Prevention of Bone Loss after Acute SCI by Zoledronic Acid: Durability, Effect on Bone Strength and Use of Biomarkers to Guide Therapy

Project: Research project

Description

LAY ABSTRCT

Background/Rationale: Immediately after people experience acute spinal cord injury (SCI), there is a rapid and profound loss of bone, primarily in the lower extremities, due to the loss of normal weight-bearing that occurs with walking. This bone loss does not result in any symptoms but is important because of the concern for fracture with re-introduction of rehabilitation-based weight-bearing in the months immediately after SCI as well as leading to the well-demonstrated high risk of fractures some years later. These fractures occur primarily in the area around the knee, the skeletal area where bone loss is greatest, and have significant impact on quality of life, physical function and healthcare expenditures. Drugs are currently available to treat osteoporosis, a natural condition of bone loss that occurs primarily with aging, and these same drugs work by blocking processes responsible for bone loss after acute SCI. Studies with these drugs in people after acute SCI have suggested that these drugs would be of benefit, but many questions still remain to be answered such as when to start treatment after acute SCI, how long to treat someone, and how long the treatment effect will last. Because of these unknowns, bone-specific interventions are not considered after acute SCI; indeed, the current standard of care for people who have had an acute SCI does not include treatments to prevent bone loss.

Objectives: The goal of this research study is to define the best approach to the treatment of bone loss after acute SCI, focusing on zoledronic acid, a potent drug that can be given once-yearly as an intravenous infusion and which is currently used to treat osteoporosis. The effect of the drug on the skeleton will be assessed, with particular attention to loss of not only bone mass but also bone strength at the hips and knees. The value of repeat treatment after one year and the effect of delaying treatment will also both be defined. In addition, this study will evaluate the value of using blood tests to identify when it would be best to consider retreatment.

Study Procedures: The research study proposed is a clinical trial of 2 years’ duration, enrolling people in the first months after their acute SCI. Participants would be assigned to receive zoledronic acid or placebo, with assignment being done is a scientifically sound manner. After the first year, half the study participants would continue on their initial study medication assignment and half would switch to the opposite treatment. At regular intervals during the 2 years, the effects of the study treatment would be monitored by obtaining DXA and CT bone studies as well as getting a blood sample. Safety would also be monitored throughout the study.

Outcomes: This study will define for people with acute SCI (1) if a single infusion of zoledronic acid is effective at preventing loss of bone and bone strength and for how long; (2) if retreatment with zoledronic acid at one year will result in better efficacy than only a single treatment shortly after SCI; (3) whether immediate treatment (within 4 months of acute SCI) produces better results than waiting until later to treat, and (4) how serum markers of bone metabolism can be used to guide treatment decisions of when to treat. It is anticipated that the demonstration of the effectiveness of this simple once-yearly intervention will result in a change in the standard of care for all people who suffer an acute SCI, such that treatment will be initiated while they are still in the acute-care reha
StatusFinished
Effective start/end date9/30/149/29/19

Funding

  • U.S. Army Medical Research and Materiel Command (W81XWH-14-2-0193)

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zoledronic acid
Spinal Cord Injuries
Biomarkers
Bone and Bones
Therapeutics
Pharmaceutical Preparations
Retreatment
Weight-Bearing
Standard of Care
Osteoporosis
Knee