Aspenberg Per, Wermelin Karin, Tengwall Pentti, Fahlgren Anna
Section of Orthopedics, Department of Neuroscience and Locomotion, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
Acta Orthop. 2008 Feb;79(1):111-5. doi: 10.1080/17453670710014851.
When PTH is used to increase the amount of bone in osteoporotic patients, combination with bisphosphonates is known to attenuate the response. This might be explained by the reduced number of remodeling sites after bisphosphonate treatment, which reduces the number of cells able to respond to PTH. However, in a repair situation after trauma, a large number of osteoblasts reside in the wound site. If their activity is no longer coupled to osteoclasts, decreased resorption by bisphosphonates and stimulation of osteoblastic activity by PTH should both (independently) increase bone formation. Thus, we hypothesized that in contrast to the case in osteoporosis treatment, PTH and bisphosphonates have an additive effect in situations involving bone regeneration.
Stainless steel screws, either coated with biphosphonates or uncoated, were inserted in 46 rat tibias. This normally elicits a bone repair response, leading to a gradual increase in the strength of screw fixation. Half of the rats also received daily injections of teriparatide (PTH). Thus, there were 4 groups: control, bisphosphonate, PTH, and bisphosphonate plus PTH. Pull-out force and energy were measured after 2 weeks.
The combined treatment had the strongest effect. It doubled the pull-out force and tripled the pull-out energy, compared to untreated controls. Also, bisphosphonate or PTH alone increased the pull-out force and energy, although less. No treatment cross-dependency was observed.
Because bisphosphonates mainly influence osteoclasts, and intermittent administration of PTH mainly influences osteoblasts, our findings indicate that to a large extent these cells work without coupling in this model. It appears that bisphosphonates are unlikely to attenuate the response to PTH during the formation of new bone.
当使用甲状旁腺激素（PTH）增加骨质疏松患者的骨量时，已知与双膦酸盐联合使用会减弱反应。这可能是由于双膦酸盐治疗后重塑部位数量减少，从而减少了能够对PTH作出反应的细胞数量。然而，在创伤后的修复情况下，大量成骨细胞存在于伤口部位。如果它们的活性不再与破骨细胞耦联，双膦酸盐减少的吸收以及PTH对成骨细胞活性的刺激都应该（独立地）增加骨形成。因此，我们假设与骨质疏松治疗的情况相反，PTH和双膦酸盐在涉及骨再生的情况下具有相加作用。
将涂有或未涂有双膦酸盐的不锈钢螺钉插入46只大鼠的胫骨中。这通常会引发骨修复反应，导致螺钉固定强度逐渐增加。一半的大鼠还每天接受特立帕肽（PTH）注射。因此，有4组：对照组、双膦酸盐组、PTH组和双膦酸盐加PTH组。2周后测量拔出力和能量。
联合治疗效果最强。与未治疗的对照组相比，拔出力增加了一倍，拔出能量增加了两倍。此外，单独使用双膦酸盐或PTH也增加了拔出力和能量，尽管增加幅度较小。未观察到治疗交叉依赖性。
由于双膦酸盐主要影响破骨细胞，而间歇性给予PTH主要影响成骨细胞，我们的研究结果表明在该模型中这些细胞在很大程度上是独立工作的。在新骨形成过程中，双膦酸盐似乎不太可能减弱对PTH的反应。
