Bisphosphonates suppress periosteal osteoblast activity independently of resorption in rat femur and tibia
Bisphosphonates suppress periosteal osteoblast activity independently of resorption in rat femur and tibia
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DOI：
10.1016/j.bone.2006.05.006
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发表时间：
2006-11-01
期刊：
影响因子：
4.1
通讯作者：
Burr, David B.
中科院分区：
文献类型：
--
作者：
Iwata, Ken;Li, Jiliang;Burr, David B.
最近的研究表明，双膦酸盐通过导致破骨细胞凋亡和抑制向成熟破骨细胞的分化来抑制骨吸收。双膦酸盐对骨形成的影响尚不清楚，尽管已经假设双膦酸盐在体外抑制成骨细胞凋亡并刺激成骨细胞增殖和分化，导致骨形成增加。本研究的目的是研究双膦酸盐对骨形成的影响。我们给6个月大的雌性Sprague-Dawley大鼠皮下注射0.05、0.5或5.0 μ g/kg/天的利塞膦酸盐或0.1、1.0或10 μ g/kg/天的阿仑膦酸盐17天。对照组大鼠每天皮下注射生理盐水。处死后，收获股骨和胫骨中段骨干，测量骨膜和皮质内表面的矿化表面（MS/BS）、矿物质沉积率（MAR）和骨形成率（BFR/BS）。在股骨中，所有治疗组的骨膜MAR均显著低于对照组（利塞膦酸钠组为22-29%，阿仑膦酸钠组为26-36%）。在胫骨中，所有治疗组的骨膜MAR和BFR均显著低于对照组（利塞膦酸钠组为41-50%，阿仑膦酸钠组为43-52%）。由于这些骨的骨膜表面仅在建模模式下进行骨形成，我们的研究结果表明，双膦酸盐抑制骨形成独立的骨吸收。因为这种作用是在骨膜MAR上而不是在骨膜MS/BS上观察到的，我们假设双膦酸盐在细胞水平上影响单个成骨细胞的活性。这可能有助于解释特立哌酮的合成代谢作用在人体中与双膦酸盐同时给药或在双膦酸盐疗程后给药时减弱的原因。(C)2006年爱思唯尔公司All rights reserved.
Recent studies demonstrate that bisphosphonates suppress bone resorption by leading to apoptosis of the osteoclast and inhibiting the differentiation to mature osteoclasts. The influence of bisphosphonates on bone formation is unknown, although it has been hypothesized that bisphosphonates inhibit osteoblast apoptosis and stimulate osteoblast proliferation and differentiation in vitro, leading to increased bone formation. The purpose of this study was to investigate the effect of bisphosphonates on bone formation. We administered risedronate at 0.05, 0.5 or 5.0 mu g/kg/day or alendronate at 0.1, 1.0 or 10 mu g/kg/day subcutaneously for 17 days to 6-month-old female Sprague-Dawley rats. Control rats were given a daily subcutaneous injection of saline. Following sacrifice, the femoral and tibial mid-diaphyses were harvested and mineralizing surface (MS/BS), mineral apposition rate (MAR) and bone formation rate (BFR/BS) were measured on periosteal and endocortical surfaces. In the femur, periosteal MAR was significantly lower in all treatment groups (22-29% for risedronate, 26-36% for alendronate) than in control. In the tibia, periosteal MAR and BFR of all treatment groups were significantly lower (41-50% for risedronate, 43-52% for alendronate) than in the control group. Because the periosteal surfaces of these bones are only undergoing bone formation in modeling mode, our results show that bisphosphonates suppress bone formation independently of bone resorption. Because this effect is seen on periosteal MAR rather than on periosteal MS/BS, we hypothesize that bisphosphonates affect the activity of individual osteoblasts at the cell level. This may help to explain the reason that the anabolic effects of teriparatide are blunted when administered concurrently with or following a course of bisphosphonates in humans. (C) 2006 Elsevier Inc. All rights reserved.