Department of Trauma Surgery and Reconstructive Surgery, University of Goettingen, Robert-Koch 40, 37075 Goettingen, Germany.
Bone. 2010 Sep;47(3):480-92. doi: 10.1016/j.bone.2010.05.013. Epub 2010 May 16.
Three experiments were conducted to investigate the effect of intermittent administration of parathyroid hormone (PTH) (1-34) applied at different regimes on fracture healing and muscle in healthy and ovariectomized (Ovx at 3 months of age) rats. Five-month old rats underwent bilateral transverse metaphyseal osteotomy of tibia and were divided into groups (12 rats each). In Exp 1, Ovx rats were either treated with PTH (7x/w, 1-35d), with oral estradiol-17beta-benzoate (0.4 mg/kg BW, 1-35d) or untreated. In Exp. 2, there were 3 groups: healthy untreated or treated with PTH (5x/w, 1-35d or 7-35d). In Exp. 3, there were 7 groups: healthy, Ovx, "healthy PTH 5x/w 7-35d", "Ovx PTH 5x/w 7-35d, 14-35d or 14-28d", "Ovx PTH every other day 7-35d". Single dosage of PTH was 40 microg/kg BW. After 35 days of healing one tibia was analyzed by computed tomographical, biomechanical, histological analyses. The other tibia was used in analyses of Alp, Oc, Trap 1, Igf-1, Rankl, Opg genes (Exp.2, 3). Serum Oc and Alp were measured. Body, uterus weight was recorded. M. gastrocnemius was analyzed for weight (Exp. 2), fiber size and mitochondrial respiratory activity (MRA) (Exp.3). Estrogen enhanced uterus weight, prevented body increase, however, did not improve bone healing in Ovx rats (Exp. 1). PTH administration from days 1 and 7 improved bone parameters in all rats regardless of the application frequency (7, 5x/w or every other day) (Exp. 1, stiffness Ovx: 118+13 N/mm, Ovx PTH: 250+/-20 N/mm) being more effective in healthy rats (Exp. 3, stiffness improvement Healthy: 59 to 174 N/mm, Ovx: 52 to 98 N/mm). Serum Oc level was elevated in PTH treated rats. Application from day 14 proved to be less effective (Exp. 3). PTH had no effect (P>0.05) on body, uterus and muscle weight, muscle fiber size, MRA and expression of bone markers. PTH promoted bone healing in Ovx and healthy rats, when it is applied during early stage of healing without having any adverse systemic effect. In perspective, PTH may represent a treatment for enhancement of fracture healing. The findings need to be confirmed by follow-up studies on other animals.
进行了三项实验，以研究甲状旁腺激素（PTH）（1-34）在不同方案下间歇性给药对健康和去卵巢（3 个月大时 Ovx）大鼠骨折愈合和肌肉的影响。5 个月大的大鼠接受双侧胫骨骨干横断切开术，并分为组（每组 12 只大鼠）。在实验 1 中，Ovx 大鼠接受 PTH（7x/w，1-35d）治疗，或接受口服雌二醇-17β-苯甲酸酯（0.4 mg/kg BW，1-35d）治疗，或未治疗。在实验 2 中，有 3 组：健康未治疗或接受 PTH（5x/w，1-35d 或 7-35d）治疗。在实验 3 中，有 7 组：健康、Ovx、“健康 PTH 5x/w 7-35d”、“Ovx PTH 5x/w 7-35d，14-35d 或 14-28d”、“Ovx PTH 每隔一天 7-35d”。单次 PTH 剂量为 40 μg/kg BW。愈合 35 天后，用计算机断层扫描、生物力学、组织学分析对一只胫骨进行分析。另一只胫骨用于分析 Alp、Oc、Trap 1、Igf-1、Rankl、Opg 基因（实验 2、3）。测量血清 Oc 和 Alp。记录体重、子宫重量。分析实验 2 中 M. gastrocnemius 的重量，分析实验 3 中纤维大小和线粒体呼吸活性（MRA）。雌激素增加了子宫重量，防止了体重增加，但并未改善 Ovx 大鼠的骨愈合（实验 1）。从第 1 天和第 7 天开始给予 PTH 可改善所有大鼠的骨参数，而与应用频率（7、5x/w 或每隔一天）无关（实验 1，刚度 Ovx：118+13 N/mm，Ovx PTH：250+/-20 N/mm），在健康大鼠中更有效（实验 3，刚度改善健康：59 至 174 N/mm，Ovx：52 至 98 N/mm）。PTH 治疗的大鼠血清 Oc 水平升高。从第 14 天开始应用被证明效果较差（实验 3）。PTH 对体重、子宫和肌肉重量、肌肉纤维大小、MRA 和骨标志物的表达没有影响（P>0.05）。PTH 促进了 Ovx 和健康大鼠的骨折愈合，当它在愈合早期应用而没有任何全身不良反应时。从前景来看，PTH 可能代表一种增强骨折愈合的治疗方法。这些发现需要通过对其他动物的后续研究来证实。
