Calcified Tissue International

, Volume 80, Issue 5, pp 316–322 | Cite as

Treatment with Zoledronic Acid Ameliorates Negative Geometric Changes in the Proximal Femur following Acute Spinal Cord Injury

  • J. Shapiro
  • B. Smith
  • T. Beck
  • P. Ballard
  • M. Dapthary
  • K. BrintzenhofeSzoc
  • J. Caminis


Acute spinal cord injury is associated with rapid bone loss and an increased risk of fracture. In this double-blind, randomized, placebo-controlled trial, 17 patients were followed for 1 year after administration of either 4 or 5 mg of zoledronic acid or placebo. Bone mineral density (BMD) and structural analyses of the proximal femur were performed using the hip structural analysis program at entry, 6 months, and 12 months. The 17 subjects completed 12 months of observation, nine receiving placebo and eight zoledronic acid. The placebo group showed a decrease in BMD, cross-sectional area, and section modulus and an increase in buckling ratio at each proximal femur site at 6 and 12 months. Six months after zoledronic acid, BMD, cross-sectional area, and section modulus increased at the femoral neck and intertrochanteric regions and buckling ratio decreased consistent with improved bone stability. However, at 12 months, the femoral narrow-neck values declined to baseline. In contrast to placebo, the intertrochanteric region and femur shaft were maintained at or near baseline through 12 months in the zoledronic acid-treated group. Urine N-telopeptide excretion was increased at baseline and declined in both the placebo and treatment groups during the 12 months of observation. We conclude that a single administration of zoledronic acid will ameliorate bone loss and maintain parameters of bone strength at the three proximal femur sites for 6 months and at the femur intertrochanteric and shaft sites for 12 months.


Bone loss Spinal cord injury Zoledronic acid Dual-energy X-ray absorptiometry Hip structural analysis 



We thank Dr. Peter Richardson, Head of Development at Novartis Pharmaceuticals, Japan, for his assistance in the initiation of the study and Dr. Uri Liberman, University of Tel Aviv, for editorial assistance. Funding for this work was provided by the National Space Biomedical Research Institute and Novartis Pharmaceuticals, Inc.


  1. 1.
    LaPlante MP (1988) Data on Disability from the National Health Interview Survey 1983–1985. US National Institute on Disability and Rehabilitation Research, Washington DCGoogle Scholar
  2. 2.
    Kirshblum SC, Groah SL, McKinley WO, Gittler MS, Stiens SA (2002) Spinal cord injury medicine: etiology, classification, and acute medical management. Arch Phys Med Rehabil 83(suppl 1):S50–S57, S90–S98PubMedCrossRefGoogle Scholar
  3. 3.
    Lazo MG, Shirazi P, Sam M, Giobbie-Hurder A, Blacconiere MJ, Muppidi M (2001) Osteoporosis and risk of fracture in men with spinal cord injury. Spinal Cord 39:208–214PubMedCrossRefGoogle Scholar
  4. 4.
    Dauty M, Perrouin Verbe B, Maugars Y, Dubois C, Mathe JF (2000) Supralesional and sublesional bone mineral density in spinal cord-injured patients. Bone 27:305–309PubMedCrossRefGoogle Scholar
  5. 5.
    Chen Y, DeVivo MJ, Stover SL, Lloyd LK (2002) Recurrent kidney stone: a 25-year follow-up study in persons with spinal cord injury. Urology 60:228–232PubMedCrossRefGoogle Scholar
  6. 6.
    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 78:269–272PubMedCrossRefGoogle Scholar
  7. 7.
    Minaire P, Berard E, Meunier PJ, Edouard C, Goedert G, Pilonchery G (1981) Effects of disodium dichloromethylene diphosphonate on bone loss in paraplegic patients. J Clin Invest 68:1086–1092PubMedCrossRefGoogle Scholar
  8. 8.
    Minaire P, Depassio J, Berard E, Meunier PJ, Edouard C, Pilonchery G, Goedert G (1987) Effects of clodronate on immobilization bone loss. Bone 8(suppl 1):S63–S68PubMedGoogle Scholar
  9. 9.
    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 10:112–118PubMedCrossRefGoogle Scholar
  10. 10.
    Sniger W, Garshick E (2002) Alendronate increases bone density in chronic spinal cord injury: a case report. Arch Phys Med Rehabil 83:139–140PubMedCrossRefGoogle Scholar
  11. 11.
    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 80:243–251PubMedCrossRefGoogle Scholar
  12. 12.
    American Spinal Injury Association, International Medical Society of Paraplegia (2000) International Standards for Neurological Classification of Spinal Cord Injury, rev, 5th ed. Barcelona, Sept. 7, 1992Google Scholar
  13. 13.
    Damiano DL, Quinlivan JM, Owen BF, Payne P, Nelson KC, Abel MF (2002) What does the Ashworth scale really measure and are instrumented measures more valid and precise? Dev Med Child Neurol 4:112–118CrossRefGoogle Scholar
  14. 13a.
    Physicians’ Desk Reference, 58th ed. (2004) Thomson Healthcare, Thomson PDR, Montvale, NJGoogle Scholar
  15. 14.
    Boudousq V, Goulart DM, Dinten JM, de Kerleau CC, Thomas E, Mares O, Kotski PO (2005) Image resolution and magnification using a cone beam densitometer: optimizing data acquisition for hip morphometric analysis. Osteoporos Int 16:813–822PubMedCrossRefGoogle Scholar
  16. 15.
    Beck TJ, Looker AC, Ruff CB, Sievanen H, Wahner HW (2000) Structural trends in the aging femoral neck and proximal shaft: analysis of the Third National Health and Nutrition Examination Survey dual-energy X-ray absorptiometry data. J Bone Miner Res 15:297–204CrossRefGoogle Scholar
  17. 16.
    Martin RB, Burr DB (1984) Non-invasive measurement of long bone cross-sectional moment of inertia by photon absorptiometry. J Biomech 17:195–201PubMedCrossRefGoogle Scholar
  18. 17.
    Burr DB (1997) Muscle strength, bone mass and age-related bone loss. J Bone Miner Res 12:1547–1551PubMedCrossRefGoogle Scholar
  19. 18.
    Kaptoge S, Dalzell N, Jakes RW, Wareham N, Day NE, Khaw KT, Beck TJ, Loveridge N, Reeve J (2003) Hip section modulus, a measure of bending resistance, is more strongly related to reported physical activity than BMD. Osteoporos Int 4:941–949CrossRefGoogle Scholar
  20. 19.
    Melton LJ 3rd, Beck TJ, Amin S, Khosla S, Achenbach SJ, Oberg AL, Riggs BL (2005) Contributions of bone density and structure to fracture risk assessment in men and women. Osteoporos Int 16:460–467PubMedCrossRefGoogle Scholar
  21. 20.
    Looker AC, Beck TJ (2004) Maternal history of osteoporosis and femur geometry. Calcif Tissue Int 75:277–285PubMedCrossRefGoogle Scholar
  22. 21.
    Body JJ, Diel I, Bell R (2004) Profiling the safety and tolerability of bisphosphonates. Semin Oncol 31(suppl 10):73–78PubMedCrossRefGoogle Scholar
  23. 22.
    Berenson J, Hirschberg R (2004) Safety and convenience of a 15-minute infusion of zoledronic acid. Oncologist 9:319–329PubMedCrossRefGoogle Scholar
  24. 23.
    Mechanick JI, Pomerantz F, Flanagan S, Stein A, Gordon WA, Ragnarsson KT (1997) Parathyroid hormone suppression in spinal cord injury patients is associated with the degree of neurological impairment and not the level of injury. Arch Phys Med Rehabil 78:692–696PubMedCrossRefGoogle Scholar
  25. 24.
    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 51:958–963PubMedCrossRefGoogle Scholar
  26. 25.
    Weaver CM, Fleet JC (2004) Vitamin D requirements: current and future. Am J Clin Nutr 80(suppl 6):1735S–1739SPubMedGoogle Scholar
  27. 26.
    Frey-Rindova P, de Buin ED, Stussi 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 38:26–32PubMedCrossRefGoogle Scholar
  28. 27.
    Demulder A, Guns M, Ismail A, Wilmet E, Fondu P, Bergmann P (1998) Increased osteoclast-like cells formation in long-term bone marrow cultures from patients with a spinal cord injury. Calcif Tissue Int 63:396–400PubMedCrossRefGoogle Scholar
  29. 28.
    Garland DE, Stewart CA, Adkins RH, Hu SS, Rosen C, Liotta FJ, Weinstein DA (1992) Osteoporosis after spinal cord injury. J Orthop Res 10:371–378PubMedCrossRefGoogle Scholar
  30. 29.
    Wilmet E, Ismail AA, Heilporn A, Welraeds D, Bergmann P (1995) Longitudinal study of the bone mineral content and of soft tissue composition after spinal cord section. Paraplegia 33:674–687PubMedGoogle Scholar
  31. 30.
    de Bruin ED, Vanwanseele B, Dambacher MA, Dietz V, Stussi E (2005) Long-term changes in the tibia and radius bone mineral density following spinal cord injury. Spinal Cord 43:96–101PubMedCrossRefGoogle Scholar
  32. 31.
    Eser P, Schiessl H, Willnecker J (2004) Bone loss and steady state after spinal cord injury: a cross-sectional study using pQCT. J Musculoskelet Neuronal Interact 4:197–208PubMedGoogle Scholar
  33. 32.
    Modlesky C, Slade JM, Bickel CS, et al. (2005) Deteriorated geometric structure and strength of mid-femur in men with complete spinal cord injury. Bone 36:331–339PubMedCrossRefGoogle Scholar
  34. 33.
    Reid IR, Bown JP, Burckhardt P, Horowitz Z, Richardson P, Trechsel U, Widmer A, Devogelaer JP, Kaufman JM, Jaeger P, Body JJ, Bandi ML, Boell 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, Veruggen L, Meunier PJ (2002) Intravenous zoledronic acid in postmenopausal women with low bone mineral density. N Engl J Med 346:653–661PubMedCrossRefGoogle Scholar
  35. 34.
    Bauman WA, Wecht JMN, Kirshbalum S, Spungen AM, Momson N, Cirnigliaro C, Schwartz E (2005) Effect of pamidronate administration on bone in patients with acute spinal cord injury. J Rehabil Res Dev 42:305–314PubMedCrossRefGoogle Scholar
  36. 35.
    Giangregorio LM, Hicks A, Webber CE, Phillips SM, Crraven BC, Bugaresti JM, McCartney N (2005) Body weight supported treadmill training in acute spinal cord injury: impact on muscle and bone. Spinal Cord 43:347–351CrossRefGoogle Scholar
  37. 36.
    Tsuzuku S, Ikegami Y, Yabe K (1999) Bone mineral density differences between paraplegic and quadriplegic patients: a cross-sectional study. Spinal Cord 37:358–361PubMedCrossRefGoogle Scholar
  38. 37.
    Needham-Shropshire BM, Broton JC, Klose KJ, Lebwohl N, Guest RS, Jacobs PL (1997) Evaluation of a training program for persons with SCI paraplegia using the Parastep ambulation system: part 3. Lack of effect on bone mineral density. Arch Phys Med Rehab 78:799–803CrossRefGoogle Scholar
  39. 38.
    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 19:1067–1074PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • J. Shapiro
    • 1
  • B. Smith
    • 2
  • T. Beck
    • 3
  • P. Ballard
    • 2
  • M. Dapthary
    • 3
  • K. BrintzenhofeSzoc
    • 4
  • J. Caminis
    • 5
  1. 1.Department of Physical Medicine and RehabilitationKennedy Krieger InstituteBaltimoreUSA
  2. 2.National Rehabilitation HospitalWashingtonUSA
  3. 3.Department of RadiologyJohns Hopkins University Outpatient CenterBaltimoreUSA
  4. 4.Catholic University of AmericaWashingtonUSA
  5. 5.Novartis Pharmaceuticals, Inc.East HanoverUSA

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