Zoledronic Acid for Osteoporosis in the Elderly

NCT00558012 | Completed Results DMC

• 2 other identifiers: 0612018R01AG028086-01A1
• Study Type: interventional
• Target: 181
• Locations: 1 country
• Sites: 1

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.

Conditions

Osteoporosis; Bone Loss; Fragility Fractures

Keywords

Osteoporosis; Bone loss; Frail Geriatric Women; Nursing Home Patients; Fragility Fractures

Outcome Measures

Primary Outcomes (1)

• 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

  Baseline, 12 months, 24 month

Study Arms (2)

Active Medication Group

EXPERIMENTAL

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; Dietary Supplement: Vitamin D 800 IU/daily; Dietary Supplement: Calcium 1200 mg/daily

Placebo

PLACEBO COMPARATOR

One-time dose: intravenous saline; Vitamin D (800 IU/daily); 1200 mg calcium (supplement plus diet)

Drug: Intravenous zoledronic acid; Dietary Supplement: Vitamin D 800 IU/daily; Dietary Supplement: Calcium 1200 mg/daily

Interventions

Intravenous zoledronic acid DRUG

Intravenous zoledronic acid 5.0 mg once

Also known as: Zometa, Reclast

Active Medication Group; Placebo

Vitamin D 800 IU/daily DIETARY_SUPPLEMENT

Daily divided dose

Active Medication Group; Placebo

Calcium 1200 mg/daily DIETARY_SUPPLEMENT

supplement plus diet

Active Medication Group; Placebo

Eligibility Criteria

• Age: 65 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Pittsburgh: lead
• National Institutes of Health (NIH): collaborator
• National Institute on Aging (NIA): collaborator

Study Sites (1)

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15213, United States

Location

Related Publications (1)

• Greenspan SL, Perera S, Ferchak MA, Nace DA, Resnick NM. Efficacy and safety of single-dose zoledronic acid for osteoporosis in frail elderly women: a randomized clinical trial. JAMA Intern Med. 2015 Jun;175(6):913-21. doi: 10.1001/jamainternmed.2015.0747.

  PMID: 25867538 DERIVED

MeSH Terms

Conditions

Osteoporosis; Bone Diseases, Metabolic

Interventions

Zoledronic Acid; Vitamin D; Calcium

Condition Hierarchy (Ancestors)

Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Diphosphonates; Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Secosteroids; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Metals, Alkaline Earth; Elements; Inorganic Chemicals; Metals; Blood Coagulation Factors; Biological Factors

Results Point of Contact

• Title: Dr. Susan Greenspan
• Organization: University of Pittsburgh

greenspn@pitt.edu

412-692-2477

Study Officials

• Susan L Greenspan, MD

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 13, 2007
• First Posted: November 14, 2007
• Study Start: December 1, 2007
• Primary Completion: February 1, 2014
• Study Completion: February 1, 2014
• Last Updated: July 31, 2015
• Results First Posted: July 8, 2015

Record last verified: 2015-07

Locations

US (1)