Zoledronic Acid for Osteoporotic Fracture Prevention (ZEST II)

Susan L. Greenspan

Status and phase: Completed; Phase 4

Conditions: Osteoporotic Fractures; Osteoporosis, Postmenopausal

Treatments: Drug: Zoledronic acid; Dietary Supplement: vitamin D; Other: Saline; Dietary Supplement: calcium

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT02589600

STUDY19040149 (ZEST II)

1R01AG050302-01A1 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 310 patients

Sex: Female

Ages: 65+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• women age ≥65 years including those using assistive devices to maximize generalizability if they:

  1. Reside in long-term care (LTC);

  2. Have:

     • osteoporosis by axial bone density (spine, hip or forearm bone mineral density (BMD) T-score ≤ -2.5 SD); or
     • a previous adult fragility fracture of the spine or hip; or,
     • would be treated based on FRAX National Osteoporosis Foundation (NOF) treatment thresholds of a 10 year risk of ≥ 20% for a major osteoporotic fracture or ≥ 3% for hip fracture using femoral neck BMD.

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).

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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310 participants in 2 patient groups, including a placebo group

Active Medication Group

Experimental group

Description:

Annual dose: intravenous zoledronic acid (Reclast) 5.0 mg; vitamin D (800 IU/daily) and calcium (approximately 1200 mg/daily, dietary + supplements)

Treatment:

Drug: Zoledronic acid

Dietary Supplement: vitamin D

Dietary Supplement: calcium

Placebo Group

Placebo Comparator group

Description:

Annual dose: intravenous saline; vitamin D (800 IU/daily and calcium (approximately 1200 mg/daily, dietary + supplements)

Treatment:

Dietary Supplement: vitamin D

Dietary Supplement: calcium

Other: Saline