Division of Bioengineering, National University of Singapore, Singapore.
Bone. 2011 May 1;48(5):1154-63. doi: 10.1016/j.bone.2011.02.007. Epub 2011 Feb 18.
Osteoporosis remains a challenging problem. Understanding the regulation on osteoclast and osteoblast by drugs has been of great interest. Both anabolic and anti-resorptive drugs yield positive results in the treatment of osteoporosis. However, whether the concurrent administration of parathyroid hormone (1-34) and ibandronate may offer an advantage over monotherapy is still unknown. This study, therefore, attempts to compare the efficacy of two therapeutical approaches and to investigate the beneficial effects in concurrent therapy in a rat model using three-point bending, pQCT and μCT analysis. A total of 60 female Sprague-Dawley rats of age 10 to 12 weeks were divided into 5 groups (SHAM, OVX+VEH, OVX+PTH, OVX+IBAN, OVX+PTH+IBAN) and subjected to ovariectomy or sham surgery accordingly. Low-dose parathyroid hormone (PTH) and/or ibandronate or its vehicle were administered subcutaneously to the respective groups starting from 4th week post-surgery at weekly intervals. Three rats from each group were euthanized every 2 weeks and their tibiae were harvested. The tibiae were subjected to metaphyseal three-point bending, pQCT and μCT analysis. Serum biomarkers for both bone formation (P1NP) and resorption (CTX) were studied. A total of 11 indices showed a significant difference between SHAM and OVX+VEH groups, suggesting the successful establishment of osteoporosis in the rat model. Compared to the previous studies which showed impedance from bisphosphonates in combination therapy with PTH, our study revealed that ibandronate does not block the anabolic effects of PTH in ovariectomized rat tibiae. Maximum load, strength-strain indices and serum bone formation markers of OVX+PTH+IBAN group are significantly higher than both monotherapy groups. With the proper ratio of anabolic and anti-resorptive drugs, the effect could be more pronounced.
骨质疏松症仍然是一个具有挑战性的问题。了解药物对破骨细胞和成骨细胞的调节作用一直是人们关注的焦点。促合成代谢和抗吸收药物在骨质疏松症的治疗中均取得了良好的效果。然而,甲状旁腺激素(1-34)和伊班膦酸盐联合给药是否优于单一疗法仍不清楚。因此,本研究试图比较两种治疗方法的疗效,并通过三点弯曲、pQCT 和 μCT 分析,在大鼠模型中研究联合治疗的有益作用。
共 60 只 10-12 周龄的雌性 Sprague-Dawley 大鼠分为 5 组(SHAM、OVX+VEH、OVX+PTH、OVX+IBAN 和 OVX+PTH+IBAN),并分别进行卵巢切除术或假手术。从术后第 4 周开始,每周一次给予低剂量甲状旁腺激素(PTH)和/或伊班膦酸盐或其载体皮下给药。每组各有 3 只大鼠每隔 2 周处死,取其胫骨。对胫骨进行骺板三点弯曲、pQCT 和 μCT 分析。研究了两种骨形成(P1NP)和骨吸收(CTX)的血清生物标志物。SHAM 和 OVX+VEH 组之间有 11 个指标差异有统计学意义,表明成功建立了大鼠骨质疏松模型。与之前的研究表明双膦酸盐联合 PTH 治疗会产生阻抗不同,我们的研究表明,伊班膦酸盐不会阻断 PTH 对去卵巢大鼠胫骨的促合成代谢作用。与单药治疗组相比,OVX+PTH+IBAN 组的最大载荷、强度-应变指数和血清骨形成标志物显著升高。适当的促合成代谢和抗吸收药物比例,可能会产生更显著的效果。