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

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 additio