Enhancement of Lumbar Fusion and Alleviation of Adjacent Segment Disc Degeneration by Intermittent PTH(1-34) in Ovariectomized Rats.
Zhou Zhuang,Tian Fa-Ming,Gou Yu,Wang Peng,Zhang Heng,Song Hui-Ping,Shen Yong,Zhang Ying-Ze,Zhang Liu
Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research
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.
Longitudinal changes in bone mineral density, bone mineral content and bone area at the lumbar spine and hip in postmenopausal women, and the influence of abdominal aortic calcification.
Bristow Sarah M,Gamble Greg D,Horne Anne M,Reid Ian R
Longitudinal studies often report that spine bone mineral density (BMD), measured by DXA, is stable in older adults, which has been attributed to osteophyte development and the presence of aortic calcification. A decline in projected spine area as a result of loss of intervertebral disc height might also contribute to higher BMD. We utilised data from 297 postmenopausal women (mean 73 years) who had DXA measurements of the lumbar spine, total hip and femoral neck 5 years apart, and abdominal aortic calcification scoring from vertebral morphometry. BMD declined by -4.4% at the total hip and -3.9% at the femoral neck (p < 0.001), but did not change at the spine (-0.5%, p = 0.12). In contrast, bone mineral content (BMC) declined by -4.0% at the total hip, -2.5% at the femoral neck and -1.7% at the spine (all p < 0.001). Bone area increased by 0.5% at the hip and 1.6% at the femoral neck but declined by -1.2% at the spine (all p < 0.001). 43% of the cohort had abdominal aortic calcification (AAC) present at baseline. The presence of AAC at baseline was not related to changes in BMD or BMC at the total hip or femoral neck, nor to BMD at the spine. However, women with AAC present had a smaller loss of BMC at the spine than those without (-0.8% versus -2.4%, p = 0.03). AAC score increased more over 5 years among those with AAC at baseline than those without (0.28 versus 0.16, p = 0.036). Thus, the stability of spine BMD is the result of both a loss of projected bone area (as a result of intervertebral disc changes and/or a decrease in projected area of the vertebral bodies) and the effects of aortic calcification. Future clinical trials should consider assessing changes in spine BMC as a more informative index of spine mineral status.