Department of Orthopaedic Surgery, Faculty of Medicine, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033, Japan.
Department of Developmental Biology of Hard Tissue, Hokkaido University, Graduate School of Dental Medicine, Kita 13 Nishi 7, Kita-ku, Sapporo 060-8586, Japan.
Bone. 2018 Feb;107:18-26. doi: 10.1016/j.bone.2017.10.021. Epub 2017 Nov 2.
We examined the effect of teriparatide, and switching from teriparatide to anti-RANKL (receptor activator of nuclear factor κB ligand) monoclonal antibody, in ovariectomized mice. Twelve-week-old female C57BL/6 mice were ovariectomized or sham operated. Four weeks after surgery, ovariectomized mice were subjected to one of the following four treatments: phosphate-buffered saline (PBS) for 8weeks; teriparatide for 4weeks followed by PBS for 4weeks (PTH4W group); teriparatide for 8weeks (PTH8W group); or teriparatide for 4weeks followed by anti-RANKL antibody (single subcutaneous injection of 5mg/kg) (SWITCH group). Twelve weeks after the operation, bone mineral density was increased in PTH8W and SWITCH groups to broadly comparable levels, but these were significantly decreased in the PTH4W group after discontinuation of teriparatide. Histomorphometric analysis demonstrated that cancellous bone formation and resorption were profoundly suppressed in the SWITCH group. Bone formation was also suppressed on the endocortical surface of cortical bone but was maintained on the periosteal surface. Anti-RANKL antibody suppressed osteoclast activity immediately after treatment, while bone formation was only gradually decreased. These results suggest that anti-RANKL antibody may be a therapeutic option after discontinuation of teriparatide therapy.
我们研究了特立帕肽（teriparatide）及其与抗核因子κB 配体受体激活剂（receptor activator of nuclear factor κB ligand）单克隆抗体（antibody）转换疗法对去卵巢小鼠的影响。12 周龄雌性 C57BL/6 小鼠接受卵巢切除术或假手术。手术后 4 周，将去卵巢小鼠分为以下 4 种处理组之一：磷酸盐缓冲液（phosphate-buffered saline，PBS）8 周；特立帕肽 4 周，然后 PBS 4 周（PTH4W 组）；特立帕肽 8 周（PTH8W 组）；或特立帕肽 4 周，然后抗 RANKL 抗体（单剂量皮下注射 5mg/kg）（SWITCH 组）。手术后 12 周，PTH8W 和 SWITCH 组的骨密度增加至大致相当的水平，但在停用特立帕肽后，PTH4W 组的骨密度显著降低。组织形态计量学分析表明，SWITCH 组松质骨形成和吸收受到严重抑制。皮质骨的内骨表面的骨形成也受到抑制，但骨膜表面的骨形成得到维持。抗 RANKL 抗体在治疗后立即抑制破骨细胞活性，而骨形成只是逐渐减少。这些结果表明，抗 RANKL 抗体可能是特立帕肽治疗停药后的一种治疗选择。
