosis and in men and women after hip fracture. Zoledronic acid’s anti-fracture benefits and effects on BMD have been observed to persist for at least two years after a single infusion, and the drug can be delivered safely in the home by trained nursing staff. TOPAZ’s design deliberately avoids requiring BMD testing for trial entry, informed by analyses indicating that zoledronic acid’s efficacy for fracture reduction did not depend on baseline BMD in prior datasets. Participants may, however, opt to pursue BMD testing and conventional evaluation instead of trial participation if they prefer.

If TOPAZ demonstrates a reduction in fracture risk among older adults with parkinsonism, the implications for clinical practice would be substantial: zoledronic acid could be recommended broadly for people age 65 or older with Parkinson's disease or related parkinsonisms who have no contraindications, without need for routine BMD screening prior to treatment. Beyond the specific therapeutic question, TOPAZ serves as a test case for conducting large-scale, inclusive, home-based clinical research using telemedicine, remote consent, and in-home clinical procedures. The trial highlights opportunities to reach patients who are geographically dispersed or not engaged with specialty clinics and suggests a scalable approach to clinical trials for populations with mobility limitations. TOPAZ thus addresses both an important clinical question about fracture prevention in parkinsonism and a methodological question about how to make clinical research more accessible and efficient for vulnerable patient populations.