Osteoporosis, Postmenopausal, Osteoporotic Fractures
Conditions
Keywords
Bone loss, Frail Geriatric Women, Nursing Home Patients, Long-term Care Patients, Osteoporosis, Osteoporotic Fractures
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.
Interventions
DRUGZoledronic acid
Annual intravenous 5.0 mg
DIETARY_SUPPLEMENTvitamin D
800 IU daily
DIETARY_SUPPLEMENTcalcium
approximately 1200 mg (dietary and supplement)
OTHERSaline
Annual intravenous saline placebo
Sponsors
National Institutes of Health (NIH)
National Institute on Aging (NIA)
Susan L. Greenspan
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
65 Years to No maximum
Healthy volunteers
No
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Participant flow
Recruitment details
Recruitment will occur during the first 2 years of the grant cycle and take place in the determined long term care facilities.
Pre-assignment details
310 subjects were consented, randomized and received the study drug.
Participants by arm
| Arm | Count |
|---|---|
| Active Medication Group Annual dose: intravenous zoledronic acid (Reclast) 5.0 mg; vitamin D (800 IU/daily) and calcium (approximately 1200 mg/daily, dietary + supplements)
Zoledronic acid: Annual intravenous 5.0 mg
vitamin D: 800 IU daily
calcium: approximately 1200 mg (dietary and supplement) | 154 |
| Placebo Group Annual dose: intravenous saline; vitamin D (800 IU/daily and calcium (approximately 1200 mg/daily, dietary + supplements)
vitamin D: 800 IU daily
calcium: approximately 1200 mg (dietary and supplement)
Saline: Annual intravenous saline placebo | 156 |
| Total | 310 |
Baseline characteristics
| Characteristic | Active Medication Group | Placebo Group | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 154 Participants | 156 Participants | 310 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 81.3 years STANDARD_DEVIATION 7.9 | 79.9 years STANDARD_DEVIATION 7.7 | 80.6 years STANDARD_DEVIATION 7.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 1 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 151 Participants | 155 Participants | 306 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 11 Participants | 10 Participants | 21 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 142 Participants | 146 Participants | 288 Participants |
| Region of Enrollment United States | 154 participants | 156 participants | 310 participants |
| Sex: Female, Male Female | 154 Participants | 156 Participants | 310 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 13 / 154 | 19 / 156 |
| other Total, other adverse events | 131 / 154 | 130 / 156 |
| serious Total, serious adverse events | 73 / 154 | 80 / 156 |
Outcome results
Primary
Non-traumatic Incidental Fractures (Vertebral and Nonvertebral [Identified by X-ray, CT, MRI, VFA Imaging] Per Person-year)
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.
Time frame: 3 years
Population: Women age 65 years and older
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Active Medication Group | Non-traumatic Incidental Fractures (Vertebral and Nonvertebral [Identified by X-ray, CT, MRI, VFA Imaging] Per Person-year) | 1.06093 Fractures per person-year |
| Placebo Group | Non-traumatic Incidental Fractures (Vertebral and Nonvertebral [Identified by X-ray, CT, MRI, VFA Imaging] Per Person-year) | 1.01563 Fractures per person-year |
p-value: 0.725195% CI: [0.9, 1.22]Negative binomial regression