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 L 4 -L 5 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 ¼ 20) (V ¼ vehicle): ShamþV, OVXþV, ShamþPLFþV, OVXþPLFþV, OVXþPLFþPTH. 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.

Denosumab Alleviates Intervertebral Disc Degeneration Adjacent to a Lumbar Fusion by Inhibiting Endplate Osteochondral Remodeling and Vertebral Osteoporosis in Ovariectomized Rats

“…The immunohistochemical staining and RT-PCR results of nucleus pulposus tissue con rmed that, compared to the Sham group, the expression level of aggrecan was signi cantly lower whereas the expression levels of ADAMT-4 and MMP-13 were signi cantly higher in OVX + PLF group. These results are basically consistent with the previous results [2,3,23].…”

“…In addition, after lumbar fusion, vertebral osteoporosis is not only an important risk factor for postoperative vertebral nonunion complications but also leads to increased bone conversion rate and biomechanical changes, resulting in microenvironmental changes, thereby accelerating the development of ASDD [2,[27][28][29]. We performed TRAP staining on histological sections and found an increased number of osteoclasts, suggesting a high conversion rate of bone and cartilage at the intervertebral disc and vertebral interface in the ASDD model.…”

“…Lumbar fusion is a widely used, principal operation for spinal diseases that effectively relieves the symptoms of lower back pain [1]. Adjacent intervertebral disc degeneration (ASDD), one of the important and prevalent complications of lumbar fusion, seriously affects long-term clinical outcomes for patients [2], requires secondary operations, and increases the costs [1]. The clinical treatment of ASDD is limited because it cannot fully relieve the symptoms induced by degeneration of the intervertebral disc, and it cannot fundamentally reverse ASDD.…”

In vivo transplantation of 3D encapsulated ovarian constructs in rats corrects abnormalities of ovarian failure

“…In conclusion, this study highlights the potential utility of cHRT for the treatment and study of conditions associated with functional loss of the ovaries. Although longer-term studies would be of future interest, the 90-day duration of this rodent model study is consistent with others investigating osteoporosis in an ovariectomy model 59 – 62 . However, while our study provides a proof-of-concept for cHRT, it suffers the limitation that it is only an isogeneic-based construct implantation.…”

Ciliary parathyroid hormone signaling activates transforming growth factor-β to maintain intervertebral disc homeostasis during aging

“… 46 PTH helps in retarding intervertebral disc degeneration by significantly decreasing calcification in discs through both MAPK and PKA signaling pathways. 46 iPTH injection improves the adjacent segment disc degeneration by enhancing lumber fusion 47 and alleviates disc degeneration in ovariectomized osteoporotic mice by up-regulation of Wnt/β-catenin pathway. 48 In this study, we demonstrate that PTH1R is expressed in the NP cells of notochordal origin to maintain disc homeostasis particularly during aging by directly activating TGF-β signaling in NP cells in addition to its expression in vertebral bodies and endplates.…”