Drescher Wolf, Li Haisheng, Jensen Søren D, Ingerslev Jørgen, Hansen Ebbe S, Hauge Ellen M, Bünger Cody
Department of Orthopaedics, Aarhus University Hospital, Denmark.
J Orthop Res. 2002 Jul;20(4):662-8. doi: 10.1016/S0736-0266(01)00183-8.
The effect of long term steroid treatment on coagulation, intraosseous pressure (IOP), femoral head (FH) blood flow, and histology in the normal organism was investigated in this study in growing pigs. From 24 growing female Danish Landrace pigs from 12 litters, 12 animals daily received 100 mg methylprednisolone orally for three months. Their 12 sister pigs served as controls without steroid treatment. Prothrombin time, activated partial thromboplastin time (aPTT), fibrinogen, and antithrombin III levels were recorded in jugular venous blood. Blood flow of the hip regions was measured by means of the radioactive microsphere technique. Metaphyseal and epiphyseal IOP of the left or right proximal femur were measured. Histomorphometry of the left or right FH epiphysis was performed. Major growth inhibition was found in the corticosteroid (CS) treated group. In CS pigs, aPTT was shortened to 50% compared to control pigs. Plasma fibrinogen was higher in the CS animals. Total FH blood flow was not different while regional blood flow in the cranial subregion of the FH epiphysis was higher in the CS group. Metaphyseal and epiphyseal IOP of the proximal femur were not different in the CS animals. Histomorphometrically, cancellous bone volume (23 +/- 1% vs. 34 +/- 2%; p < 0.001) and bone turnover (10 +/- 2% vs. 55 +/- 8%; p < 0.001) of the FH epiphysis was lowerin the CS than in the control group. The FH epiphysis of the CS animals invariably showed an irregular cartilage-bone interface with cartilaginous projections into the subchondral bone mainly in its cranial part. In normal growing pigs, long term high dose CS treatment has induced a hypercoagulable state of plasma via the intrinsic pathway of coagulation, cartilaginous projections into FH subchondral bone, FH osteopenia, and reduced bone turnover. Long-term steroid treatment did not produce FH necrosis or FH IOP alterations in the immature pig model.
本研究在生长猪中探究了长期类固醇治疗对正常机体凝血、骨内压(IOP)、股骨头(FH)血流及组织学的影响。从12窝24只生长中的雌性丹麦长白猪中,12只动物每天口服100mg甲泼尼龙,持续三个月。它们的12只姐妹猪作为未接受类固醇治疗的对照。记录颈静脉血中的凝血酶原时间、活化部分凝血活酶时间(aPTT)、纤维蛋白原和抗凝血酶III水平。通过放射性微球技术测量髋部区域的血流。测量左或右近端股骨的干骺端和骨骺端IOP。对左或右FH骨骺进行组织形态计量学分析。在皮质类固醇(CS)治疗组中发现了主要的生长抑制。与对照猪相比,CS猪的aPTT缩短至50%。CS动物的血浆纤维蛋白原更高。FH总血流量无差异,而CS组中FH骨骺颅侧亚区域的局部血流量更高。CS动物近端股骨的干骺端和骨骺端IOP无差异。组织形态计量学显示,CS组FH骨骺的松质骨体积(23±1%对34±2%;p<0.001)和骨转换(10±2%对55±8%;p<0.001)低于对照组。CS动物的FH骨骺总是显示出不规则的软骨-骨界面,软骨突起主要进入其颅侧部分的软骨下骨。在正常生长的猪中,长期高剂量CS治疗通过凝血的内源性途径、FH软骨下骨的软骨突起、FH骨质减少和骨转换降低诱导了血浆的高凝状态。长期类固醇治疗在未成熟猪模型中未产生FH坏死或FH IOP改变。