Effect of a selective estrogen receptor modulator on bone formation in osteoporotic spine fusion using an ovariectomized rat model

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• 作者：Sung Bae Park ; MD ; PhD^a ; Chi Heon Kim ; MD ; PhD^b ; Minyoung Hong ; MS^b ; Hee-Jin Yang ; MD ; PhD^a ; Chun Kee Chung ; MD ; PhD^b ; ^c ; ^d ; ^{chungc@snu.ac.kr" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Fusion ; Osteoporosis ; Rat ; Selective estrogen receptor modulator ; Spine ; Trabecular
• 刊名：The Spine Journal
• 出版年：2016
• 出版时间：1 January 2016
• 年：2016
• 卷：16
• 期：1
• 页码：72-81
• 全文大小：1848 K

文摘

Selective estrogen receptor modulators (SERMs) are drugs used to treat osteoporosis. Selective estrogen receptor modulators improve bone mineral density and bone mechanical strength. However, there is a lack of data on the effect of SERMs on osteoporotic spinal fusion.

Purpose

This study aimed to investigate whether treatment with a SERM enhances spinal fusion in an ovariectomized (OVX) rat model.

Study Design

An in vivo animal study was carried out.

Methods

Female Sprague Dawley rats (n=90) were OVX or sham-operated, and randomized into three groups: control (sham-operated+fusion procedure+saline administration), OVX (OVX+fusion procedure+saline administration), and SERM (OVX+fusion procedure+administration of SERM). Eight weeks after OVX, a bilateral lumbar spinal fusion procedure was performed using autologous iliac bone. In each group, gene expression was evaluated at 2, 4, and 8 weeks after the fusion procedure, histologic analysis was performed at 4 and 8 weeks after the procedure, and bone parameters were measured by micro-computed tomography at 2 days, 4 weeks, and 8 weeks after the procedure.

Results

Bone mineral density and trabecular quality of the vertebral body were significantly higher in the SERM group compared with the OVX group 16 weeks after OVX. The fusion rate and bone volume ratio were higher in the fusion bed of the SERM group compared with the OVX group 8 weeks after the fusion procedure. Real-time reverse transcription polymerase chain reaction at 4 and 8 weeks after the fusion procedure showed increased expression of the genes for osteoblast-related markers (alkaline phosphatase, osteocalcin, runt-related transcription factor 2, and transforming growth factor) in the SERM group compared with the OVX group. The OVX group showed sparse bone mass between transverse processes. By contrast, the SERM group exhibited a compact bridging fusion mass within the fusion bed at 8 weeks after the fusion procedure.

Conclusions

Selective estrogen receptor modulator treatment improved the trabecular quality of the vertebral body, enhanced spinal fusion, and increased the amount of compact bone mass within the fusion bed in rats that had received an ovariectomy. Therapeutic SERM treatment may be recommended to improve the fusion rate in osteoporotic patients who undergo spinal fusion.