Protective effect of calcitonin on lumbar fusion-induced adjacent-segment disc degeneration in ovariectomized rat

BMC Musculoskeletal Disorders

Liu Zhang⁴  Ying-Ze Zhang¹  Yong Shen¹  Wen-Ya Wang³  Heng Zhang⁴  Yu Gou⁴  Peng Wang⁴  Zhuang Zhou⁴  Fa-Ming Tian²  Chang-Cheng Liu¹ 

[1]Orthopaedic Research Institution of Hebei, Third Hospital of Hebei Medical University, Shijiazhuang 050017, P.R. China

[2]Medical Research Center, North China University of Science and Technology, Tangshan 063000, P. R. China

[3]Department of Pathology, School of Basic Medical Sciences, North China University of Science and Technology, Tangshan 063000, P. R. China

[4]Department of Orthopedic Surgery, Affiliated Hospital of North China University of Science and Technology, No. 73 Jianshe South Rd., Tangshan 063000, Hebei, P.R. China

关键词: Micro-computed tomography;    Calcitonin;    Osteoporosis;    Adjacent-segment disc degeneration;    Lumbar fusion;   

Others  :  1234027
DOI  :  10.1186/s12891-015-0788-7

 received in 2015-07-22, accepted in 2015-10-23,  发布年份 2015

【 摘 要 】

Background

Intervertebral disc (IVD) degeneration and pathological changes in the spinal cord are major causes of back pain. In addition to its well-established anti-resorptive effect on bone, calcitonin (CT) potentially exerts protective effects on IVD degeneration in ovariectomized rats. However, possible therapeutic effects of CT on lumbar fusion-induced adjacent-segment disc degeneration (ASDD) have not been investigated yet. In this study, we examined the effects of CT on IVD degeneration adjacent to a lumbar fusion in ovariectomized rats.

Methods

Posterolateral lumbar fusion (PLF) at L4–5 was performed 4 weeks after ovariectomy (OVX) or sham surgery in female Sprague–Dawley rats. Following PLF + OVX, rats received either salmon CT (OVX + PLF + sCT, 16 IU/Kg/2d) or vehicle (OVX + PLF + V) treatment for 12 weeks; the remaining rats were divided into Sham + V, OVX + V, and PLF + V groups. Fusion status was analyzed by manual palpation and radiography. Adjacent segment disc was assessed by histological, histomorphometric, immunohistochemical analysis. L6 vertebrae microstructures were evaluated by micro-computed tomography.

Results

Histological analysis showed more severe ASDD occurred in OVX + PLF + V rats compared with the OVX + V or PLF + V groups. CT treatment suppressed the score for ASDD, increased disc height, and decreased the area of endplate calcification. Immunohistochemical staining demonstrated that CT decreased the expression of collagen type-I, matrix metalloproteinase-13, and a disintegrin and metalloproteinase with thrombospondin motifs-4, whereas it increased the expression of collagen type-II and aggrecan in the disc. Micro-computed tomography indicated that CT increased bone mass and improved the microstructure of the L6 vertebrae.

Conclusions

These results suggest that CT can prevent ASDD, induce beneficial changes in IVD metabolism, and inhibit deterioration of the trabecular microarchitecture of vertebrae in osteoporotic rats with lumbar fusion.

【 授权许可】

   
2015 Liu et al.

【 图 表 】

Fig. 1.

Fig. 2.

Fig. 3.

Fig. 4.

Fig. 5.

Fig. 6.

Fig. 7.

Fig. 8.

【 参考文献 】

• [1]Deiner S, Westlake B, Dutton RP. Patterns of surgical care and complications in elderly adults. J Am Geriatr Soc. 2014; 62(5):829-835.
• [2]Ong KL, Auerbach JD, Lau E, Schmier J, Ochoa JA. Perioperative outcomes, complications, and costs associated with lumbar spinal fusion in older patients with spinal stenosis and spondylolisthesis. Neurosurg Focus. 2014; 36(6):E5.
• [3]Boden SD. Overview of the biology of lumbar spine fusion and principles for selecting a bone graft substitute. Spine (Phila Pa 1976). 2002; 27(16s):S26-S31.
• [4]Chen CS, Cheng CK, Liu CL. A biomechanical comparison of posterolateral fusion and posterior fusion in the lumbar spine. J Spinal Disord Tech. 2002; 15(1):53-63.
• [5]Molz FJ, Partin JI, Kirkpatrick JS. The acute effects of posterior fusion instrumentation on kinematics and intradiscal pressure of the human lumbar spine. J Spinal Disord Tech. 2003; 16(2):171-179.
• [6]Park P, Garton HJ, Gala VC, Hoff JT, Mcgilltcuddy JE. Adjacent segment disease after lumbar or lumbosacral fusion: review of the literature. Spine (Phila Pa 1976). 2004; 29(17):1938-1944.
• [7]Sexton PM, Findlay DM, Martin TJ. Calcitonin. Curr Med Chem. 1999; 6(11):1067-1093.
• [8]Mehta NM, Malootian A, Gilligan JP. Calcitonin for osteoporosis and bone pain. Curr Pharm Des. 2003; 9(32):2659-2676.
• [9]Sondergaard BC, Wulf H, Henriksen K, Schaller S, Oestergaard S, Qvist P et al.. Calcitonin directly attenuates collagen type II degradation by inhibition of matrix metalloproteinase expression and activity in articular chondrocytes. Osteoarthritis Cartilage. 2006; 14(8):759-768.
• [10]Luo Y, Zhang L, Wang WY, Hu QF, Song HP, Zhang YZ. The inhibitory effect of salmon calcitonin on intervertebral disc degeneration in an ovariectomized rat model. Eur Spine J. 2015; 24(8):1691-1701.
• [11]Lotz JC, Fields AJ, Liebenberg EC. The role of the vertebral end plate in low back pain. Global Spine J. 2013; 3(3):153-164.
• [12]Gruber HE, Ashraf N, Kilburn J, Williams C, Norton HJ, Gordon BE et al.. Vertebral endplate architecture and vascularization: application of micro-computerized tomography, a vascular tracer, and immunocytochemistry in analyses of disc degeneration in the aging sand rat. Spine (Phila Pa 1976). 2005; 30(23):2593-2600.
• [13]Wang Y, Battié MC, Boyd SK, Videman T. The osseous endplates in lumbar vertebrae: thickness, bone mineral density and their associations with age and disk degeneration. Bone. 2011; 48(4):804-809.
• [14]Le Maitre CL, Pockert A, Buttle DJ, Freemont AJ, Hoyland JA. Matrix synthesis and degradation in human intervertebral disc degeneration. Biochem Soc Trans. 2007; 35(Pt 4):652-655.
• [15]Dimar JR, Ante WA, Zhang YP, Glassman SD. The effects of nonsteroidal anti-inflammatory drugs on posterior spinal fusions in the rat. Spine (Phila Pa 1976). 1996; 21(16):1870-1876.
• [16]O’Loughlin PF, Cunningham ME, Bukata SV, Tomin E, Poynton AR, Doty SB et al.. Parathyroid hormone (1–34) augments spinal fusion, fusion mass volume, and fusion mass quality in a rabbit spinal fusion model. Spine (Phila Pa 1976). 2009; 34(2):121-130.
• [17]Abe Y, Takahata M, Ito M, Irie K, Abumi K, Minami A. Enhancement of graft bone healing by intermittent administration of human parathyroid hormone (1–34) in a rat spinal arthrodesis model. Bone. 2007; 41(5):775-785.
• [18]Wang T, Zhang L, Huang C, Cheng AG, Dang GT. Relationship between osteopenia and lumbar intervertebral disc degeneration in ovariectomized rats. Calcif Tissue Int. 2004; 75(3):205-213.
• [19]Allon AA, Aurouer N, Yoo BB, Liebenberg EC, Buser Z, Lotz JC. Structured coculture of stem cells and disc cells prevent disc degeneration in a rat model. Spine J. 2010; 10(12):1089-1097.
• [20]Phillips FM, Reuben J, Wetzel FT. Intervertebral disc degeneration adjacent to a lumbar fusion. An experimental rabbit model. J Bone Joint Surg (Br). 2002; 84(2):289-294.
• [21]Higashino K, Hamasaki T, Kim JH, Okada M, Yoon ST, Boden SD et al.. Do the adjacent level intervertebral discs degenerate after a lumbar spinal fusion? An experimental study using a rabbit model. Spine (Phila Pa 1976). 2010; 35(22):E1144-E1152.
• [22]Wang Y, Boyd SK, Battié MC, Yasui Y, Videman T. Is greater lumbar vertebral BMD associated with more disk degeneration? A study using μCT and discography. J Bone Miner Res. 2011; 26(11):2785-2791.
• [23]Wang YX, Griffith JF, Ma HT, Kwok AW, Leung JC, Yeung DK et al.. Relationship between gender, bone mineral density, and disc degeneration in the lumbar spine: a study in elderly subjects using an eight-level MRI-based disc degeneration grading system. Osteoporos Int. 2011; 22(1):91-96.
• [24]Wang YX, Griffith JF. Effect of menopause on lumbar disc degeneration: potential etiology. Radiology. 2010; 257(2):318-320.
• [25]Baron YM, Brincat MP, Galea R, Calleja N. Intervertebral disc height in treated and untreated overweight post-menopausal women. Hum Reprod. 2005; 20(12):3566-3570.
• [26]Zheng SX, Vrindts Y, Lopez M, De Groote D, Zangerle PF, Collette J et al.. Increase in cytokine production (IL-1b, IL-6, TNF-a but not IFN-g, GM-CSF or LIF) by stimulated whole blood cells in postmenopausal osteoporosis. Maturitas. 1997; 26(1):63-71.
• [27]Phillips KL, Jordan-Mahy N, Nicklin MJ, Maitre CL. Interleukin-1 receptor antagonist deficient mice provide insights into pathogenesis of human intervertebral disc degeneration. Ann Rheum Dis. 2013; 72(11):1860-1867.
• [28]Séguin CA, Pilliar RM, Roughley PJ, Kandel RA. Tumor necrosis factor-alpha modulates matrix production and catabolism in nucleus pulposus tissue. Spine (Phila Pa 1976). 2005; 30(17):1940-1948.
• [29]Stokes IA, Iatridis JC. Mechanical conditions that accelerate intervertebral disc degeneration: overload versus immobilization. Spine (Phila Pa 1976). 2004; 29(23):2724-2732.
• [30]Babat LB, McLain R, Milks R, Ferrara L, Sohn MJ. The effects of the antiresorptive agents calcitonin and pamidronate on spine fusion in a rabbit model. Spine J. 2005; 5(5):542-547.
• [31]Liu Y, Fan Y, Cao D, Zhang J, Wu Z, Qiu G. Calcitonin enhanced lumbar spinal fusion in a New Zealand rabbit model: a study with morphologic and molecular analysis. Spine (Phila Pa 1976). 2012; 37(3):E139-E146.
• [32]Li M, Shen Y, Burton KW, DeLuca PP, Mehta RC, Baumann BD et al.. A comparison of the skeletal effects of intermittent and continuous administration of calcitonin in ovariectomized rats. Bone. 1996; 18(4):375-380.
• [33]Shen Y, Li M, Wronski TJ. Calcitonin provides complete protection against cancellous bone loss in the femoral neck of ovariectomized rats. Calcif Tissue Int. 1997; 60(5):457-461.