鲑鱼降钙素对人工髋关节置换后假体使用寿命影响的研究

发布时间：2018-05-26 15:05

本文选题：骨质疏松症 + 全髋置换　；参考：《长江大学》2015年硕士论文

【摘要】：我国现已经进入老龄化阶段,平均寿命的增长使得越来越多患有股骨头坏死或意外性股骨颈骨折的老年人选择人工髋关节假体置换手术以提高生活质量。自本世纪30年代开始由Charnley首次应用全髋关节置换术应用于临床以后,逐渐成为重建关节功能的主要手段。随之手术量的逐渐增加及应用范围的扩大,术后并发症也逐渐显露出来,其中以置换后假体的无菌性松动最常见,成为困扰医生和患者的难题,进而最终导致假体在使用期限内的二次或多次翻修。因此,对人工关节无菌性松动原因和机制的研究,依此探讨可行的预防和治疗方案,使假体寿命延长成为迫在眉睫的技术方向。近几年很多学者的研究已证实,人工关节假体无菌性松动诱导原因包括磨屑颗粒、微动、应力遮挡以及外界因素的介入如工作环境、自身体重、关节腔高液体压力等,其中最重要的因素就是磨屑颗粒所诱导。大多数学者研究认为,巨噬细胞、成纤维细胞、异物巨细胞、成骨细胞等在磨屑颗粒的刺激下产生能诱导破骨细胞生产的骨吸收因子,如：肿瘤坏死因子-α(TOF-α)、白细胞介素-1(IL-1)和白细胞介素-6(IL-6)等可直接增强破骨细胞的骨吸收能力,使人工关节置换周围的骨发生溶解或吸收,假体与骨之间微动产生松动。综上可知,破骨细胞的数量增多及功能异常,直接影响到假体与骨之间的稳定性,致使周围骨组织骨溶解吸收,最终导致人工关节置换手术的失败。若以此推理,我们不难得知,通过抑制破骨细胞的活性,减少破骨细胞的数量来积极延缓或抑制骨溶解或骨吸收,是否能延长置换后假体使用寿命呢?鲑鱼降钙素作用的源头就在于破骨细胞。通过对其临床中治疗骨质疏松患者的过程中可证实,药理剂量的鲑鱼降钙素能够完全抑制破骨细胞的骨吸收,并且破骨细胞数量也明显下降,从而降低骨量丢失。本课题拟以此为出发点,通过对降钙素及其特异性受体的研究,进行如下相关研究,为临床提高人工关节置换术后假体使用寿命提供实验依据。本次课题研究中主要包括以下三个内容：1.骨质疏松症患者全髋置换中应用鲑鱼降钙素治疗后影响假体翻修的分析2.磨屑颗粒诱导假体松动的动物实验研究3.鲑鱼降钙素与人工关节无菌性松动的相关性研究第一部分：骨质疏松症患者全髋置换中应用鲑鱼降钙素治疗后影响假体翻修的分析目的：回顾性分析5年内骨质疏松患者接受初次全髋置换术后应用鲑鱼降钙素对于假体二次翻修的影响,探讨初次全髋置换术后应用鲑鱼降钙素与假体的临床使用寿命之间的可能存在的相关性。方法：随机选取作者所在实习医院(荆州市中心医院)病例科2010年-2015年间行人工髋关节置换术患者病例500例552髋(病种不限),其中存在骨质疏松症病例126例(检索过程中存在双髋关节置换患者从总病例数中已扣除)；将目标样本以二次翻修为条件进行筛选后,可检索出43例因不同原因接受二次翻修,其中将17例患者在初次换髋术后应用鲑鱼降钙素的骨质疏松患者拟为A组；在剩余26例中随机抽取17例为B组进行临床对照。将A、B两组数据分别查阅患者假体类型、年龄、性别、初次换髋时间至翻修时间(手术部位不分左右),采用SPSS17.0统计学软件对数据进行分析,骨质疏松症患者中鲑鱼降钙素治疗组与非治疗组患者假体翻修率,以P0.05表示差异具有统计学意义。结果：A组中患者年龄阶段为72-84岁,平均年龄76.8岁；男性6例,女性11例；B组年龄56-82岁,平均年龄68.6岁；男性8例,女性9例,比较差异不具有统计学意义(P0.05)。A组初次换髋时间至翻修时间最短时间26个月,最长时间49个月,平均35.7个月；B组最短时间为14个月,最长时间33个月,平均23.5个月,比较差异具有统计学意义(P0.05)结论：目前鲑鱼降钙素已经是治疗骨质疏松症的常见药物之一,在治疗OP的过程中也抑制破骨细胞的形成,进而可降低假体周围骨溶解,使假体与骨之间不能轻易产生微动或下沉,进而提高假体使用寿命。样本以二次翻修为条件进行筛选后,可检索出43例因不同原因接受二次翻修,其中将17例患者在初次换髋术后应用鲑鱼降钙素的骨质疏松患者拟为A组；在剩余26例中随机抽取17例为B组进行临床对照。将A、B两组数据分别查阅患者假体类型、年龄、性别、初次换髋时间至翻修时间(手术部位不分左右),采用SPSS17.0统计学软件对数据进行分析,骨质疏松症患者中鲑鱼降钙素治疗组与非治疗组患者假体翻修率,以P0.05表示差异具有统计学意义。结果：A组中患者年龄阶段为72-84岁,平均年龄76.8岁；男性6例,女性11例；B组年龄56-82岁,平均年龄68.6岁；男性8例,女性9例,比较差异不具有统计学意义(P0.05)。A组初次换髋时间至翻修时间最短时间26个月,最长时间49个月,平均35.7个月；B组最短时间为14个月,最长时间33个月,平均23.5个月,比较差异具有统计学意义(P0.05)结论：目前鲑鱼降钙素已经是治疗骨质疏松症的常见药物之一,在治疗OP的过程中也抑制破骨细胞的形成,进而可降低假体周围骨溶解,使假体与骨之间不能轻易产生微动或下沉,进而提高假体使用寿命。第二部分：磨屑颗粒诱导假体松动的动物实验研究目的：通过对磨屑颗粒诱导假体无菌性松动的机制的理解下制作动物模型,并取假体周围骨及界膜组织进行研究分析,探讨磨屑颗粒对假体-骨间骨量变化、破骨细胞变化及其组织形态的影响。方法：采用无菌健康成年新西兰大白兔12只(由湖北中医药高等专科学校实验动物中心提供并饲养),体重23±0.4 Kg,雌雄不限。随机平均分为实验组和对照组且均选取左侧髋关节为实验部位。实验组在术后4周每次向关节腔无菌注射磨屑颗粒混合液0.5ml,对照组无菌注射生理盐水0.5ml,直至术后16周后检测假体周围感应区骨密度(BMD)变化。术后满16周后处死两组实验动物,取假体周围组织行大体及光学显微镜下观察、细菌培养、并做放免法测定TNF-α、IL-6含量。结果：假体四周感应区BMD的改变中实验组明显下降,两组间有显著性差异升高(P0.05),且实验组组间对比可见随着时间的推移,直至16周后比较术前BMD有显著性差异(P0.01)。对照组BMD未见明显改变,同组内对比结果无统计学差异(P0.05)。大体观察钛合金假体周围情况,实验组的假体周围包裹了一层纤维样组织膜；而对照组没有这样类似的纤维膜,而紧贴骨组织或有一层新生骨组织包裹。细菌培养结果可见两组均表现为阴性。放免检测可见实验组组织中的TNF-α、IL-6含量均明显高于对照组,具有统计学差异(P0.05)有意义。结论：本次动物模型的制作基本相似于临床上人工关节置换后假体无菌性松动的衬性骨溶解。由此推理,磨屑颗粒就是导致人工髋关节置换后假体周围骨量丢失及增加破骨细胞数目的主要因素。最终以假体周围骨质破坏、假体松动为临床表现,迫使其使用寿命缩短。第三部分：鲑鱼降钙素与人工关节无菌性松动的相关性研究目的：实验性研究治疗骨质疏松药物鲑鱼降钙素对于全髋关节置换术后假体松动的预防作用,并探讨其在临床中应用的可能性分析。方法：选取健康成年且在无菌条件下饲养的新西兰大白兔18只(由湖北中医药高等专科学校实验动物中心提供并饲养)；体重2.3±0.4 Kg,雌雄不限。分别为药物实验组、动模对照组及空白生理盐水对照组,并均选取左侧髋关节为实验部位。术后第四周开始,分别于术后第4、6、8、10、12、14周向药物实验组及动模对照组的兔左髋关节腔在无菌的条件下注射磨屑颗粒混合悬液(钛合金及聚乙烯颗粒),空白生理盐水对照组注射生理盐水均为每次1ml,每2周一次,直至术后14周。术后第二周开始向药物实验组大白兔的手术侧关节囊内注射降钙素1ml,每3天一次,直到第16周。同时其余两组大白兔的手术侧关节囊内注射生理盐水lml,同样每3天一次,直至第16周。三组大白兔在试验周内每日喂养含有钙尔奇药物成分的食物。采取大体观察、假体周围细菌培养、光学显微镜下观察假体周围组织形态改变,并检测假体周围感应区骨密度(BMD)、放免法测定TNF-α、IL-6含量。结果：大体观察：将动物处死后手术取出模拟人工假体后,可见药物实验组及生理盐水对照组人工假体周围骨小梁较为完整,动模对照组人工假体周围包裹了一层纤维样组织,骨小梁较药物组明显破坏。药物实验组与空白生理盐水对照组组间对比无明显差异。细菌培养结果可见三组.均表现为阴性。药物实验组界膜组织表现为成熟的骨组织、少量的纤维结缔组织或有新生骨形成,未见明显的组织细胞反应。动模对照组人工假体周围产生一层含有大量的巨噬细胞和异物巨细胞的纤维结缔组织界膜。生理盐水对照组由于手术过程中破坏周围组织可见轻度创伤性炎症改变。药物治疗组在介入鲑鱼降钙素治疗后,假体周围骨量较单纯动物模型组丢失明显减少,两者之间存在差异(P0.05),具有统计学意义；两组对照组经过对比,可见磨屑颗粒动物模型组骨量丢失明显比生理盐水空白对照组高,两者之间存在明显差异(P0.01),具有统计学意义；药物治疗组与空白生理盐水对照组之间,在短期内(8周以内)骨量丢失量无明显差异(P0.05)；但在8周以后可见鲑鱼降钙素治疗组骨量丢失相对较多,两者存在差异(P0.05)。具有统计学意义。结果经统计显示药物治疗组的组织中TNF-α及IL-6含量明显低于动物模型对照组,具有统计学差异(P0.05)有意义。两组对照组之间可见动物模型组中TNF-α及IL-6含量明显升高,两者存在显著差异(P0.01),具有统计学意义。而药物治疗组与生理盐水对照组中的TNF-α及IL-6含量差异性不明显,(P0.05),不具有统计学意义。结论：鲑鱼降钙素能够通过影响破骨细胞活性,促使破骨细胞的数量骤减,从而使磨屑颗粒诱导下的骨溶解机制减慢,间接性的提高人工关节置换假体与骨之间的寿命。
[Abstract]:Our country is now entering the aging stage. The growth of average life expectancy makes more and more elderly people with femoral head necrosis or accidental femoral neck fracture to choose artificial hip prosthesis replacement to improve the quality of life. Since 30s this century, the first application of total hip arthroplasty by Charnley was gradually applied to the clinic. As the main means of reconstruction of joint function. With the gradual increase of the amount of operation and the expansion of the scope of application, postoperative complications are gradually revealed. Among them, the most common aseptic loosening of prostheses after replacement has become a difficult problem for doctors and patients, which eventually leads to the two or multiple refurbishment of the prosthesis in the duration of use. Research on the causes and mechanisms of aseptic loosening of the joints is studied, and the feasible prevention and treatment scheme is discussed, and the life span of the prosthesis has become an urgent technical direction. In recent years, many scholars have confirmed that the causes of aseptic loosening of artificial joint prosthesis include debris particles, micromovement, stress shielding, and external factors intervention. The most important factor, such as working environment, body weight, high fluid pressure in the joint cavity, is the induction of debris particles. Most scholars have considered that macrophages, fibroblasts, foreign body giant cells, osteoblasts, and so on produce bone resorption factors that can induce osteoclast production under the stimulation of debris particles, such as the cause of the tumor's bad death Sub - alpha (TOF- - alpha), interleukin -1 (IL-1) and interleukin -6 (IL-6) can directly enhance the bone resorption of osteoclasts, dissolve or absorb the bone around the replacement of the prosthesis, and the movement between the prosthesis and the bone leads to the loosening of the bone. It is known that the number of osteoclasts and the abnormal function are directly affected by the prosthesis and bone. Stability, resulting in the absorption of osteolysis around the bone tissue and the failure of artificial joint replacement surgery. In this case, it is not difficult to know whether to postpone or inhibit osteolysis or bone resorption by inhibiting the activity of osteoclasts, reducing the number of osteoclasts, and prolonging the life of the prosthesis after replacement? Salmon calcitonin The source of the use is osteoclast. Through the treatment of patients with osteoporosis in clinical treatment, it is proved that the pharmacological dose of salmon calcitonin can completely inhibit bone resorption of osteoclast and decrease the number of osteoclasts, thus reducing the loss of bone mass. The study of heterosexual receptors is conducted to provide an experimental basis for clinical improvement of the life span of prosthesis prosthesis. In this study, the following three contents are included: 1. analysis of the effect of salmon calcitonin in the total hip replacement of osteoporosis patients and the analysis of prosthesis refurbishment after the use of salmon calcitonin, 2. debris induced prosthesis A study of the relationship between 3. salmon calcitonin and aseptic loosening of artificial joints. Part 1: analysis of the effects of salmon calcitonin in total hip replacement for osteoporosis patients affecting prosthesis revision: retrospective analysis of the use of salmon calcitonin for 5 years after primary total hip replacement for patients with osteoporosis The possible correlation between the clinical service life of salmon calcitonin and prosthesis after primary total hip replacement was investigated in the effect of two refurbishment of prostheses. Methods: randomly selected 500 cases of 552 hip arthroplasty cases in the case Department of the author's Hospital (Jingzhou Central Hospital) in -2015 in 2010 (500 cases of hip arthroplasty). There are 126 cases of osteoporosis in which there are 126 cases of osteoporosis (double hip replacement patients have been deducted from the total number of cases). After screening the target samples with two refurbishment conditions, 43 cases can be retrieved for two refurbishment for different reasons, of which 17 patients are used for salmon calcitonin after the first hip replacement. The patients with osteoporosis were intended to be A group; 17 of the remaining 26 cases were randomly selected as group B for clinical control. The data of A and B two groups were examined for the type of prosthesis, age, sex, the first hip change time to the refurbishment time (the surgical site was not about), the data were analyzed with the SPSS17.0 statistics software, and the salmon in the osteoporosis patients. The prosthesis revision rate in the calcitonin treatment group and the non treatment group was statistically significant by P0.05. Results: the age of the patients in the A group was 72-84 years old, the average age was 76.8 years, 6 men and 11 women, the B group was 56-82 years old, the average age was 68.6 years, the male 8 cases and the female 9 cases were not statistically significant (P0.05).A. The shortest time for the first time to change the hip to the refurbishment time is 26 months, the longest time is 49 months, an average of 35.7 months. The shortest time of group B is 14 months, the longest time is 33 months, the average is 23.5 months, the difference is statistically significant (P0.05) conclusion: salmon calcitonin is one of the common drugs for the treatment of osteoporosis, and is in the treatment of OP In the process, the formation of osteoclast is inhibited, and the osteolysis around the prosthesis can be reduced, and the prosthesis and bone can not be freed or sink easily, and then the life span of the prosthesis is improved. After screening the samples with two refurbishment conditions, 43 cases can be retrieved for two refurbishment for different reasons, of which 17 patients are changed to the hip for the first time. The osteoporosis patients with salmon calcitonin were planned to be A group, and 17 of the remaining 26 cases were randomly selected as B group for clinical control. The data of A and B two groups were examined for the type of prosthesis, age, sex, the first time of hip replacement and the time of revision (the surgical site was not divided), and the data were analyzed by SPSS17.0 statistics software. The rate of prosthesis revision in the salmon calcitonin treatment group and the non treatment group was statistically significant by P0.05. Results: the age of the patients in the A group was 72-84 years, the average age was 76.8 years, 6 men and 11 women, the B group was 56-82 years old, the average age was 68.6 years, 8 men and 9 women. Statistical significance (P0.05) group.A first time for the first time to change the hip time to the shortest time 26 months, the longest time of 49 months, an average of 35.7 months, the shortest time in group B is 14 months, the longest time 33 months, the average 23.5 months, the difference is statistically significant (P0.05) conclusion: salmon calcitonin is now a common drug for the treatment of osteoporosis One of them also inhibits the formation of osteoclasts during the treatment of OP, and then reduces osteolysis around the prosthesis, so that the prosthesis and bone can not easily produce fretting or sinking, and thus the life of the prosthesis is improved. The second part: Animal Experimental Study of debris particles induced prosthesis loosening by abrasive particles: no prosthesis induced by debris particles Under the understanding of the mechanism of bacterial loosening, the animal model was made, and the periprosthetic bone and boundary membrane tissues were studied. The effects of debris particles on the changes of bone mass, osteoclast and tissue morphology were investigated. Methods: 12 New Zealand white rabbits were used in aseptic healthy adult New Zealand (Hubei College of Chinese Medicine experiment). The animal center was provided and raised with a weight of 23 + 0.4 Kg and male and female. The experimental group was randomly divided into the experimental group and the control group. The left hip joint was selected as the experimental site. The experimental group was injected with the mixture of debris particles 0.5ml to the articular cavity 4 weeks after the operation, and the control group was aseptic injected with the physiological saline 0.5ml until 16 weeks after the operation to detect the periprosthesis. The bone mineral density (BMD) changes in the induction area. After 16 weeks after operation, two groups of experimental animals were killed. The tissues around the prosthesis were observed under the microscope, the bacteria culture and the radioimmunoassay were used to determine the TNF- alpha and IL-6 content. Results: the experimental group decreased significantly in the BMD changes around the prosthesis, and there was a significant difference between the two groups (P0.05), and the experiment The comparison between group groups showed that there were significant differences in BMD before 16 weeks (P0.01). There was no significant change in BMD in the control group, and there was no significant difference between the same group (P0.05). The periprosthesis of the experimental group was wrapped around a fibrous tissue membrane around the prosthesis in the experimental group; and the control group did not have this Similar fibrous membrane, and clingy bone tissue or a layer of new bone tissue wrapped. Bacterial culture results showed that the two groups were negative. The radioimmunoassay showed that the content of TNF- alpha in the experimental group was significantly higher than that of the control group. The statistical difference (P0.05) was significant. Conclusion: the animal model was basically similar to the clinical model. Aseptic osteolysis of aseptic loosening of prosthesis after replacement of prosthesis. It is concluded that debris is the main factor leading to the loss of bone mass around the prosthesis and the increase of the number of osteoclasts after the replacement of the hip prosthesis. The final bone destruction around the prosthesis, the prosthesis loosening is the clinical manifestation, and the life span is shortened. Third parts: A study on the correlation between salmon calcitonin and aseptic loosening of artificial joints: an experimental study on the preventive effect of salmon calcitonin on prosthesis loosening after total hip replacement and the possibility analysis of its clinical application. 18 rabbits (provided and fed by experimental animal center of Hubei College of Chinese Medicine); weight 2.3 + 0.4 Kg, male and female, and male and female. They were the experimental group, the dynamic model control group and the blank saline control group, and the left hip joint was selected as the experimental site. Fourth weeks after the operation, the drug was given to the drug after the operation, respectively. The left hip joint cavity of the rabbits in the experimental group and the dynamic model control group was injected with abrasive particles mixed suspension (titanium alloy and polyethylene) under aseptic conditions. The blank saline control group was injected with 1ml each time, once every 2 weeks, until 14 weeks after the operation. The operation side of the experimental group began to be injected into the operation side of the experimental group of rabbits at second weeks. Calcitonin 1ml, once every 3 days, until sixteenth weeks. At the same time, the other two groups of rabbits were injected with saline LML in the surgical side of the joint capsule, once every 3 days, and until sixteenth weeks. The three groups of rabbits fed the calchic ingredients daily within the test week. The changes of tissue morphology around the prosthesis were observed and the bone mineral density (BMD) around the induction area around the prosthesis was detected, and the radioimmunoassay was used to determine the TNF- alpha and IL-6 content. Results: general observation: after the animal was executed, the simulated prosthesis was removed, and the bone trabecula around the artificial body of the drug experiment group and the saline control group was more complete, and the dynamic model control group was artificial false. A layer of fibrous tissue was wrapped around the body, and the bone trabecula was significantly damaged than the drug group. There was no significant difference between the drug experiment group and the blank saline control group. The results of the bacterial culture showed that the three groups were negative. The membrane tissue of the drug experiment group showed mature bone tissue, a small amount of fibrous connective tissue or new bone shape. A layer of fibrous connective tissue boundary membrane containing a large number of macrophages and foreign body giant cells was produced around the prosthesis in the control group. In the saline control group, mild traumatic inflammation was seen in the surrounding tissue during the operation. The drug treatment group was treated with salmon calcitonin treatment in the drug treatment group. The bone mass around the prosthesis was significantly less than that of the simple animal model group, and there was a significant difference between the two groups (P0.05). The comparison between the two groups showed that the bone mass loss of the animal model group was significantly higher than that of the normal saline blank control group, and there was a significant difference between the two groups (P0.01), with statistical significance. There was no significant difference in bone mass loss between the treatment group and the blank control group (P0.05) in the short term (P0.05), but the bone loss in the salmon calcitonin group was relatively large after 8 weeks, and there was a difference between the two groups (P0.05). The statistical significance was statistically significant. The results showed that the content of TNF- alpha and IL-6 in the tissue of the drug treatment group was clear. Significantly lower than the animal model control group, with statistical difference (P0.05) significant. Between the two groups of control, TNF- and IL-6 contained in the animal model group.
【学位授予单位】：长江大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R687.4

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