Zoledronic Acid Treatment After Acute Spinal Cord Injury: Results of a Randomized, Placebo-Controlled Pilot Trial

Abstract

Objective: To determine the effect of intravenous zoledronic acid 5 mg on the extent and course of bone loss after spinal cord injury (SCI).

Design: Double-blind, randomized, placebo-controlled parallel-group trial.

Setting: Acute in-patient, tertiary-care rehabilitation hospital.

Participants: Convenience sample of 17 in-patients with SCI <12 weeks before randomization; American Spinal Injury Association Impairment scale A, B, or C and medically stable. Twelve patients were evaluated at the primary endpoint at 6 months.

Methods: Patients meeting study criteria were randomly assigned to zoledronic acid 5 mg or matching placebo. Dual x-ray absorptiometry scan and serum for bone markers (type 1 procollagen amino-terminal propeptide, bone-specific alkaline phosphatase, collagen type 1 cross-linked C-telopeptide) were obtained at baseline and after 3 months, 6 months, and the every 6 months for up to 2 years.

Main outcome measures: The primary endpoint was change in bone mineral density (BMD) at the total hip after 6 months; secondary endpoints were changes in BMD at other skeletal sites and changes in levels of serum bone markers.

Results: The group treated with zoledronic acid had a smaller decrease in BMD at 6 months at the total hip than the placebo group (right: -2.2 ± 3.4% versus -8.6 ± 3.5%, respectively, P = .03; left: -3.7 ± 1.0% versus -12.3 ± 6.9%, P = .03). Differences in BMD at the femoral neck were similar (right: -5.1 ± 6.5% versus -20.0 ± 6.4%, P = .01; left: -1.1 ± 3.5% versus -11.1 ± 7.4%, P = .02) with larger bone loss and smaller between group differences at the knee. Zoledronic acid resulted in a decrease in serum levels of both formation and resorption markers.

Conclusions: Zoledronic acid is effective at mitigating bone loss after SCI. Duration of efficacy and activity at different skeletal sites may differ from that observed in able-bodied individuals and needs further study.