ZEST: Zoledronic Acid for Osteoporosis in the Elderly
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
N/A |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Active Medication Group One-time dose: Intravenous Zoledronic Acid 5.0 mg; Vitamin D (800 IU/daily); Calcium 1200 mg/daily (supplement plus diet) |
Drug: Intravenous zoledronic acid
Intravenous zoledronic acid 5.0 mg once
Other Names:
Dietary Supplement: Vitamin D 800 IU/daily
Daily divided dose
Dietary Supplement: Calcium 1200 mg/daily
supplement plus diet
|
| Placebo Comparator: Placebo One-time dose: intravenous saline; Vitamin D (800 IU/daily); 1200 mg calcium (supplement plus diet) |
Drug: Intravenous zoledronic acid
Intravenous zoledronic acid 5.0 mg once
Other Names:
Dietary Supplement: Vitamin D 800 IU/daily
Daily divided dose
Dietary Supplement: Calcium 1200 mg/daily
supplement plus diet
|
Outcome Measures
Primary Outcome Measures
- 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
Eligibility Criteria
Criteria
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of Pittsburgh Medical Center | Pittsburgh | Pennsylvania | United States | 15213 |
Sponsors and Collaborators
- University of Pittsburgh
- National Institutes of Health (NIH)
- National Institute on Aging (NIA)
Investigators
- Principal Investigator: Susan L Greenspan, MD, University of Pittsburgh
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 0612018
- R01AG028086-01A1
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Active Medication Group | Placebo |
|---|---|---|
| Arm/Group Description | One-time dose: Intravenous Zoledronic Acid 5.0 mg Intravenous zoledronic acid: Intravenous zoledronic acid 5.0 mg once | Placebo One-time dose: Intravenous saline |
| Period Title: Overall Study | ||
| STARTED | 89 | 92 |
| COMPLETED | 64 | 74 |
| NOT COMPLETED | 25 | 18 |
Baseline Characteristics
| Arm/Group Title | Active Medication Group | Placebo | Total |
|---|---|---|---|
| Arm/Group Description | One-time dose: Intravenous Zoledronic Acid 5.0 mg Intravenous zoledronic acid: Intravenous zoledronic acid 5.0 mg once | Placebo Intravenous zoledronic acid: Intravenous zoledronic acid 5.0 mg once | Total of all reporting groups |
| Overall Participants | 89 | 92 | 181 |
| Age (Count of Participants) | |||
| <=18 years |
0
0%
|
0
0%
|
0
0%
|
| Between 18 and 65 years |
0
0%
|
0
0%
|
0
0%
|
| >=65 years |
89
100%
|
92
100%
|
181
100%
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
89
100%
|
92
100%
|
181
100%
|
| Male |
0
0%
|
0
0%
|
0
0%
|
| Region of Enrollment (participants) [Number] | |||
| United States |
89
100%
|
92
100%
|
181
100%
|
Outcome Measures
| Title | Bone Mineral Density (BMD) of the Total Hip and Spine |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Active Medication Group | Placebo |
|---|---|---|
| Arm/Group Description | One-time dose: Intravenous Zoledronic Acid 5.0 mg Intravenous zoledronic acid: Intravenous zoledronic acid 5.0 mg once | Placebo Intravenous zoledronic acid: Intravenous zoledronic acid 5.0 mg once |
| Measure Participants | 75 | 83 |
| Spine BMD at 24 months |
4.5
(0.8)
|
0.7
(0.5)
|
| Spine BMD at 12 months |
3.0
(0.5)
|
1.1
(0.5)
|
| Total Hip BMD at 24 months |
2.6
(0.6)
|
-1.5
(0.7)
|
| Total Hip BMD at 12 months |
2.8
(0.5)
|
-0.5
(0.4)
|
Adverse Events
| Time Frame | 2 years | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | ||||
| Arm/Group Title | Active Medication Group | Placebo | ||
| Arm/Group Description | One-time dose: Intravenous Zoledronic Acid 5.0 mg Intravenous zoledronic acid: Intravenous zoledronic acid 5.0 mg once | Placebo Intravenous zoledronic acid: Intravenous zoledronic acid 5.0 mg once | ||
All Cause Mortality |
||||
| Active Medication Group | Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| Active Medication Group | Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 60/89 (67.4%) | 55/92 (59.8%) | ||
| Cardiac disorders | ||||
| Atrial fibrillation | 3/89 (3.4%) | 3/92 (3.3%) | ||
| Cardiac failure congestive | 6/89 (6.7%) | 3/92 (3.3%) | ||
| Chest pain | 1/89 (1.1%) | 7/92 (7.6%) | ||
| Myocardial infarction | 2/89 (2.2%) | 1/92 (1.1%) | ||
| Oedema perepheral | 1/89 (1.1%) | 0/92 (0%) | ||
| Sick sinus syndrome | 0/89 (0%) | 1/92 (1.1%) | ||
| Ventricular tachycardia | 0/89 (0%) | 1/92 (1.1%) | ||
| Eye disorders | ||||
| choroid melanoma | 1/89 (1.1%) | 0/92 (0%) | ||
| Gastrointestinal disorders | ||||
| Abdominal hernia | 0/89 (0%) | 1/92 (1.1%) | ||
| Abdominal pain | 1/89 (1.1%) | 0/92 (0%) | ||
| Clostridium difficile colitis | 1/89 (1.1%) | 1/92 (1.1%) | ||
| Colitis | 0/89 (0%) | 1/92 (1.1%) | ||
| Diarrhea | 1/89 (1.1%) | 2/92 (2.2%) | ||
| Diverticulitis | 0/89 (0%) | 1/92 (1.1%) | ||
| Gastric ulcer | 0/89 (0%) | 1/92 (1.1%) | ||
| Gastoenteritis | 1/89 (1.1%) | 1/92 (1.1%) | ||
| Gastrointestinal haemorrhage | 3/89 (3.4%) | 1/92 (1.1%) | ||
| Gastriesophageal reflux disease | 0/89 (0%) | 1/92 (1.1%) | ||
| Haematochezia | 0/89 (0%) | 1/92 (1.1%) | ||
| Lower gastrointestinal haemorrhage | 1/89 (1.1%) | 0/92 (0%) | ||
| Oesophagitis | 0/89 (0%) | 1/92 (1.1%) | ||
| Pancreatic mass | 0/89 (0%) | 1/92 (1.1%) | ||
| Pancreatitis | 0/89 (0%) | 1/92 (1.1%) | ||
| Proctitis ulcerative | 1/89 (1.1%) | 0/92 (0%) | ||
| Rectal haemorrhage | 0/89 (0%) | 2/92 (2.2%) | ||
| Vomiting | 1/89 (1.1%) | 0/92 (0%) | ||
| General disorders | ||||
| Death | 8/89 (9%) | 3/92 (3.3%) | ||
| Hepatobiliary disorders | ||||
| Hepatic cirrhosis | 1/89 (1.1%) | 0/92 (0%) | ||
| Infections and infestations | ||||
| Bronchitis | 3/89 (3.4%) | 1/92 (1.1%) | ||
| Herpes zoster | 1/89 (1.1%) | 0/92 (0%) | ||
| Pneumonia | 8/89 (9%) | 5/92 (5.4%) | ||
| Injury, poisoning and procedural complications | ||||
| Contusion | 0/89 (0%) | 1/92 (1.1%) | ||
| Fall | 4/89 (4.5%) | 4/92 (4.3%) | ||
| Head injury | 1/89 (1.1%) | 0/92 (0%) | ||
| Post traumatic pain | 0/89 (0%) | 1/92 (1.1%) | ||
| Investigations | ||||
| Blood glucose increased | 0/89 (0%) | 1/92 (1.1%) | ||
| Sepsis | 0/89 (0%) | 1/92 (1.1%) | ||
| Metabolism and nutrition disorders | ||||
| Dehydration | 1/89 (1.1%) | 2/92 (2.2%) | ||
| Hyponatraemia | 0/89 (0%) | 1/92 (1.1%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Back pain | 2/89 (2.2%) | 0/92 (0%) | ||
| Femur fracture | 0/89 (0%) | 1/92 (1.1%) | ||
| Fractured sacrum | 0/89 (0%) | 1/92 (1.1%) | ||
| Gouty arthritis | 1/89 (1.1%) | 0/92 (0%) | ||
| Hip fracture | 1/89 (1.1%) | 1/92 (1.1%) | ||
| Muscular weakness | 2/89 (2.2%) | 0/92 (0%) | ||
| Myalgia | 0/89 (0%) | 1/92 (1.1%) | ||
| Pubic rami fracture | 1/89 (1.1%) | 0/92 (0%) | ||
| Tibia fracture | 1/89 (1.1%) | 0/92 (0%) | ||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Breast cancer | 0/89 (0%) | 1/92 (1.1%) | ||
| Lung cancer metastatic | 0/89 (0%) | 1/92 (1.1%) | ||
| Nervous system disorders | ||||
| Cerebellar infarction | 1/89 (1.1%) | 0/92 (0%) | ||
| Cerebrovascular accident | 2/89 (2.2%) | 1/92 (1.1%) | ||
| Confusional state | 1/89 (1.1%) | 0/92 (0%) | ||
| Dementia Alzheimers type | 0/89 (0%) | 1/92 (1.1%) | ||
| Lethargy | 1/89 (1.1%) | 0/92 (0%) | ||
| Loss of consciousness | 1/89 (1.1%) | 0/92 (0%) | ||
| Mental impairment | 3/89 (3.4%) | 2/92 (2.2%) | ||
| Relapsing-remitting multiple sclerosis | 1/89 (1.1%) | 0/92 (0%) | ||
| Subarachnoid haemorrhage | 1/89 (1.1%) | 0/92 (0%) | ||
| Syncope | 0/89 (0%) | 1/92 (1.1%) | ||
| Transient ischemic attack | 3/89 (3.4%) | 4/92 (4.3%) | ||
| Tremor | 1/89 (1.1%) | 0/92 (0%) | ||
| Renal and urinary disorders | ||||
| Renal failure acute | 0/89 (0%) | 1/92 (1.1%) | ||
| Urinary tract infection | 4/89 (4.5%) | 4/92 (4.3%) | ||
| Urosepsis | 1/89 (1.1%) | 1/92 (1.1%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Aspiration | 0/89 (0%) | 1/92 (1.1%) | ||
| Asthma | 1/89 (1.1%) | 0/92 (0%) | ||
| Chronic obstructive pulmonary disease | 4/89 (4.5%) | 3/92 (3.3%) | ||
| Dyspnoea | 2/89 (2.2%) | 3/92 (3.3%) | ||
| Epistaxis | 0/89 (0%) | 1/92 (1.1%) | ||
| Pleural effusion | 1/89 (1.1%) | 1/92 (1.1%) | ||
| Pneumothorax | 0/89 (0%) | 1/92 (1.1%) | ||
| Pulmonary oedema | 1/89 (1.1%) | 0/92 (0%) | ||
| Skin and subcutaneous tissue disorders | ||||
| Cellulitis | 4/89 (4.5%) | 1/92 (1.1%) | ||
| Decubitus ulcer | 0/89 (0%) | 1/92 (1.1%) | ||
| Surgical and medical procedures | ||||
| Arterial bypass operation | 0/89 (0%) | 1/92 (1.1%) | ||
| Hip arthroplasty | 0/89 (0%) | 1/92 (1.1%) | ||
| Knee arthroplast | 1/89 (1.1%) | 2/92 (2.2%) | ||
| Shoulder arthroplasty | 0/89 (0%) | 2/92 (2.2%) | ||
| Vascular disorders | ||||
| Aortic aneurysm | 0/89 (0%) | 1/92 (1.1%) | ||
| Arteriosclerosis | 0/89 (0%) | 2/92 (2.2%) | ||
| Colitis ischaemic | 0/89 (0%) | 1/92 (1.1%) | ||
| Deep vein thrombosis | 1/89 (1.1%) | 0/92 (0%) | ||
| Essential hypertension | 1/89 (1.1%) | 0/92 (0%) | ||
| Hypertension | 2/89 (2.2%) | 0/92 (0%) | ||
| Hypertensive crisis | 0/89 (0%) | 1/92 (1.1%) | ||
| Labile blood pressure | 1/89 (1.1%) | 0/92 (0%) | ||
| Orthostatic hypotension | 1/89 (1.1%) | 0/92 (0%) | ||
| Pulmonary embolism | 1/89 (1.1%) | 0/92 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Active Medication Group | Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 87/89 (97.8%) | 88/92 (95.7%) | ||
| Cardiac disorders | ||||
| Atrial fibrillation | 5/89 (5.6%) | 5/92 (5.4%) | ||
| Cardiac failure congestive | 8/89 (9%) | 4/92 (4.3%) | ||
| Chest pain | 8/89 (9%) | 12/92 (13%) | ||
| Oedema peripheral | 5/89 (5.6%) | 5/92 (5.4%) | ||
| Gastrointestinal disorders | ||||
| Diarrhea | 7/89 (7.9%) | 12/92 (13%) | ||
| Nausea | 13/89 (14.6%) | 7/92 (7.6%) | ||
| General disorders | ||||
| Death | 8/89 (9%) | 3/92 (3.3%) | ||
| Fatigue | 24/89 (27%) | 14/92 (15.2%) | ||
| Influenza-like illness | 6/89 (6.7%) | 2/92 (2.2%) | ||
| Pyrexia | 8/89 (9%) | 1/92 (1.1%) | ||
| Infections and infestations | ||||
| Bronchitis | 6/89 (6.7%) | 3/92 (3.3%) | ||
| Pneumonia | 12/89 (13.5%) | 9/92 (9.8%) | ||
| Injury, poisoning and procedural complications | ||||
| Contusion | 5/89 (5.6%) | 13/92 (14.1%) | ||
| Fall | 69/89 (77.5%) | 54/92 (58.7%) | ||
| Infusion site bruising | 11/89 (12.4%) | 12/92 (13%) | ||
| Post traumatic pain | 5/89 (5.6%) | 5/92 (5.4%) | ||
| Skin laceration | 8/89 (9%) | 10/92 (10.9%) | ||
| Metabolism and nutrition disorders | ||||
| Anorexia | 5/89 (5.6%) | 3/92 (3.3%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Arthralgia | 12/89 (13.5%) | 7/92 (7.6%) | ||
| Back pain | 4/89 (4.5%) | 5/92 (5.4%) | ||
| Muscular weakness | 6/89 (6.7%) | 0/92 (0%) | ||
| Myalgia | 8/89 (9%) | 6/92 (6.5%) | ||
| Pain in extremity | 10/89 (11.2%) | 7/92 (7.6%) | ||
| Nervous system disorders | ||||
| Headache | 14/89 (15.7%) | 8/92 (8.7%) | ||
| Transient ischemic attack | 3/89 (3.4%) | 5/92 (5.4%) | ||
| Renal and urinary disorders | ||||
| Urinary tract infection | 16/89 (18%) | 20/92 (21.7%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Dyspnoea | 5/89 (5.6%) | 7/92 (7.6%) | ||
| Skin and subcutaneous tissue disorders | ||||
| Cellulitis | 9/89 (10.1%) | 7/92 (7.6%) | ||
| Surgical and medical procedures | ||||
| Tooth extraction | 4/89 (4.5%) | 5/92 (5.4%) | ||
| Vascular disorders | ||||
| Ecchymosis | 1/89 (1.1%) | 5/92 (5.4%) | ||
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Dr. Susan Greenspan |
|---|---|
| Organization | University of Pittsburgh |
| Phone | 412-692-2477 |
| greenspn@pitt.edu |
- 0612018
- R01AG028086-01A1