title: Enhancement of Lumbar Fusion and Alleviation of Adjacent Segment Disc Degeneration by Intermittent PTH(1-34) in Ovariectomized Rats.
abstract: Osteoporosis, which is prevalent in postmenopausal or aged populations, is thought to be a contributing factor to adjacent segment disc degeneration (ASDD), and the incidence and extent of ASDD may be augmented by osteopenia. Parathyroid hormone (PTH) (1-34) has already been shown to be beneficial in osteoporosis, lumbar fusion and matrix homeostasis of intervertebral discs. However, whether PTH(1-34) has a reversing or retarding effect on ASDD in osteopenia has not been confirmed. In the present study, we evaluated the effects of intermittent PTH(1-34) on ASDD in an ovariectomized (OVX) rat model. One hundred 3-month-old female Sprague-Dawley rats underwent L4 -L5 posterolateral lumbar fusion (PLF) with spinous-process wire fixation 4 weeks after OVX surgery. Control groups were established accordingly. PTH(1-34) was intermittently administered immediately after PLF surgery and lasted for 8 weeks using the following groups (n = 20) (V = vehicle): Sham+V, OVX+V, Sham+PLF+V, OVX+PLF+V, OVX+PLF+PTH. The fused segments showed clear evidence of eliminated motion on the fusion-segment based on manual palpation. Greater new bone formation in histology was observed in PTH-treated animals compared to the control group. The extent of ASDD was significantly increased by ovariotomy. Intermittent PTH(1-34) significantly alleviated ASDD by preserving disc height, microvessel density, relative area of vascular buds, endplate thickness and the relative area of endplate calcification. Moreover, protein expression results showed that PTH(1-34) not only inhibited matrix degradation by decreasing MMP-13, ADAMTS-4 and Col-I, but also promote matrix synthesis by increasing Col-II and Aggrecan. In conclusion, PTH(1-34), which effectively improves lumbar fusion and alleviates ASDD in ovariectomized rats, may be a potential candidate to ameliorate the prognosis of lumbar fusion in osteopenia.
authors.affiliation: Department of Orthopedic Surgery, The Affiliated Hospital of North China University of Science and Technology, Tangshan, China.
authors.forename: Zhuang
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: Medical Research Center, North China University of Science and Technology, Tangshan, China.
authors.forename: Fa-Ming
authors.initials: FM
authors.lastname: Tian
authors.affiliation: Department of Orthopedic Surgery, The Affiliated Hospital of North China University of Science and Technology, Tangshan, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Gou
authors.affiliation: Department of Orthopedic Surgery, The Affiliated Hospital of North China University of Science and Technology, Tangshan, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Wang
authors.affiliation: Department of Orthopedic Surgery, The Affiliated Hospital of North China University of Science and Technology, Tangshan, China.
authors.forename: Heng
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Orthopedic Surgery, The Affiliated Hospital of North China University of Science and Technology, Tangshan, China.
authors.forename: Hui-Ping
authors.initials: HP
authors.lastname: Song
authors.affiliation: Department of Orthopedic Surgery, The Third Hospital of Hebei Medical University, Shijiazhuang, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Shen
authors.affiliation: Department of Orthopedic Surgery, The Third Hospital of Hebei Medical University, Shijiazhuang, China.
authors.forename: Ying-Ze
authors.initials: YZ
authors.lastname: Zhang
authors.affiliation: Department of Orthopedic Surgery, The Affiliated Hospital of North China University of Science and Technology, Tangshan, China.
authors.forename: Liu
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000071121:ADAMTS4 Protein / Q000378:metabolism; D000818:Animals; D024042:Collagen Type I / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism / Q000473:pathology; D005260:Female; D055959:Intervertebral Disc Degeneration / Q000139:chemically induced / Q000378:metabolism / Q000601:surgery; D053509:Matrix Metalloproteinase 13 / Q000378:metabolism; D010052:Ovariectomy; D010281:Parathyroid Hormone / Q000009:adverse effects* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013123:Spinal Fusion
chemical_list: D024042:Collagen Type I; D010281:Parathyroid Hormone; C571365:ADAMTS4 protein, rat; D053509:Matrix Metalloproteinase 13; C507083:Mmp13 protein, rat; D000071121:ADAMTS4 Protein
keywords: BONE HISTOMORPHOMETRY; COLLAGEN; OSTEOPOROSIS; PRECLINICAL STUDIES; μCT