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Denosumab increases sublesional bone mass in osteoporotic individuals with recent spinal cord injury

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Abstract

Summary

Osteoporosis is a frequent complication related to spinal cord injury (SCI), and data on osteoporosis treatment after SCI is scarce. Treatment with denosumab increases lumbar and femoral BMD and decreases bone turnover markers in individuals with recent SCI. This drug may be a promising therapeutic option in SCI-related osteoporosis.

Introduction

Osteoporosis development is a frequent complication related to SCI, especially at the sublesional level. Nevertheless, data on osteoporosis treatment after SCI is scarce, particularly short term after injury, when the highest bone loss is produced. The aim of this study was to analyze the efficacy of denosumab in the treatment of SCI-related osteoporosis.

Methods

Fourteen individuals aged 39 ± 15 years with osteoporosis secondary to recent SCI (mean injury duration 15 ± 4 months) were treated with denosumab for 12 months. Bone turnover markers (BTMs) (PINP, bone ALP, sCTx), 25-hydroxyvitamin D (25OHD) levels and bone mineral density (BMD) at the lumbar spine (LS), total hip (TH), and femoral neck (FN) were assessed at baseline and at 12 months. All participants received calcium and vitamin D supplementation.

Results

At 12 months, SCI denosumab-treated participants showed a significant increase in BMD at TH (+2.4 ± 3.6 %, p = 0.042), FN (+3 ± 3.6 %, p = 0.006), and LS (+7.8 ± 3.7 %, p < 0.001) compared to baseline values. Denosumab treatment was associated with significant decreases in BTMs (bone ALP −42 %, p < 0.001; PINP −58 %, p < 0.001, sCTx −57 %, p = 0.002) at 12 months. BMD evolution was not related to BTM changes or 25OHD serum levels. No skeletal fractures or serious adverse events were observed during follow-up.

Conclusions

Treatment with denosumab increases lumbar and femoral BMD and decreases bone turnover markers in individuals with recent SCI. This drug may be a promising therapeutic option in SCI-related osteoporosis.

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Fig. 1

Abbreviations

SCI:

Spinal cord injury

i.v.:

Intravenous

25OHD:

25-Hydroxyvitamin D

BMD:

Bone mineral density

BTMs:

Bone turnover markers

BMI:

Body mass index

ASIA:

American Spinal Cord Injury Association

Bone ALP:

Bone alkaline phosphatase

PINP:

Propeptide amino-terminal of type I procollagen

sCTx:

Serum carboxy-terminal telopeptide of type I collagen

p :

p value

SD:

Standard deviation

References

  1. Gifre L, Vidal J, Carrasco J, Filella X, Ruiz-Gaspà S, Muxi A, Portell E, Monegal A, Guañabens N, Peris P (2015) Effect of recent spinal cord injury on Wnt signaling antagonists (sclerostin and Dkk-1) and their relationship with bone loss. A 12-month prospective study. J Bone Miner Res 30:1014–1021

    Article  PubMed  CAS  Google Scholar 

  2. Gifre L, Vidal J, Carrasco J, Portell E, Puig J, Monegal A, Guañabens N, Peris P (2014) Incidence of skeletal fractures after traumatic spinal cord injury: a 10-year follow-up study. Clin Rehabil 28:361–369

    Article  PubMed  Google Scholar 

  3. Frey-Rindova P, de Bruin ED, Stüssi E, Dambacher MA, Dietz V (2000) Bone mineral density in upper and lower extremities during 12 months after spinal cord injury measured by peripheral quantitative computed tomography. Spinal Cord 38:26–32

    Article  PubMed  CAS  Google Scholar 

  4. Shojaei H, Soroush MR, Modirian E (2006) Spinal cord injury-induced osteoporosis in veterans. J Spinal Disord Tech 19:114–117

    Article  PubMed  Google Scholar 

  5. Bryson JE, Gourlay ML (2009) Bisphosphonate use in acute and chronic spinal cord injury: a systematic review. J Spinal Cord Med 32:215–225

    PubMed  PubMed Central  Google Scholar 

  6. Chang KV, Hung CY, Chen WS, Lai MS, Chien KL, Han DS (2013) Effectiveness of bisphosphonate analogues and functional electrical stimulation on attenuating post-injury osteoporosis in spinal cord injury patients—a systematic review and meta-analysis. PLoS One 8, e81124

    Article  PubMed  PubMed Central  Google Scholar 

  7. Bauman WA, Cirnigliaro CM, La Fountaine MF, Martinez L, Kirshblum SC, Spungen AM (2015) Zoledronic acid administration failed to prevent bone loss at the knee in persons with acute spinal cord injury: an observational cohort study. J Bone Miner Metab 33:410–421

    Article  PubMed  CAS  Google Scholar 

  8. Gordon KE, Wald MJ, Schnitzer TJ (2013) Effect of parathyroid hormone combined with gait training on bone density and bone architecture in people with chronic spinal cord injury. PM R 5:663–671

    Article  PubMed  Google Scholar 

  9. Cummings SR, San Martin J, McClung MR, Siris ES, Eastell R, Reid IR, Delmas P, Zoog HB, Austin M, Wang A, Kutilek S, Adami S, Zanchetta J, Libanati C, Siddhanti S, Christiansen C, Trial FREEDOM (2009) Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med 361:756–765

    Article  PubMed  CAS  Google Scholar 

  10. McClung MR, Lewiecki EM, Cohen SB, Bolognese MA, Woodson GC, Moffett AH, Peacock M, Miller PD, Lederman SN, Chesnut CH, Lain D, Kivitz AJ, Holloway DL, Zhang C, Peterson MC, Bekker PJ, AMG 162 Bone Loss Study Group (2006) Denosumab in postmenopausal women with low bone mineral density. N Engl J Med 354:821–831

    Article  PubMed  CAS  Google Scholar 

  11. Jiang SD, Jiang LS, Dai LY (2007) Effects of spinal cord injury on osteoblastogenesis, osteoclastogenesis and gene expression profiling in osteoblasts in young rats. Osteoporos Int 18:339–349

    Article  PubMed  CAS  Google Scholar 

  12. Waring WP 3rd, Biering-Sorensen F, Burns S, Donovan W, Graves D, Jha A, Jones L, Kirshblum S, Marino R, Mulcahey MJ, Reeves R, Scelza WM, Schmidt-Read M, Stein A (2010) 2009 review and revisions of the international standards for the neurological classification of spinal cord injury. J Spinal Cord Med 33:346–352

    PubMed  PubMed Central  Google Scholar 

  13. (1994) Assessment of fracture risk and its application to screening for postmenopausal osteoporosis. Report of a WHO Study Group. World Health Organ Tech Rep Ser 843:1-129

  14. Ominsky MS, Libanati C, Niu QT, Boyce RW, Kostenuik PJ, Wagman RB, Baron R, Dempster DW (2015) Sustained modeling-based bone formation during adulthood in cynomolgus monkeys may contribute to continuous BMD gains with denosumab. J Bone Miner Res 30:1280–1289

    Article  PubMed  CAS  Google Scholar 

  15. Giangregorio L, McCartney N (2006) Bone loss and muscle atrophy in spinal cord injury: epidemiology, fracture prediction, and rehabilitation strategies. J Spinal Cord Med 29:489–500

    PubMed  PubMed Central  Google Scholar 

  16. Jiang SD, Dai LY, Jiang LS (2006) Osteoporosis after spinal cord injury. Osteoporos Int 17:180–192

    Article  PubMed  Google Scholar 

  17. Orwoll E, Teglbjærg CS, Langdahl BL, Chapurlat R, Czerwinski E, Kendler DL, Reginster JY, Kivitz A, Lewiecki EM, Miller PD, Bolognese MA, McClung MR, Bone HG, Ljunggren Ö, Abrahamsen B, Gruntmanis U, Yang YC, Wagman RB, Siddhanti S, Grauer A, Hall JW, Boonen S (2012) A randomized, placebo-controlled study of the effects of denosumab for the treatment of men with low bone mineral density. J Clin Endocrinol Metab 97:3161–3169

    Article  PubMed  CAS  Google Scholar 

  18. Stopeck AT, Lipton A, Body JJ, Steger GG, Tonkin K, de Boer RH, Lichinitser M, Fujiwara Y, Yardley DA, Viniegra M, Fan M, Jiang Q, Dansey R, Jun S, Braun A (2010) Denosumab compared with zoledronic acid for the treatment of bone metastases in patients with advanced breast cancer: a randomized, double-blind study. J Clin Oncol 28:5132–5139

    Article  PubMed  CAS  Google Scholar 

  19. Adriaansen JJ, Post MW, de Groot S, van Asbeck FW, Stolwijk-Swüste JM, Tepper M, Lindeman E (2013) Secondary health conditions in persons with spinal cord injury: a longitudinal study from one to five years post-discharge. J Rehabil Med 45:1016–1022

    Article  PubMed  Google Scholar 

  20. Noreau L, Proulx P, Gagnon L, Drolet M, Laramée MT (2000) Secondary impairments after spinal cord injury: a population-based study. Am J Phys Med Rehabil 79:526–535

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This work was funded by the Fundació La Marató de TV3.

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Corresponding author

Correspondence to L. Gifre.

Ethics declarations

The procedures followed were in accordance with the Ethical Standards of the Helsinki Declaration.

Funding

This work was funded by a grant from Fundació La Marató de TV3.

Conflicts of interest

None.

Ethics approval

Ethical approval was obtained from the Hospital Clinic of Barcelona and from the Neurorehabilitation Guttmann Institute Ethics Committees. 

Consent to participate

All participants provided written informed consent prior to the initiation of this study. 

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Gifre, L., Vidal, J., Carrasco, J.L. et al. Denosumab increases sublesional bone mass in osteoporotic individuals with recent spinal cord injury. Osteoporos Int 27, 405–410 (2016). https://doi.org/10.1007/s00198-015-3333-5

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  • DOI: https://doi.org/10.1007/s00198-015-3333-5

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