Osteoporosis International

, Volume 19, Issue 5, pp 645–652 | Cite as

Spinal cord injury causes rapid osteoclastic resorption and growth plate abnormalities in growing rats (SCI-induced bone loss in growing rats)

  • L. MorseEmail author
  • Y. D. Teng
  • L. Pham
  • K. Newton
  • D. Yu
  • W.-L. Liao
  • T. Kohler
  • R. Müller
  • D. Graves
  • P. Stashenko
  • R. Battaglino
Original Article



Spinal cord injury causes severe bone loss. We report osteoclast resorption with severe trabecular and cortical bone loss, decreased bone mineral apposition, and growth plate abnormalities in a rodent model of contusion spinal cord injury. These findings will help elucidate the mechanisms of osteoporosis following neurological trauma.


Limited understanding of the mechanism(s) that underlie spinal cord injury (SCI)-induced bone loss has led to few treatment options. As SCI-induced osteoporosis carries significant morbidity and can worsen already profound disability, there is an urgency to advance knowledge regarding this pathophysiology.


A clinically relevant contusion model of experimental spinal cord injury was used to generate severe lower thoracic SCI by weight-drop (10 g × 50 mm) in adolescent male Sprague-Dawley rats. Body weight and gender-matched naïve (no surgery) rats served as controls. Bone microarchitecture was determined by micro-computed tomographic imaging. Mature osteoclasts were identified by TRAP staining and bone apposition rate was determined by dynamic histomorphometry.


At 10 days post-injury we detected a marked 48% decrease in trabecular bone and a 35% decrease in cortical bone at the distal femoral metaphysis by micro-CT. A 330% increase in the number of mature osteoclasts was detected at the growth plate in the injured animals that corresponded with cellular disorganization at the chondro-osseous junction. Appositional growth studies demonstrated decreased new bone formation with a mineralization defect indicative of osteoblast dysfunction.


Contusion SCI results in a rapid bone loss that is the result of increased bone resorption and decreased bone formation.


Bone Osteoclast Osteoporosis Rehabilitation medicine Spinal cord injury 



We would like to thank Dr. M.van der Vlies and Justine Dobeck for technical assistance and the Swiss National Science Foundation.


Grant sponsor: NIH/NICHD Grant number K12 HD001097-08 (L.M.);

Grant sponsor: VABLR&D121F (Y.D.T.);

Grant sponsor: NIH Grant number R21NS53935 (Y.D.T.);

Grant sponsor: NIH/NICDR Grant number DE007378-18 (P.S.)


  1. 1.
    Szollar SM, Martin EM, Sartoris DJ, Parthemore JG, Deftos LJ (1998) Bone mineral density and indexes of bone metabolism in spinal cord injury. Am J Phys Med Rehabil 77(1):28–35, JanuaryPubMedCrossRefGoogle Scholar
  2. 2.
    Aluisio FV, Scully SP (1996) Acute hematogenous osteomyelitis of a closed fracture with chronic superinfection. Clin Orthop Relat Res 325:239–244, AprilPubMedCrossRefGoogle Scholar
  3. 3.
    Cochran TP, Bayley JC, Smith M (1988) Lower extremity fractures in paraplegics: pattern, treatment, and functional results. J Spinal Disord 1(3):219–223PubMedCrossRefGoogle Scholar
  4. 4.
    Garland DE, Saucedo T, Reiser TV (1986) The management of tibial fractures in acute spinal cord injury patients. Clin Orthop Relat Res 213:237–240, DecemberPubMedGoogle Scholar
  5. 5.
    Givre S, Freed HA (1989) Autonomic dysreflexia: a potentially fatal complication of somatic stress in quadriplegics. J Emerg Med 7(5):461–463, SeptemberPubMedCrossRefGoogle Scholar
  6. 6.
    Watson FM, Whitesides TE Jr (1976) Acute hematogenous osteomyelitis complicating closed fractures. Clin Orthop Relat Res 117:296–302, JunePubMedGoogle Scholar
  7. 7.
    Garland DE, Adkins RH, Kushwaha V, Stewart C (2004) Risk factors for osteoporosis at the knee in the spinal cord injury population. J Spinal Cord Med 27(3):202–206PubMedGoogle Scholar
  8. 8.
    Warden SJ, Bennell KL, Matthews B, Brown DJ, McMeeken JM, Wark JD (2002) Quantitative ultrasound assessment of acute bone loss following spinal cord injury: a longitudinal pilot study. Osteoporos Int 13(7):586–592, JulyPubMedCrossRefGoogle Scholar
  9. 9.
    Vico L, Collet P, Guignandon A, Lafage-Proust MH, Thomas T, Rehaillia M, Alexandre C (2000) Effects of long-term microgravity exposure on cancellous and cortical weight-bearing bones of cosmonauts. Lancet 355(9215):1607–1611, May 6PubMedCrossRefGoogle Scholar
  10. 10.
    Leblanc AD, Schneider VS, Evans HJ, Engelbretson DA, Krebs JM (1990) Bone mineral loss and recovery after 17 weeks of bed rest. J Bone Miner Res 5(8):843–850, AugustPubMedCrossRefGoogle Scholar
  11. 11.
    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(3):330–335, JunePubMedCrossRefGoogle Scholar
  12. 12.
    Dauty M, Perrouin VB, Maugars Y, Dubois C, Mathe JF (2000) Supralesional and sublesional bone mineral density in spinal cord-injured patients. Bone 27(2):305–309, AugustPubMedCrossRefGoogle Scholar
  13. 13.
    de Bruin ED, Frey-Rindova P, Herzog RE, Dietz V, Dambacher MA, Stussi E (1999) Changes of tibia bone properties after spinal cord injury: effects of early intervention. Arch Phys Med Rehabil 80(2):214–220, FebruaryPubMedCrossRefGoogle Scholar
  14. 14.
    Demirel G, Yilmaz H, Paker N, Onel S (1998) Osteoporosis after spinal cord injury. Spinal Cord 36(12):822–825, DecemberPubMedCrossRefGoogle Scholar
  15. 15.
    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(11):674–677, NovemberPubMedGoogle Scholar
  16. 16.
    Andresen EM, Patrick DL, Carter WB, Malmgren JA (1995) Comparing the performance of health status measures for healthy older adults. J Am Geriatr Soc 43(9):1030–1034, SeptemberPubMedGoogle Scholar
  17. 17.
    Karsenty G (2000) The central regulation of bone remodeling. Trends Endocrinol Metab 11(10):437–439, DecemberPubMedCrossRefGoogle Scholar
  18. 18.
    Battaglino R, Fu J, Spate U, Ersoy U, Joe M, Sedaghat L, Stashenko P (2004) Serotonin regulates osteoclast differentiation through its transporter. J Bone Miner Res 19(9):1420–1431, SeptemberPubMedCrossRefGoogle Scholar
  19. 19.
    Battaglino R, Vokes M, Schulze-Spate U, Sharma A, Graves D, Kohler T, Muller R, Yoganathan S, Stashenko P (2007) Fluoxetine treatment increases trabecular bone formation in mice. J Cell Biochem 100(6):1387–1394, April 15PubMedCrossRefGoogle Scholar
  20. 20.
    Cherruau M, Facchinetti P, Baroukh B, Saffar JL (1999) Chemical sympathectomy impairs bone resorption in rats: a role for the sympathetic system on bone metabolism. Bone 25(5):545–551, NovemberPubMedCrossRefGoogle Scholar
  21. 21.
    Cherruau M, Morvan FO, Schirar A, Saffar JL (2003) Chemical sympathectomy-induced changes in TH-, VIP-, and CGRP-immunoreactive fibers in the rat mandible periosteum: influence on bone resorption. J Cell Physiol 194(3):341–348, MarchPubMedCrossRefGoogle Scholar
  22. 22.
    Hill EL, Elde R (1991) Distribution of CGRP-, VIP-, D beta H-, SP-, and NPY-immunoreactive nerves in the periosteum of the rat. Cell Tissue Res 264(3):469–480, JunePubMedCrossRefGoogle Scholar
  23. 23.
    Hill EL, Turner R, Elde R (1991) Effects of neonatal sympathectomy and capsaicin treatment on bone remodeling in rats. Neuroscience 44(3):747–755PubMedCrossRefGoogle Scholar
  24. 24.
    Nockels R, Young W (1992) Pharmacologic strategies in the treatment of experimental spinal cord injury. J Neurotrauma 9(Suppl 1):S211–S217, MarchPubMedGoogle Scholar
  25. 25.
    Thompson MK, Tuma RF, Young WF (1999) The effects of pentoxifylline on spinal cord blood flow after experimental spinal cord injury. J Assoc Acad Minor Phys 10(1):23–26PubMedGoogle Scholar
  26. 26.
    Hulsebosch CE, Xu GY, Perez-Polo JR, Westlund KN, Taylor CP, McAdoo DJ (2000) Rodent model of chronic central pain after spinal cord contusion injury and effects of gabapentin. J Neurotrauma 17(12):1205–1217, DecemberPubMedCrossRefGoogle Scholar
  27. 27.
    Mills CD, Grady JJ, Hulsebosch CE (2001) Changes in exploratory behavior as a measure of chronic central pain following spinal cord injury. J Neurotrauma 18(10):1091–1105, OctoberPubMedCrossRefGoogle Scholar
  28. 28.
    Pikov V, Wrathall JR (2001) Coordination of the bladder detrusor and the external urethral sphincter in a rat model of spinal cord injury: effect of injury severity. J Neurosci 21(2):559–569, January 15PubMedGoogle Scholar
  29. 29.
    Pikov V, Wrathall JR (2002) Altered glutamate receptor function during recovery of bladder detrusor-external urethral sphincter coordination in a rat model of spinal cord injury. J Pharmacol Exp Ther 300(2):421–427, FebruaryPubMedCrossRefGoogle Scholar
  30. 30.
    Choi H, Liao WL, Newton KM, Onario RC, King AM, Desilets FC, Woodard EJ, Eichler ME, Frontera WR, Sabharwal S, Teng YD (2005) Respiratory abnormalities resulting from midcervical spinal cord injury and their reversal by serotonin 1A agonists in conscious rats. J Neurosci 25(18):4550–4559, May 4PubMedCrossRefGoogle Scholar
  31. 31.
    Teng YD, Lavik EB, Qu X, Park KI, Ourednik J, Zurakowski D, Langer R, Snyder EY (2002) Functional recovery following traumatic spinal cord injury mediated by a unique polymer scaffold seeded with neural stem cells. Proc Natl Acad Sci USA 99(5):3024–3029, March 5PubMedCrossRefGoogle Scholar
  32. 32.
    Ruegsegger P, Koller B, Muller R (1996) A microtomographic system for the nondestructive evaluation of bone architecture. Calcif Tissue Int 58(1):24–29, JanuaryPubMedCrossRefGoogle Scholar
  33. 33.
    Kohler T, Beyeler M, Webster D, Muller R (2005) Compartmental bone morphometry in the mouse femur: reproducibility and resolution dependence of microtomographic measurements. Calcif Tissue Int 77(5):281–290, NovemberPubMedCrossRefGoogle Scholar
  34. 34.
    Villanueva AR, Mehr LA (1977) Modifications of the Goldner and Gomori one-step trichrome stains for plastic-embedded thin sections of bone. Am J Med Technol 43(6):536–538, JunePubMedGoogle Scholar
  35. 35.
    Dietz V, Curt A (2006) Neurological aspects of spinal-cord repair: promises and challenges. Lancet Neurol 5(8):688–694, AugustPubMedCrossRefGoogle Scholar
  36. 36.
    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(3):339–349, MarchPubMedCrossRefGoogle Scholar
  37. 37.
    Duval-Beaupere G, Lougovoy J, Trocellier L, Lacert P (1983) Trunk and leg growth in children with paraplegia caused by spinal cord injury. Paraplegia 21(6):339–350, DecemberPubMedGoogle Scholar
  38. 38.
    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(2):197–198, JunePubMedGoogle Scholar
  39. 39.
    Eser P, Frotzler A, Zehnder Y, Schiessl H, Denoth J (2005) Assessment of anthropometric, systemic, and lifestyle factors influencing bone status in the legs of spinal cord injured individuals. Osteoporos Int 16(1):26–34, JanuaryPubMedCrossRefGoogle Scholar
  40. 40.
    Verhas M, Martinello Y, Mone M, Heilporn A, Bergmann P, Tricot A, Schoutens A (1980) Demineralization and pathological physiology of the skeleton in paraplegic rats. Calcif Tissue Int 30(1):83–90PubMedCrossRefGoogle Scholar
  41. 41.
    Takahashi H, Yamamuro T, Okumura H, Kasai R, Tada K (1990) Bone blood flow after spinal paralysis in the rat. J Orthop Res 8(3):393–400, MayPubMedCrossRefGoogle Scholar
  42. 42.
    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(5):396–400, NovemberPubMedCrossRefGoogle Scholar
  43. 43.
    Serre CM, Farlay D, Delmas PD, Chenu C (1999) Evidence for a dense and intimate innervation of the bone tissue, including glutamate-containing fibers. Bone 25(6):623–629, DecemberPubMedCrossRefGoogle Scholar
  44. 44.
    Chenu C (2002) Glutamatergic regulation of bone resorption. J Musculoskelet Neuronal Interact 2(5):423–431, SeptemberPubMedGoogle Scholar
  45. 45.
    Lundberg P, Lerner UH (2002) Expression and regulatory role of receptors for vasoactive intestinal peptide in bone cells. Microsc Res Tech 58(2):98–103, July 15PubMedCrossRefGoogle Scholar
  46. 46.
    Adam C, Llorens A, Baroukh B, Cherruau M, Saffar JL (2000) Effects of capsaicin-induced sensory denervation on osteoclastic resorption in adult rats. Exp Physiol 85(1):62–66, JanuaryPubMedCrossRefGoogle Scholar

Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2007

Authors and Affiliations

  • L. Morse
    • 1
    Email author
  • Y. D. Teng
    • 1
    • 2
    • 3
  • L. Pham
    • 6
  • K. Newton
    • 2
    • 3
  • D. Yu
    • 2
    • 3
  • W.-L. Liao
    • 1
    • 3
  • T. Kohler
    • 4
  • R. Müller
    • 4
  • D. Graves
    • 5
  • P. Stashenko
    • 6
  • R. Battaglino
    • 6
  1. 1.Department of Physical Medicine and RehabilitationHarvard Medical School and Spaulding Rehabilitation HospitalBostonUSA
  2. 2.Department of NeurosurgeryHarvard Medical School and Brigham and Women’s Hospital/Children’s HospitalBostonUSA
  3. 3.Division of Spinal Cord Injury ResearchVA Boston Healthcare SystemBostonUSA
  4. 4.Institute for BiomechanicsETH ZurichZurichSwitzerland
  5. 5.Boston University School of Dental MedicineBostonUSA
  6. 6.Department of Cytokine BiologyForsyth InstituteBostonUSA

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