Enhancement of Lumbar Fusion and Alleviation of Adjacent Segment Disc Degeneration by Intermittent PTH(1‐34) in Ovariectomized Rats

• Published in: Journal of bone and mineral research Vol. 31; no. 4; pp. 828 - 838
• Main Authors: Zhou, Zhuang, Tian, Fa‐Ming, Gou, Yu, Wang, Peng, Zhang, Heng, Song, Hui‐Ping, Shen, Yong, Zhang, Ying‐Ze, Zhang, Liu
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.04.2016
• Subjects: ADAMTS4 Protein - metabolism; Animals; BONE HISTOMORPHOMETRY; COLLAGEN; Collagen Type I - metabolism; Extracellular Matrix - metabolism; Extracellular Matrix - pathology; Female; Intervertebral Disc Degeneration - chemically induced; Intervertebral Disc Degeneration - metabolism; Intervertebral Disc Degeneration - surgery; Matrix Metalloproteinase 13 - metabolism; OSTEOPOROSIS; Ovariectomy; Parathyroid Hormone - adverse effects; Parathyroid Hormone - pharmacology; PRECLINICAL STUDIES; Rats; Rats, Sprague-Dawley; Spinal Fusion; μCT; BONE HISTOMORPHOMETRY; COLLAGEN; μCT; PRECLINICAL STUDIES; OSTEOPOROSIS
• ISSN: 0884-0431; 1523-4681
• DOI: 10.1002/jbmr.2736

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. © 2015 American Society for Bone and Mineral Research.