Osteoporosis International

, Volume 22, Issue 1, pp 271–279

Early treatment with zoledronic acid prevents bone loss at the hip following acute spinal cord injury

  • J. S. Bubbear
  • A. Gall
  • F. R. I. Middleton
  • M. Ferguson-Pell
  • R. Swaminathan
  • R. W. Keen
Original Article

Abstract

Summary

Osteoporosis after spinal cord injury is common. Reductions in bone density are rapid and fracture rates are higher after injury. Early treatment with 4 mg zoledronic acid significantly reduced bone loss at the hip compared to untreated individuals in the first year. Treatment appeared safe and well tolerated.

Introduction

Bone mineral density (BMD) is lost rapidly following spinal cord injury (SCI), predominantly in the lower limbs. Bone turnover markers suggest an early increase in resorption.

Methods

A randomised, open-label study of 14 patients with acute SCI randomised to receive 4 mg IV zoledronic acid or standard treatment. BMD was measured by dual-X-ray absorptiometry at the lumbar spine and hip (femoral neck, total and trochanter) at baseline, 3, 6 and 12 months. Bone turnover markers (serum C-terminal telopeptide and Procollagen I N-terminal peptide and urinary N-terminal telopeptide/Cr ratio) were also measured.

Results

After 12 months, there was a significant difference in BMD between the groups at the total hip (12.4%, p = 0.005), trochanter (13.4%, p = 0.028) and lumbar spine (2.7%, p = 0.033). However, the difference between groups at the femoral neck was not significant (4.8%, p = 0.741). In the treated group, bone resorption was reduced and remained reduced up to 12 months. Other than flu-like symptoms immediately after the infusion, no adverse events were observed.

Conclusion

IV zoledronic acid is an effective and well-tolerated treatment to prevent bone mineral density loss at the total hip and trochanter for up to 12 months following SCI.

Keywords

Bisphosphonate Osteoporosis Spinal cord injury Zoledronic acid 

References

  1. 1.
    Biering-Sorensen F, Bohr HH, Schaadt OP (1990) Longitudinal study of bone mineral content in the lumbar spine, the forearm and the lower extremities after spinal cord injury. Eur J Clin Invest 20:330–335CrossRefPubMedGoogle Scholar
  2. 2.
    Nottage WM (1981) A review of long-bone fractures in patients with spinal cord injuries. Clin Orthop Relat Res 155:65–70PubMedGoogle Scholar
  3. 3.
    Vestergaard P, Krogh K, Rejnmark L, Mosekilde L (1998) Fracture rates and risk factors for fractures in patients with spinal cord injury. Spinal Cord 36:790–796CrossRefPubMedGoogle Scholar
  4. 4.
    Pietschmann P, Pils P, Woloszczuk W, Maerk R, Lessan D, Stipicic J (1992) Increased serum osteocalcin levels in patients with paraplegia. Paraplegia 30:204–209PubMedGoogle Scholar
  5. 5.
    Roberts D, Lee W, Cuneo RC, Wittmann J, Ward G, Flatman R, McWhinney B, Hickman PE (1998) Longitudinal study of bone turnover after acute spinal cord injury. J Clin Endocrinol Metab 83:415–422CrossRefPubMedGoogle Scholar
  6. 6.
    Maimoun L, Couret I, Micallef JP, Peruchon E, Mariano-Goulart D, Rossi M, Leroux JL, Ohanna F (2002) Use of bone biochemical markers with dual-energy X-ray absorptiometry for early determination of bone loss in persons with spinal cord injury. Metabolism 51:958–963CrossRefPubMedGoogle Scholar
  7. 7.
    Chappard D, Minaire P, Privat C, Berard E, Mendoza-Sarmiento J, Tournebise H, Basle MF, Audran M, Rebel A, Picot C (1995) Effects of tiludronate on bone loss in paraplegic patients. J Bone Miner Res 10:112–118CrossRefPubMedGoogle Scholar
  8. 8.
    Zehnder Y, Risi S, Michel D, Knecht H, Perrelet R, Kraenzlin M, Zach GA, Lippuner K (2004) Prevention of bone loss in paraplegics over 2 years with alendronate. J Bone Miner Res 19:1067–1074CrossRefPubMedGoogle Scholar
  9. 9.
    Pearson EG, Nance PW, Leslie WD, Ludwig S (1997) Cyclical etidronate: its effect on bone density in patients with acute spinal cord injury. Arch Phys Med Rehabil 78:269–272CrossRefPubMedGoogle Scholar
  10. 10.
    Nance PW, Schryvers O, Leslie W, Ludwig S, Krahn J, Uebelhart D (1999) Intravenous pamidronate attenuates bone density loss after acute spinal cord injury. Arch Phys Med Rehabil 80:243–251CrossRefPubMedGoogle Scholar
  11. 11.
    Green JR, Muller K, Jaeggi KA (1994) Preclinical pharmacology of CGP 42′446, a new, potent, heterocyclic bisphosphonate compound. J Bone Miner Res 9:745–751CrossRefPubMedGoogle Scholar
  12. 12.
    Reid IR, Brown JP, Burckhardt P, Horowitz Z, Richardson P, Trechsel U, Widmer A, Devogelaer JP, Kaufman JM, Jaeger P, Body JJ, Brandi ML, Broell J, Di Micco R, Genazzani AR, Felsenberg D, Happ J, Hooper MJ, Ittner J, Leb G, Mallmin H, Murray T, Ortolani S, Rubinacci A, Saaf M, Samsioe G, Verbruggen L, Meunier PJ (2002) Intravenous zoledronic acid in postmenopausal women with low bone mineral density. N Engl J Med 346:653–661CrossRefPubMedGoogle Scholar
  13. 13.
    Black DM, Delmas PD, Eastell R, Reid IR, Boonen S, Cauley JA, Cosman F, Lakatos P, Leung PC, Man Z, Mautalen C, Mesenbrink P, Hu H, Caminis J, Tong K, Rosario-Jansen T, Krasnow J, Hue TF, Sellmeyer D, Eriksen EF, Cummings SR (2007) Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis. N Engl J Med 356:1809–1822CrossRefPubMedGoogle Scholar
  14. 14.
    Hosking D, Lyles K, Brown JP, Fraser WD, Miller P, Curiel MD, Devogelaer JP, Hooper M, Su G, Zelenakas K, Pak J, Fashola T, Saidi Y, Eriksen EF, Reid IR (2007) Long-term control of bone turnover in Paget’s disease with zoledronic acid and risedronate. J Bone Miner Res 22:142–148CrossRefPubMedGoogle Scholar
  15. 15.
    Wood DE, Dunkerley AL, Tromans AM (2001) Results from bone mineral density scans in twenty-two complete lesion paraplegics. Spinal Cord 39:145–148CrossRefPubMedGoogle Scholar
  16. 16.
    Dauty M, Perrouin VB, Maugars Y, Dubois C, Mathe JF (2000) Supralesional and sublesional bone mineral density in spinal cord-injured patients. Bone 27:305–309CrossRefPubMedGoogle Scholar
  17. 17.
    Demirel G, Yilmaz H, Paker N, Onel S (1998) Osteoporosis after spinal cord injury. Spinal Cord 36:822–825CrossRefPubMedGoogle Scholar
  18. 18.
    Gilchrist NL, Frampton CM, Acland RH, Nicholls MG, March RL, Maguire P, Heard A, Reilly P, Marshall K (2007) Alendronate prevents bone loss in patients with acute spinal cord injury: a randomized, double-blind, placebo-controlled study. J Clin Endocrinol Metab 92:1385–1390CrossRefPubMedGoogle Scholar
  19. 19.
    Cranney A, Wells G, Willan A, Griffith L, Zytaruk N, Robinson V, Black D, Adachi J, Shea B, Tugwell P, Guyatt G (2002) Meta-analyses of therapies for postmenopausal osteoporosis. II. Meta-analysis of alendronate for the treatment of postmenopausal women. Endocr Rev 23:508–516CrossRefPubMedGoogle Scholar
  20. 20.
    Bjarnason NH, Henriksen EE, Alexandersen P, Christgau S, Henriksen DB, Christiansen C (2002) Mechanism of circadian variation in bone resorption. Bone 30:307–313CrossRefPubMedGoogle Scholar
  21. 21.
    Hannon R, Eastell R (2000) Preanalytical variability of biochemical markers of bone turnover. Osteoporos Int 11(Suppl 6):S30–S44CrossRefPubMedGoogle Scholar
  22. 22.
    Clowes JA, Hannon RA, Yap TS, Hoyle NR, Blumsohn A, Eastell R (2002) Effect of feeding on bone turnover markers and its impact on biological variability of measurements. Bone 30:886–890CrossRefPubMedGoogle Scholar
  23. 23.
    Scariano JK, Garry PJ, Montoya GD, Wilson JM, Baumgartner RN (2001) Critical differences in the serial measurement of three biochemical markers of bone turnover in the sera of pre- and postmenopausal women. Clin Biochem 34:639–644CrossRefPubMedGoogle Scholar

Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2010

Authors and Affiliations

  • J. S. Bubbear
    • 1
  • A. Gall
    • 2
  • F. R. I. Middleton
    • 2
  • M. Ferguson-Pell
    • 3
  • R. Swaminathan
    • 4
  • R. W. Keen
    • 1
    • 5
  1. 1.Metabolic UnitRoyal National Orthopaedic HospitalStanmoreUK
  2. 2.Spinal Cord Injuries CentreRoyal National Orthopaedic HospitalStanmore, MiddlesexUK
  3. 3.Faculty of Rehabilitation MedicineUniversity of AlbertaEdmontonCanada
  4. 4.Department of Chemical PathologySt Thomas’s HospitalLondonUK
  5. 5.Institute of Orthopaedic and Musculoskeletal ScienceUniversity College HospitalLondonUK

Personalised recommendations