Combination therapy with low-dose teriparatide and zoledronate contributes to fracture healing on rat femoral fracture model.
Combination therapy with low-dose teriparatide and zoledronate contributes to fracture healing on rat femoral fracture model.
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DOI：
10.1186/s13018-018-0917-8
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发表时间：
2018-10-25
影响因子：
2.6
通讯作者：
Tsumura H
中科院分区：
文献类型：
--
作者：
Tsubouchi Y;Ikeda S;Kataoka M;Tsumura H
骨折愈合延迟或不愈合可能会造成毁灭性的并发症。最近的研究报道，在大鼠骨折模型中，特立帕肽（TP）对愈伤组织形成和机械强度有效，唑来膦酸（ZA）增加了骨折部位的愈伤组织大小和抵抗力。本研究评估了低剂量TP和ZA联合治疗对骨折愈合的影响。术后1周起，将大鼠分为以下5组，给予TP（每周给药5次）和ZA（单次给药0.1 mg/kg）：TP 1 μg组{T(1)：TP 1 μg/kg}、ZA组（ZA：0.1 mg/kg）、TP1 μg+ZA组{T(1)+ZA：TP 1μg/kg+ZA}、TP 10μg+ZA组{T(10)+ZA：TP 10μg/kg + ZA}和对照组（C：施用生理盐水）。手术后 7 周切除 Rt 股骨；骨融合通过软 X 射线图像按 4 点等级进行评估。对脱矿和非脱矿标本进行组织病理学检查。此外，对所有标本进行了射线照相联合量表。骨融合率方面，C、T(1)、ZA、T(1)+ZA、T(10)+ZA组分别为20.0%、55.6%、70.0%、70.0%、80.0%，采用4分制，各组分别为0.50、1.56、2.00、2.60、2.80分，分别。 T(1)+ZA 和 T(10)+ZA 组中愈伤组织体积分别显着增加至 16.66 mm2 和 17.75 mm2，而 C 组中为 10.65 mm2 (p<0.05)。此外，还观察到T(10)+ZA组的愈伤组织面积显着增加至78.78%，而C组和T(1)+ZA组的愈伤组织面积分别为54.63%和44.11%(p < 0.01)。组织病理学观察，C组骨连接处可见软骨组织及未成熟骨痂形成；然而，在ZA、T(1)+ZA和T(10)+ZA组中观察到成熟愈伤组织的骨桥形成。提示小剂量TP与ZA联合应用可能达到骨折延迟愈合的治疗效果。我们希望联合治疗能够成为新的治疗策略之一。
Delay in fracture healing or non-union can be devastating complication. Recent studies have reported that teriparatide (TP) demonstrated effectively on callus formation and mechanical strength and zoledronate (ZA) increased the callus size and resistance at the fracture site in rat fracture model. In this study, the effects of combination therapy with low dose TP and ZA on fracture healing was evaluated. From 1 week post-operation, TP (5 times a week administration) and ZA (0.1 mg/kg single administration) were administered by dividing the rats into the following five groups: TP 1 μg group {T(1): TP 1 μg/kg}, ZA group (ZA:0.1 mg/kg), TP1 μg+ZA group {T(1)+ZA: TP 1 μg/kg+ZA}, TP 10 μg+ZA group {T(10)+ZA: TP 10 μg/kg + ZA}, and control group (C: administered saline). Rt femurs were excised 7 weeks after the surgery; bone fusions were evaluated with soft X-ray images on a 4-point scale. And the histopathological examination was performed in demineralized and non-demineralized specimens. Furthermore, the Radiographic Union Scale was conducted in all specimens. About the bone fusions rates, C, T(1), ZA, T(1)+ZA, and T(10)+ZA groups demonstrated 20.0%, 55.6%, 70.0%, 70.0%, and 80.0%, respectively, and with 4-point scale, each group was 0.50, 1.56, 2.00, 2.60, and 2.80 points, respectively. The callus volume was significantly increased to 16.66 mm2 and 17.75 mm2 in the T(1)+ZA and T(10)+ZA groups, respectively, while 10.65 mm2 (p < 0.05) in the C group. Furthermore, the callus area in the T(10)+ZA group was also observed to have significantly increased to 78.78%, compared with 54.63% and 44.11% in the C and T(1)+ZA groups, respectively (p < 0.01). Histopathologically, cartilage tissue and immature callus formation were observed at the bone junction in the C group; however, the osseous bridge formation of mature callus was observed in the ZA, T(1)+ZA, and T(10)+ZA groups. It is suggested that administration of low dose TP and ZA in combination may lead to the treatment of delayed union of fracture. We hope the combination treatment may become one of new therapeutic strategy.
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影响因子：
6.2
作者：
Murphy, Ciara M.;Schindeler, Aaron;Little, David G.
通讯作者：
Little, David G.
影响因子：
6.2
作者：
Andreassen, TT;Ejersted, C;Oxlund, H
通讯作者：
Oxlund, H
影响因子：
4
作者：
Chapurlat, RD;Palermo, L;Cummings, SR
通讯作者：
Cummings, SR
影响因子：
2.8
作者：
Matos, Marcos Almeida;Tannuri, Uenis;Guarniero, Roberto
通讯作者：
Guarniero, Roberto
DOI：
10.1038/nrrheum.2014.164
发表时间：
2015-01
期刊：
Nature reviews. Rheumatology
影响因子：
--
作者：
通讯作者：
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