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: Zhuang Zhou, Fa-Ming Tian, Yu Gou, Peng Wang, Heng Zhang, Hui-Ping Song, Yong Shen, Ying-Ze Zhang, Liu Zhang
• Journal: Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research (J Bone Miner Res) Vol. 31 Issue 4 Pg. 828-38 (Apr 2016) ISSN: 1523-4681 [Electronic] United States
• PMID: 26542457 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 American Society for Bone and Mineral Research.

Chemical References

• Collagen Type I
• Parathyroid Hormone
• ADAMTS4 protein, rat
• Matrix Metalloproteinase 13
• Mmp13 protein, rat
• ADAMTS4 Protein

Topics

• ADAMTS4 Protein (metabolism)
• Animals
• Collagen Type I (metabolism)
• Extracellular Matrix (metabolism, pathology)
• Female
• Intervertebral Disc Degeneration (chemically induced, metabolism, surgery)
• Matrix Metalloproteinase 13 (metabolism)
• Ovariectomy
• Parathyroid Hormone (adverse effects, pharmacology)
• Rats
• Rats, Sprague-Dawley
• Spinal Fusion