云克调节绝经后骨质疏松骨代谢调节作用.doc

云克调节绝经后骨质疏松骨代谢调节作用云克对骨组织有良好的靶向性，进入体内后被骨生成区和带有炎症的骨关节和软骨迅速摄取、蓄积。云克在血液中半排期为0.52h，血液中的30%40%迅速分布并最终贮存在骨骼内，半排期可达69月，终端骨半排期在1年以上。对骨代谢调节发挥重要作用。在骨代谢调节过程中IL-1、IL-6、TNF-被认为是骨组织微环境中溶骨细胞因子网络中的关键成员，参与骨代谢影响骨重建。IL-1、IL-6不仅直接刺激骨吸收，还增强其他细胞因子的作用，使骨吸收大大增加。TNF-刺激破骨细胞前体细胞增生分化为成熟的破骨细胞，同时改变骨碱性磷酸酶的（BALP）活性。BALP、BGP在绝经后骨质疏松演变过程中代表由破坏细胞造成骨吸收的、骨形成高转换状态。云克是一种外源性钙代谢调节物质，进入体内以后吸附于骨组织的羟基磷灰石晶体表面，抑制磷酸酶的降解，不仅延缓磷灰石结晶聚集成大块晶体，同时也抑制磷灰石晶体溶解。被破骨细胞摄取，可直接抑制破骨细胞活性，达到抑制骨溶解（骨破坏）、降低血钙、缓解骨痛的作用。云克还通过螯合金属离子降低金属蛋白酶、胶原酶的活性，从而抑制胶原酶对骨组织的破坏。云克中含有人工合成的锝元素，在低价状态下化学性质活泼，容易得到和失去电子，具有清除体内自由基、抑制病理的复合物产生作用、抑制白细胞介素的产生。由此可见云克在骨代谢调节中的作用不仅直接抑制破骨细胞活性，而且具有抑制白细胞介素的产生，降低金属蛋白酶、胶原酶活性的作用。本研究跟踪随访的113例绝经后骨质疏松患者，统计的治疗前后细胞因子、骨代谢指标及BMD的变化与国内的相关报道一致。与李茂良等中国专利说明书论述的药物作用相同。云克的二磷酸盐成分及金属离子锝参与骨代谢，降低IL-1、Il-6、TNF-、BALP、BGP作用确切，并具有增加BMD 的作用。其增加BMD的作用机制是抑制了破骨细胞活性，间接提高了成骨细胞的功能。The regulation of Yunke in bone metabolism of postmenopausal osteoporosisZHANG Mengmeng, LIU Zhonghou, WU naibao, et al.Research Lab of Bone Metabolism, No.4 Hospital of Jilin University, Changchun 130011, ChinaAbstract: Objective Yunke is a kind of multiple preparation with the bisphonate and microelemengt. To study the regulation of Yunke in bone metabolism by following 113 patients with postmenopausal osteoporosis in 9th month after therapy. Method To observe the effects of Yunke on the serum IL-1, IL-6, TNF-, BGP, BALP, E2 and bone mineral density(BMD) in 113 patients with postmenopausal osteoporosis. Result Before medication, BMD and the level of serum E2 significantly decreased (P0.01), And the level of TNF- was high than that in control group (P0.05). The levels of serum IL-1, IL-6, TNF-, BGP, BALP decreased rapidly in the 9th month after therapy. There was no change on the level of serum E2. Conclusion Yunke plays on obvious the activity of osteoclast and the loss of bone, and increase BMD.Key words: postmenopausal osteoporosis; Yunke; Bosorption; Bone metabolism; Bone formationYunke is a chelate composed of methylenediphosphonate and technetium got from which sodium pertechnetate reduced by stannous chloride and methylenediphosphonate. YunKe has the stable P-C-P bond. It can been ingested quickly by bone and the effect is lasting. Besides, its blood clearance rate is high.This paper reported the regulation of YunKe in Bone Metabolism by observing the changes on the level of serum BMD,BALP,BGP,TNF-,IL-1,IL-6,E2 of 113 patients with postmenopausal osteoporosis after therapy.1. Material and method1.1 The treatment observation object According to the case history, sign, bone density measurement and X-ray examination, the 113 patients of 53-75 years old were clearly diagnosed to be postmenopausal osteoporosis and with 5-25 years menopausal histories, while their livers function and kidney function were normal. The 113 patients were all with low back pain, lassitude in the tibia and knee, pain in foot and heel, and 21 patients of them once with fracture history of wrist joint or thoracic vertebrae or lumbar. The control group was 60 patients of 4351 years old examined to be without disease of heart, liver, kidney and endocrine function.1.2 Instruments and examination methodDual Energy X-ray Absorptiometry produced by Osteometer Medi Tech Co.,Ltd, Automatic Microparticle Chemiluminescence Meter produced by Beckman in American, Dual Probe Radioimmunoassay Analyzer produced by Shanghai Nuclear Radiation Institute.The life history, family history, menstrual history, past history, movement quantity, and special medication history of every testee were collected. The serum BMD, BALP, BGP, TNF-,IL-1,IL-6, E2 were examined separately at the time of before treatment, the 3th month and 9th month after treatment.1.3 Method of treatmentPlaced the chelate of preparation A 0.20g and preparation B 20mg of Yunke at room temperature for 510mins, then disluted by adding 250ml of normal saline to chelate adequately, ivgtt. qd, for continuous 15 days as a course of treatment.2 ResultsAfter two weeks of treatment, the back pains and knee ache flabbiness on patients obviously relievied .After one month of theatment, bone pains disappered on 80% patients accounted in their own words. After 3mos callback, indicated that no change on the BMD, while the level of IL-1,IL-6 significantly decreased. The level of BALP also decreased after treatment. After 9mos of treatment the level of serum BALP,BGP,TNF-,IL-1,IL-6 decreased rapidly and no change for the level of serum E2, while BMD increased. Table 1 shows the comparison of serum BALP,BGP,TNF-,IL-1,IL-6,E2 for patients with postmenopausal osteoporosis, and table 2 shows the comparison of BMD before and after treatment for patients with postmenopausal osteoporosis.Table 1 Comparison of the serum BALP,BGP,TNF-,IL-1,IL-6,E2between two group (x s )GroupSubjectsBALP(ng/ml)BGP(ng/ml)TNF-(mg/ml)IL-1(ng/ml)IL-6(ng/ml) E2(ng/ml)Control group605.624.015.012.011.130.970.190.0694.9039.9336.4020.07OP groupPre treatment11317.036.316.031.382.290.830.700.18139.7655.4912.89.55Post treatment1136.445.03*5.261.44*1.240.76*0.310.10*97.7861.04*11.9910.01*: comparison with pre-treatment P0.01Table 2 Comparison of BMD before and after therapyof postmenopausal osteoporosis(x s )GroupSubjects Left cubitus radioLeft cubitus ulna Mean BMDControl group600.6090.1030.6300.1160.6190.120OP groupPre treatment1130.4510.1700.4580.1310.4540.150Post treatment1130.5230.182*0.3590.129*0.5310.155*: comparison with pre-treatment P0.013 DiscussionYunke has strong ability of targeting to bone tissues. When entered in blood system, it can be rapidly taken in and accumulated in the inflamed bone joints and synovial tissues. The elimination half-time of Yunke in blood is 0.52h. The 30%40% Yunke in blood is soon distributed and finally stored in skeletons. The elimination half-time of Yunke in skeletons is 6mo9mo and even more than 1ys. For regulation of bone metabolism Yunke plays important effect.During the regulation of bone metabolism, IL-1,IL-6 and TNF-regarded as key members of the cytokine network of the osteolysis in the microenvironment of the bone tissues. IL-1 and IL-6 not only directly stimulate bone resorption, but also strengthen the function of the other cytokine. And so they increase the function of bone resorption. TNF-stimulate pre-osteoclasts, and then the cellular proliferation and differentiation produce ripe osteclasts. At the same time, they affect the activity of bone alkaline phosphatase (BALP). BALP and BGP show the state of the high bone resorption and formation inversion in the postmenopausal osteoporosis. Yunke as a regulation material of ectogenetic calcium metabolism, when absorbed in bone tissues, it can control the formation of crystal calcium phosphonate, delay the congregate of apatite into large crystal, and at same time postpone the dissolution of crystal calcium phosphonate. When Yunke absorbed by the osteoclasts, it can directly repress the activity of osteoclasts and osteolysis (osteoclasia), depress the hypocalcemia, release osteocopic pain. Yunke has chelate ability to metal ions, and it can cut down the activity of metallaproteases and collagenase, and so it can refrain the bone disorganization of collagenase. Technetium is an artificial element ( technetium is one of the components of Yunke ). Technetium with lower valence is active, easy to gain or lose electrons. It can remove the free radicals in vivo, restrain the creation of the pathological compound and int