Zoledronic Acid for Osteoporotic Fracture Prevention (ZEST II)

Phase 4

Completed

Interventions: Dietary Supplement: vitamin D
Drug: Zoledronic acid
Dietary Supplement: calcium
Other: Saline

Brief Summary: The goal of this study is to perform the first fracture reduction clinical trial with a potent antiresorptive agent (intravenous zoledronic acid) in the most vulnerable long-term care population.

Detailed Description: Although close to 85% of frail women in long-term care (LTC) facilities have osteoporosis and the risk of osteoporotic fractures is nearly 10 times that of community dwelling elderly, few are treated and studies are scarce. It is postulated that in frail, LTC women an annual infusion of zoledronic acid, an antiresorptive therapy for osteoporosis, will:

1. be effective demonstrated by fracture reduction;

2. be safe.

To address these hypotheses, up to 1000 female LTC residents age 65 and older will be screened in order to enroll 310 eligible for randomization in a 3 year, randomized, double-blind, calcium and vitamin D controlled trial with the antiresorptive agent zoledronic acid. Use of an intravenous, once yearly agent avoids concerns of oral bisphosphonate side effects, poor absorption and burden on staff. Participants will reside in the long-term care settings associated with the Division of Geriatric Medicine, University of Pittsburgh and will include women with multiple comorbid conditions, functional and cognitive impairment, and limited mobility.

Recruitment & Eligibility

Inclusion Criteria

Exclusion Criteria

Men because osteoporosis is less common in men and our initial ZEST 1 study only included women.
Institutionalized women with subacute illnesses surviving or discharged in < 3 years.
Women currently on bisphosphonate, denosumab, or teriparatide therapy or who have been on a bisphosphonate for greater than 1 year during the previous 2 years because bisphosphonates are long acting.
Patients with a calculated creatinine clearance < 35 ml/min or who have a contraindication for bisphosphonates (allergy, hypocalcemia).

Arm && Interventions

Group	Intervention	Description
Placebo Group	vitamin D	Annual dose: intravenous saline; vitamin D (800 IU/daily and calcium (approximately 1200 mg/daily, dietary + supplements)
Placebo Group	calcium	Annual dose: intravenous saline; vitamin D (800 IU/daily and calcium (approximately 1200 mg/daily, dietary + supplements)
Placebo Group	Saline	Annual dose: intravenous saline; vitamin D (800 IU/daily and calcium (approximately 1200 mg/daily, dietary + supplements)
Active Medication Group	vitamin D	Annual dose: intravenous zoledronic acid (Reclast) 5.0 mg; vitamin D (800 IU/daily) and calcium (approximately 1200 mg/daily, dietary + supplements)
Active Medication Group	calcium	Annual dose: intravenous zoledronic acid (Reclast) 5.0 mg; vitamin D (800 IU/daily) and calcium (approximately 1200 mg/daily, dietary + supplements)
Active Medication Group	Zoledronic acid	Annual dose: intravenous zoledronic acid (Reclast) 5.0 mg; vitamin D (800 IU/daily) and calcium (approximately 1200 mg/daily, dietary + supplements)

Primary Outcome Measures

Name	Time	Method
Non-traumatic Incidental Fractures (Vertebral and Nonvertebral [Identified by X-ray, CT, MRI, VFA Imaging] Per Person-year)	3 years	Number of fractures divided by number of person-years. Effectiveness of fracture reduction will be demonstrated by total non-traumatic incidental fractures (vertebral and nonvertebral \[identified by x-ray, CT, MRI, VFA imaging) except those viewed as severe trauma (fall from a height higher than a stool or chair or severe trauma other than a fall), cancer-related or fractures of the toes, finger or facial bones.

Secondary Outcome Measures