Bone Loss, Fragility Fractures, Osteoporosis
Conditions
Keywords
Osteoporosis, Bone loss, Frail Geriatric Women, Nursing Home Patients, Fragility Fractures
Brief summary
This trial will examine the safety, efficacy and feasibility of a single dose of intravenous zoledronic acid in the maintenance of skeletal integrity for frail, institutionalized women, who are most at risk for the deleterious outcomes of osteoporosis. The investigators will test the hypothesis that in institutionalized elderly women a single dose of intravenous zoledronic acid therapy will: (1) be efficacious as demonstrated by stability or improvement in bone mass measurements and reductions in bone turnover; (2) be safe and feasible; and (3) provide estimates for vertebral and nonvertebral fracture reduction in this cohort for use in planning a future study.
Detailed description
This is a 2-year, randomized, double-blind, calcium/vitamin D-controlled clinical trial of a single dose of therapy with at least 12 months follow-up. All participants will receive calcium and vitamin D throughout the trial. At baseline, 190 women will be randomized in a 1:1 allocation to zoledronic acid (group 1) or zoledronic acid placebo (group 2). At the end of 24 months, women will be followed to gather data on longer term fragility fracture rates and survival until all participants have completed 24 months of follow-up.
Interventions
DRUGIntravenous zoledronic acid
Intravenous zoledronic acid 5.0 mg once
DIETARY_SUPPLEMENTVitamin D 800 IU/daily
Daily divided dose
DIETARY_SUPPLEMENTCalcium 1200 mg/daily
supplement plus diet
Sponsors
National Institutes of Health (NIH)
National Institute on Aging (NIA)
University of Pittsburgh
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
* We will include elderly women 65 years and older if they reside in a nursing home or an assisted living facility and have a known history of osteoporosis, as determined by history of an adult fragility fracture or bone mineral density criteria for osteoporosis (T-score -2.5 at the total hip, femoral neck or spine) or low bone mass (T-score \< -2.0 at the total hip, femoral neck or spine, consistent with the National Osteoporosis Foundation Treatment guidelines). If a participant's spine and or hip are not evaluable (due to surgery, calcifications, artifact in the scan area, scoliosis, etc.), they may be included in the study with a T-score of ≤ -2.0 at the forearm. * Elders will be chosen without consideration of ethnic or racial background. We chose frail, institutionalized women because 70-85% of them have osteoporosis and this age group is substantially under-treated. * We will include all who qualify, if they are able to weight bear or assist with transfer to chair, to endure that the results have maximum generalizability to the nursing home population as a whole.
Exclusion criteria
* Children will be excluded because they are not frail, institutionalized elders. * Men will be excluded because they do not become postmenopausal and are less likely to become osteoporotic. * We will exclude institutionalized women with subacute illnesses who are not expected to survive or who will be discharged in less than 2 years. * We will also exclude patient with a contraindication to bisphosphonate, such as hypocalcemia, allergy, pervious adverse event (excluding gastrointestinal disorders), or currently on an oral bisphosphonate. * We will exclude patients with a calculated creatinine clearance of \< 30 ml/mm. * We will exclude women scheduled for or in need of a tooth extraction as this procedure has been associated with osteonecrosis of the jaw in patients with cancer given multiple coursed of high dose intravenous bisphosphonates. * We will screen for these conditions by detailed history, physical exam (including dental exam), chart review, and baseline laboratory analyses, including BUN/creatinine, liver function tests, TSH, calcium, PTH, 25-hydroxyvitamin D, alkaline phosphatase and baseline calculated creatinine clearance. Participants with vitamin D levels \< 20 ng/ml will be treated with vitamin D 50,000 IU/wk for 8 weeks in addition to calcium. Vitamin D will be rechecked and the patient will be enrolled if the vitamin D level is \> 20 ng/ml. * Patients will be allowed to continue on certain medications known to affect bone and mineral metabolism (e.g. glucocorticoids, anticonvulsants) because their use is common in this population. (In our facilities, 2.9% of patients use glucocorticoids and 7.2% use anti-epileptic drugs.) In addition, women who have been treated in the past or present with osteoporosis agents, such as estrogen/progesterone, raloxifene, and calcitonin, will be allowed to participate and continue on these therapies if prescribed by their physician. However, if patients are currently on or have been on bisphosphonates for greater than 1 year in the previous 2 years prior to enrollment, they will be excluded as some bisphosphonates are long acting. * Patients will be allowed to wear hip pads if prescribed by their physician. If they are on parathyroid hormone, they may participate, but will be told that monotherapy with parathyroid hormone is more beneficial than combination therapy with parathyroid hormone and alendronate, as we have previously demonstrated.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Bone Mineral Density (BMD) of the Total Hip and Spine | Baseline, 12 months, 24 month | BMD is the bone mineral density of the lumbar spine and total hip measured using dual-energy xray absorptiometry (DXA) scan |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Active Medication Group One-time dose: Intravenous Zoledronic Acid 5.0 mg
Intravenous zoledronic acid: Intravenous zoledronic acid 5.0 mg once | 89 |
| Placebo Placebo
Intravenous zoledronic acid: Intravenous zoledronic acid 5.0 mg once | 92 |
| Total | 181 |
Baseline characteristics
| Characteristic | Active Medication Group | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 89 Participants | 92 Participants | 181 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment United States | 89 participants | 92 participants | 181 participants |
| Sex: Female, Male Female | 89 Participants | 92 Participants | 181 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 | — / — | — / — |
| other Total, other adverse events | 87 / 89 | 88 / 92 |
| serious Total, serious adverse events | 60 / 89 | 55 / 92 |
Outcome results
Primary
Bone Mineral Density (BMD) of the Total Hip and Spine
BMD is the bone mineral density of the lumbar spine and total hip measured using dual-energy xray absorptiometry (DXA) scan
Time frame: Baseline, 12 months, 24 month
Population: Number of patients that completed a DXA at 12 months. At 24 months 60 in active treatment group and 72 in placebo group completed a DXA.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Active Medication Group | Bone Mineral Density (BMD) of the Total Hip and Spine | Spine BMD at 24 months | 4.5 Percent change | Standard Error 0.8 |
| Active Medication Group | Bone Mineral Density (BMD) of the Total Hip and Spine | Total Hip BMD at 24 months | 2.6 Percent change | Standard Error 0.6 |
| Active Medication Group | Bone Mineral Density (BMD) of the Total Hip and Spine | Total Hip BMD at 12 months | 2.8 Percent change | Standard Error 0.5 |
| Active Medication Group | Bone Mineral Density (BMD) of the Total Hip and Spine | Spine BMD at 12 months | 3.0 Percent change | Standard Error 0.5 |
| Placebo | Bone Mineral Density (BMD) of the Total Hip and Spine | Total Hip BMD at 12 months | -0.5 Percent change | Standard Error 0.4 |
| Placebo | Bone Mineral Density (BMD) of the Total Hip and Spine | Spine BMD at 24 months | 0.7 Percent change | Standard Error 0.5 |
| Placebo | Bone Mineral Density (BMD) of the Total Hip and Spine | Spine BMD at 12 months | 1.1 Percent change | Standard Error 0.5 |
| Placebo | Bone Mineral Density (BMD) of the Total Hip and Spine | Total Hip BMD at 24 months | -1.5 Percent change | Standard Error 0.7 |