Patients with Parkinson's disease (PD) have a very high risk of fracture: about 2 to 3-fold increased risk of all fractures and 4-fold increased risk of hip fracture that may be due in large part to their very high risk of multiple falls. Compared with other patients who suffer fractures, PD patients have more severe consequences of fractures: they have twice the risk of dying following hip and pelvic fractures and longer and incomplete functional recovery, with worsening of Parkinson's disease. Crucially, men and women age 65 or older have a fracture risk that is so high, that even those with normal bone density (BMD) for age would warrant a therapy that has been proven to reduce fracture risk in patients with PD. However, very few PD patients age 65 of older receive a treatment for osteoporosis. There are several major barriers to treatment of PD patients with drugs for osteoporosis. 1) There is a lack of evidence that treatments reduce fracture risk in patients with PD whose risk of fractures may be due to multiple and more severe falls. 2) Standard osteoporosis screening and treatment may also be a barrier. Medical visits to assess fracture risk, test BMD, prescribe treatment, generally an oral drug, and then follow-up to monitor compliance and response to treatment, are particularly burdensome for patients with PD. 3) Most patients with PD do not continue taking oral osteoporosis drugs even for 1 year. We propose a randomized trial that addresses all of these barriers. 1) We will test the anti-fracture efficacy of Zoledronic acid (ZA) a very potent bisphosphonate that inhibits bone loss and decreased fracture risk in women with osteoporosis and patients with hip fractures. 2) We will give ZA intravenously at home without clinic visits. 3) ZA inhibits bone loss for at least 2 years overcoming noncompliance with oral drugs. We will enroll 3,500 men and women PD age 65 years or older from large health systems, patient communities, and referrals from neurologists in the Parkinson's Study Group. A movement disorders specialist will confirm the diagnosis of PD by telemedicine. We will then provide calcium and vitamin D supplements. A research nurse will visit the patient at home, check for potential contraindications to ZA and then administer IV ZA or placebo. We will then follow patients for 2 years to ascertain and confirm fractures. A successful result may revolutionize the care of patients with PD. It may lead to guidelines promoting home-based ZA treatment of older PD patients. ZA, rather than oral drugs, would become the 1st line treatment for patients with PD. The trial would demonstrate that home-based treatment with ZA, without other assessments, could reach all older PD patients without the need for burdensome medical visits. Thus, a positive result may lead to treatment of many more PD patients and a substantial reduction in the occurrence of disabling fractures in patients with PD.
Patients with Parkinson's disease have a high risk of falls and fractures but few receive treatment. In a nation- wide trial, we will test whether intravenous zoledronic acid given at home reduces that risk without burdensome clinic visits. If so, this home-based treatment could be widely use to reduce fractures in these patients.
