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The effect of zoledronic acid on attenuation of bone loss at the hip and knee following acute traumatic spinal cord injury: a randomized-controlled study


Study design

Randomized double blind, placebo-controlled trial.


To examine the effect of early intravenous zoledronic acid (ZA) on bone markers and areal bone mineral density (aBMD) in persons with acute ASIA Impairment Scale (AIS) A traumatic spinal cord injury (SCI).


Two inpatient rehabilitation units.


Thirteen men, 2 women, aged 19–65, C4-T10 AIS A SCI, received 5 mg intravenous ZA vs. placebo 12–21 days post injury. Markers of bone formation (procollagen N-1 terminal propeptide [P1NP]), bone resorption (serum C-telopeptide [CTX]), and aBMD by dual-energy X-ray absorptiometry (DXA) for hip (femur—proximal, intertrochanteric, neck), and knee (distal femur, proximal tibia) were obtained at baseline, 2 weeks post infusion (P1NP, CTX only), 4 and 12 months post injury.


P1NP remained unchanged, while CTX decreased in ZA but increased in controls at 2 weeks (mean difference = −97%, p < 0.01), 4 months (mean difference = −54%, p < 0.05), but not 12 months (mean difference = 3%, p = 0.23). Changes in aBMD at the hip favored ZA at 4 months (mean difference 10.3–14.1%, p < 0.01) and 12 months (mean difference 10.8–13.1%, p < 0.02). At 4 months, changes in aBMD favored ZA at the distal femur (mean difference 6.0%, 95% CI: 0.7–11.2, p < 0.03) but not proximal tibia (mean difference 8.3%, 95% CI: −6.9 to 23.6, p < 0.23). Both groups declined in aBMD at 12 months, with no between group differences.


ZA administered ≤21 days of complete traumatic SCI maintains aBMD at the hip and distal femur at 4 months post injury. This effect is partially maintained at 12 months.

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Fig. 1
Fig. 2

Data availability

All data generated or analyzed during this study are included in this published article and its supplementary information files. Data of individual participants were kept in locked files within the Spinal Cord Injury Center of Thomas Jefferson University. The University retains ownership of these records following study completion


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The authors wish to thank the following individuals for their contribution to this work: Annie S. Kim, BS, Thomas Jefferson University, for assistance with manuscript preparation, table and figure construction. Justin A. Smith, MD, Case Western Reserve University, for assistance with table and figure creation. Marilyn P. Owens, RN, Thomas Jefferson University, for assistance with recruitment, obtaining signed consent forms, blood draws, and follow-up phone calls. Brittany Hayes, BSN, Thomas Jefferson University, for assistance with recruitment, obtaining signed consent forms, data archiving in secured patient files, and follow-up phone calls. Amanda B. Morina, PT, DPT, Thomas Jefferson University, for performing leg length measurements for DXA readings and performing ISNCSCI examinations. Chuan Zhang, Ph.D., University of Georgia, for assistance with image construction and reformatting of supplementary figures.


This research was supported by the U.S. Department of Health & Human Services | ACL | National Institute on Disability, Independent Living, and Rehabilitation Research (NIDILRR) (90SI5012). Cost of brand name Zoledronic acid and all supplies were funded by the grant and purchased through Jefferson pharmacy. Investigators did not shift to generic drugs mid-study, although they became available on study year 3.

Author information




CVO was responsible for project concept and design, pre and post infusion questionnaires, assessing post infusion side effects of participants, and writing the manuscript. RJM was responsible for guiding project construction, assessing study feasibility, and reviewing the written manuscript. CSF was responsible for patient recruitment, study administration, data acquisition, and post infusion evaluation of side effects at the Magee Rehabilitation Hospital. CMM was responsible for interpreting the DXA scans and for creating Fig. S-3. BEL was responsible for randomization method and statistical analysis of results.

Corresponding author

Correspondence to Christina V. Oleson.

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Oleson, C.V., Marino, R.J., Formal, C.S. et al. The effect of zoledronic acid on attenuation of bone loss at the hip and knee following acute traumatic spinal cord injury: a randomized-controlled study. Spinal Cord 58, 921–929 (2020).

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