Zoledronic Acid Administration in Acute Spinal Cord Injury

Study Overview
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Brief Summary
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In subjects with acute SCI: To compare the effects of parenteral zoledronic acid therapy on preservation of regional and total skeletal mass (DXA). Hypothesis: Zoledronic acid will dramatically diminish bone loss in persons with acute SCI, as evidenced by serial densitometry determinations (DXA).

Detailed Description
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Immobilization is associated with disuse osteoporosis. Spinal cord injury (SCI) produces a syndrome of acute skeletal immobilization with immediate and irreversible unloading of the involved skeletal regions resulting in accelerated bone loss. In addition to rapid bone loss, there are also the complications of hypercalciuria, hypercalcemia, nephrolithiasis, and renal insufficiency. In some reports, as much as 50% of regional bone mass has been lost within the first year after paralysis. A depletion of regional bone of such magnitude greatly increases the risk of fractures, with associated morbidity and increased cost of care. Often, these fractures occur with minimal or non-obvious trauma and may pass undiagnosed for varying lengths of time due to the absence of pain sensation. The acute complications of fracture may include hemorrhage, deep venous thrombosis, and autonomic dysreflexia. Long-term complications include functional deformity, non-union, infection, heterotopic calcification, and significantly longer healing time. The sociology-economic consequences include a minimum of 1 to 2 weeks of hospitalization and the potential need for an increased level of attendant care. This study will address the efficacy of a bisphosphonate, zoledronic acid (Reclast: 5 mg; Novartis Pharmaceuticals Inc., East Hanover, NJ), in the prevention of the bone loss associated with acute SCI. Prevention of regional osteoporosis in persons with SCI would reduce the morbidity associated with fractures, a known secondary complication of immobilization. Thus, the quality of life would be improved in terms of employment responsibilities (reduction in days absent from employment and income lost) and personal activities (recreational endeavors, independence, and ease in which one performs activities of daily living). Individuals with SCI may then engage more securely in activities without fear of fracture, a tremendous psychological benefit.

Official Title
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The Efficacy of Zoledronic Acid in the Prevention of Bone Loss in Acute Spinal Cord Injury

Conditions
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Disuse Osteoporosis

Intervention / Treatment
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* Drug: Zoledronic acid


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Within 3 months of the date of acute SCI. Motor-complete and incomplete SCI [American Spinal Injury Association Impairment Scale (AIS) of sensorimotor impairment (AIS A, B, and C)] Exclusion Criteria: Extensive life-threatening injuries (in addition to SCI) Femur or tibia fracture or extensive bone trauma History of prior bone disease (Paget's disease, overactive parathyroid, osteoporosis) Post-menopausal women Known allergy to bisphosphonates Severe underlying chronic illness Current diagnosis of cancer or history of cancer I am currently receiving corticosteroids Pregnancy or lactation I have been diagnosed with kidney problems As determined from the prescreening blood tests by the study physician Serum creatinine > 2.0 mg/dl As determined from the prescreening blood tests by the study physician Corrected calcium < 8 mg/dl or > 11 mg/dl As determined from the prescreening blood tests by the study physician Elevated liver function enzymes > 2 x upper limit of normal (ULN) I am taking a bisphosphonate for heterotopic ossification (HO) (an overgrowth of bone typically diagnosed shortly after SCI in the pelvic region) I have an existing dental condition or dental infection.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 49 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Zoledronic acid<br>At baseline, study subjects in the treatment group will receive 5 mg of zoledronic acid (Reclast: 5 mg; Novartis Pharmaceuticals Inc., East Hanover, NJ) by intravenous infusion over 30 minutes. | Drug: Zoledronic acid<br>* At baseline, study subjects in the treatment group will receive 5 mg of zoledronic acid (Reclast: 5 mg; Novartis Pharmaceuticals Inc., East Hanover, NJ) by intravenous infusion over 30 minutes.<br>* Other names: Reclast;|
| No Intervention: No Intervention<br>Participants will receive no therapy and serve as a control group and have the same outcome measures completed at parallel time points. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bone Mineral Density (BMD) at the Distal Femur and Proximal Tibia at Baseline and Month 12. | An imaging method known as dual energy x-ray absorptiometry (DXA) was used to obtain BMD of the distal femur and proximal tibia by using a customized research software program supplied by the manufacturer. This measurement will be the primary determinant (dependent measure) of difference among the treatment and control groups, and they will be followed over time at the previously specified time points. | Baseline and 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bone Mineral Density (BMD) at the Total Hip at Baseline and Month 12 | An imaging method known as dual energy x-ray absorptiometry (DXA) was used to obtain BMD of the total hip. | Baseline and 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Spinal Cord Injury, Disuse Osteoporosis, Zoledronic acid, Bisphosphonates, Dual Energy X-ray Absorptiometry