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Effect of recent spinal cord injury on the OPG/RANKL system and its relationship with bone loss and the response to denosumab therapy

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Abstract

Summary

There is marked bone loss after spinal cord injury (SCI); however, its pathogenesis and clinical management remain unclear. The increased circulating levels of receptor activator of nuclear factor kB ligand (RANKL) associated with bone loss shortly after SCI and the prevention of bone loss with denosumab treatment suggest a contributory role of RANKL in SCI-induced osteoporosis.

Introduction

Bone turnover and bone loss are markedly increased shortly after SCI. However, the pathogenesis and clinical management of this process remain unclear, especially the role of the osteoprotegerin (OPG)/RANKL system in this disorder. The aim of this study was to analyze serum levels of OPG and RANKL in bone loss associated with recent SCI and the effect of denosumab treatment on these mediators.

Methods

Twenty-three males with recent complete SCI were prospectively included. Serum OPG and RANKL levels, bone turnover markers (PINP, bone ALP, CTX), and bone mineral density (BMD) were assessed at baseline, at 6 months of follow-up, prior to initiating denosumab, and 6 months after treatment. The results were compared with a healthy control group.

Results

At baseline, SCI patients showed higher RANKL levels vs. controls which were correlated with days-since-SCI and total hip BMD loss at 6 months. OPG levels were similar to controls at baseline. After denosumab treatment, OPG showed no changes, whereas RANKL levels became undetectable in 67% of patients. Patients with undetectable RANKL during treatment showed better response in femoral BMD and bone markers vs. patients with detectable RANKL at 6 months of denosumab. Increased parathormone (PTH) levels during treatment were negatively correlated with RANKL changes.

Conclusions

RANKL levels are increased after SCI and related to BMD loss at the proximal femur, becoming undetectable after denosumab treatment. The effect of denosumab on preventing sublesional bone loss, especially in patients with undetectable levels during treatment, suggests a contributory role of RANKL in this process.

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Abbreviations

SCI:

Spinal cord injury

RANKL:

Receptor activator of nuclear factor kB ligand

OPG:

Osteoprotegerin

BMD:

Bone mineral density

25OHD:

25 hydroxyvitamin D

BMI:

Body mass index

AIS:

ASIA Impairment Scale

PTH:

Parathormone

Bone ALP:

Bone alkaline phosphatase

PINP:

Propeptide amino-terminal of type I procollagen

CTX:

Serum carboxy-terminal telopeptide of type I collagen

SD:

Standard deviation

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Acknowledgments

This work was funded by grants from Fundación Española de Investigación Ósea y Metabolismo Mineral (FEIOMM) and Fundació La Marató de TV3.

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Author notes

  1. L. Gifre

    Present address: Rheumatology Department, Hospital Universitari Germans Trias i Pujol, Badalona, Spain

Authors and Affiliations

  1. Rheumatology Department, Hospital Clinic of Barcelona, University of Barcelona, Barcelona, Spain

    L. Gifre, A. Monegal, N. Guañabens & P. Peris

  2. CIBERehd, Barcelona, Spain

    S. Ruiz-Gaspà, N. Guañabens & P. Peris

  3. Public Health Department, University of Barcelona, Barcelona, Spain

    J. L. Carrasco

  4. Guttmann Neurorehabilitation Institute, Universitat Autònoma de Barcelona, Badalona, Spain

    E. Portell & J. Vidal

  5. Nuclear Medicine Department, Hospital Clínic of Barcelona, Barcelona, Spain

    A. Muxi

  6. Metabolic Bone Diseases Unit, Department of Rheumatology, Hospital Clinic of Barcelona, Villarroel 170, 08036, Barcelona, Spain

    P. Peris

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  1. L. Gifre
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Correspondence to P. Peris.

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Gifre, L., Ruiz-Gaspà, S., Carrasco, J.L. et al. Effect of recent spinal cord injury on the OPG/RANKL system and its relationship with bone loss and the response to denosumab therapy. Osteoporos Int 28, 2707–2715 (2017). https://doi.org/10.1007/s00198-017-4090-4

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  • DOI: https://doi.org/10.1007/s00198-017-4090-4

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