Zoledronic Acid Administration in Acute Spinal Cord Injury

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

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).

Study Overview

• Status: Completed
• Conditions: Disuse Osteoporosis
• Intervention / Treatment: Drug: Zoledronic acid

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • New Jersey
    • West Orange, New Jersey, United States, 07052
      • Kessler Institute for Rehabilitation

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 49 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Within 3 months of the date of acute SCI.
2. Motor-complete and incomplete SCI [American Spinal Injury Association Impairment Scale (AIS) of sensorimotor impairment (AIS A, B, and C)]

Exclusion Criteria:

1. Extensive life-threatening injuries (in addition to SCI)
2. Femur or tibia fracture or extensive bone trauma
3. History of prior bone disease (Paget's disease, overactive parathyroid, osteoporosis)
4. Post-menopausal women
5. Known allergy to bisphosphonates
6. Severe underlying chronic illness
7. Current diagnosis of cancer or history of cancer
8. I am currently receiving corticosteroids
9. Pregnancy or lactation
10. I have been diagnosed with kidney problems
11. As determined from the prescreening blood tests by the study physician Serum creatinine > 2.0 mg/dl
12. As determined from the prescreening blood tests by the study physician Corrected calcium < 8 mg/dl or > 11 mg/dl
13. As determined from the prescreening blood tests by the study physician Elevated liver function enzymes > 2 x upper limit of normal (ULN)
14. I am taking a bisphosphonate for heterotopic ossification (HO) (an overgrowth of bone typically diagnosed shortly after SCI in the pelvic region)
15. I have an existing dental condition or dental infection.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Zoledronic acid; 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; 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.; Other Names: Reclast; Zometa
NO_INTERVENTION: No Intervention; 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?

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

Collaborators and Investigators

• Sponsor: James J. Peters Veterans Affairs Medical Center
• Collaborators: Kessler Institute for Rehabilitation

Publications and helpful links

General Publications

• Shapiro J, Smith B, Beck T, Ballard P, Dapthary M, BrintzenhofeSzoc K, Caminis J. Treatment with zoledronic acid ameliorates negative geometric changes in the proximal femur following acute spinal cord injury. Calcif Tissue Int. 2007 May;80(5):316-22. doi: 10.1007/s00223-007-9012-6. Epub 2007 Apr 7.
• Bubbear JS, Gall A, Middleton FR, Ferguson-Pell M, Swaminathan R, Keen RW. Early treatment with zoledronic acid prevents bone loss at the hip following acute spinal cord injury. Osteoporos Int. 2011 Jan;22(1):271-9. doi: 10.1007/s00198-010-1221-6. Epub 2010 Apr 1.

Study record dates

Study Major Dates

• Study Start: May 1, 2006
• Primary Completion (ACTUAL): July 1, 2012
• Study Completion (ACTUAL): July 1, 2012

Study Registration Dates

• First Submitted: January 21, 2014
• First Submitted That Met QC Criteria: January 22, 2014
• First Posted (ESTIMATE): January 23, 2014

Study Record Updates

• Last Update Posted (ACTUAL): March 14, 2018
• Last Update Submitted That Met QC Criteria: March 12, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Keywords: Spinal Cord Injury; Bisphosphonates; Zoledronic acid; Dual Energy X-ray Absorptiometry; Disuse Osteoporosis
• Additional Relevant MeSH Terms: Metabolic Diseases; Central Nervous System Diseases; Nervous System Diseases; Wounds and Injuries; Musculoskeletal Diseases; Trauma, Nervous System; Spinal Cord Diseases; Bone Diseases; Bone Diseases, Metabolic; Osteoporosis; Spinal Cord Injuries; Physiological Effects of Drugs; Bone Density Conservation Agents; Zoledronic Acid
• Other Study ID Numbers: 5481-03-0013; R-454-03 (OTHER: Kessler Foundation Research Center)