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Loss of lower extremity bone mineral density 1 year after denosumab is discontinued in persons with subacute spinal cord injury

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Abstract

Summary

Twelve months following discontinuation of denosumab, the percent decrease in mean bone mineral density (BMD) values at the hip and knee regions were similar between both the denosumab and placebo groups. These findings emphasize the need for additional trials to understand the effect of continued administration of denosumab after subacute spinal cord injury (SCI) to avoid this demineralization.

Objective

To determine changes in BMD 1 year after denosumab was discontinued in participants with subacute SCI who had drug treatment initiated within 90 days post SCI and continued for 1 year.

Methods

Fourteen participants who completed a randomized, double-blinded, placebo-controlled drug trial (parent study: denosumab 60 mg (Prolia, Amgen Inc., n = 8) or placebo (n = 6); administered at baseline, 6, and 12 months) were followed 12 months after the 18 months from baseline primary end point was completed. The BMD of skeletal regions below the SCI at higher risk of fracture was measured [total hip, distal femur epiphysis (DFE), distal femur metaphysis (DFM), and proximal tibia epiphysis (PTE)] by dual energy X-ray absorptiometry.

Results

The percent decreases in mean BMD values at all regions of the hip and knee from 18 to 30 months were similar in both the denosumab and placebo groups. However, at 30 months, the absolute values for mean BMD remained significantly higher in the drug treatment than that of the placebo group at the DFM (p = 0.03), DFE (p = 0.04), and PTE (p = 0.05).

Conclusions

In persons with SCI who initiated denosumab treatment during the subacute injury phase and maintained treatment for 1 year, the discontinuation of drug resulted in percent loss of mean BMD similar to that of the placebo group, with absolute mean BMD values at the knee regions at the 12-month follow-up visit significantly higher in the drug treatment than those in the placebo group. These data underscore the need to study continued administration of denosumab after subacute SCI to avoid marked demineralization in the sublesional skeleton upon discontinuation of this agent.

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Acknowledgements

The authors wish to thank the James J. Peters VA Medical Center, Bronx, NY, the Department of Veterans Affairs Rehabilitation Research and Development Service, the Kessler Institute for Rehabilitation, and the Kessler Foundation, West Orange, NJ, for their support. The authors would also like to thank Dr. Christopher P. Cardozo for his suggestions with the final version of this manuscript.

Funding

This research was supported by Craig H. Neilson Foundation (#297267) and the VA Rehabilitation Research and Development Service’s National Center for the Medical Consequences of Spinal Cord Injury (#B9212-C, #B2020-C).

Author information

Authors and Affiliations

  1. Department of Veterans Affairs Rehabilitation Research and Development Service National Center for the Medical Consequences of Spinal Cord Injury, James J. Peters Veterans Affairs Medical Center, 130 West Kingsbridge Road, Bronx, NY, 10468, USA

    Christopher M. Cirnigliaro & Michael F. La Fountaine

  2. Department of Physical Therapy, School of Health and Medical Sciences, Seton Hall University, South Orange, NJ, USA

    Michael F. La Fountaine

  3. Departments of Medical Sciences and Neurology, Hackensack Meridian School of Medicine, Nutley, NJ, USA

    Michael F. La Fountaine

  4. Department of Interdisciplinary Studies, School of Health Professions, Rutgers Biomedical and Health Sciences, Newark, NJ, USA

    J. Scott Parrott

  5. Kessler Institute for Rehabilitation, West Orange, NJ, USA

    Steven C. Kirshblum & Susan J. Sauer

  6. Kessler Foundation Research Center, West Orange, NJ, USA

    Steven C. Kirshblum

  7. Department of Physical Medicine and Rehabilitation, Rutgers New Jersey Medical School, Newark, NJ, USA

    Steven C. Kirshblum

  8. Department of Nutritional Sciences, Rutgers University, New Brunswick, NJ, USA

    Sue A. Shapses

  9. Department of Medicine, Rutgers-Robert Wood Johnson Medical School, NJ, New Brunswick, USA

    Sue A. Shapses

  10. DP Clinical, Inc, Rockville, MD, USA

    Isa A. McClure

  11. Departments of Medicine and Rehabilitation and Human Performance, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    William A. Bauman

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  1. Christopher M. Cirnigliaro
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  2. Michael F. La Fountaine
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  5. Susan J. Sauer
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  7. Isa A. McClure
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  8. William A. Bauman
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Corresponding author

Correspondence to Christopher M. Cirnigliaro.

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Conflict of interest

Christopher M. Cirnigliaro, Michael F. La Fountaine, J. Scott Parrott, Steven C. Kirshblum, Susan J. Sauer, Sue A. Shapses, Isa A. McClure, and William A. Bauman declare that they have no conflicts of interest to report

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Cirnigliaro, C.M., La Fountaine, M.F., Parrott, J.S. et al. Loss of lower extremity bone mineral density 1 year after denosumab is discontinued in persons with subacute spinal cord injury. Osteoporos Int 34, 741–748 (2023). https://doi.org/10.1007/s00198-023-06679-w

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  • DOI: https://doi.org/10.1007/s00198-023-06679-w

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