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

Chang-Cheng Liu,Yu Gou,Peng Wang,Fa-Ming Tian,Zhuang Zhou,Wen-Ya Wang,Heng Zhang,Liu Zhang,Yong Shen,Ying-Ze Zhang

doi:10.1186/s12891-015-0788-7

Abstract

BackgroundIntervertebral 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.MethodsPosterolateral 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.ResultsHistological 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.ConclusionsThese 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.

Highlights

Intervertebral disc (IVD) degeneration and pathological changes in the spinal cord are major causes of back pain
For further insight into the mechanism of action of CT on disc Extracellular matrix (ECM) metabolism, we explored whether aggrecan, Col-II, Collagen type I (Col-I), matrix metalloproteinase-13 (MMP-13), and ADAMTS-4 participate in this process
Rats in the OVX + V and OVX + Posterolateral lumbar fusion (PLF) + V groups exhibited significantly lower bone mineral density (BMD) compared with the Sham + V and PLF + V groups; while OVX + PLF + sCT rats showed significantly higher BMD compared with OVX + PLF + V rats (P < 0.001, P = 0.001, P = 0.004, P = 0.011)

Summary

Introduction

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. We examined the effects of CT on IVD degeneration adjacent to a lumbar fusion in ovariectomized rats. Large numbers of patients undergoing lumbar fusion are the late-middle-aged and elderly population being treated for osteoporosis, which is characterized by a systemic impairment of bone mass and microarchitecture that increases the propensity of fragility fractures due to rapid bone absorption. It would be interesting if a treatment for osteoporosis could be effective for preventing ASDD after spinal fusion. To our knowledge, there are no available data on the effect of CT on ASDD induced by lumbar fusion in the ovariectomized rat

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