Clinical Research On Efficacy And Security Of Moderate Skeletal Fluorosis Treated By Guo's Therapy

Clinical observation of efficacy and security of moderate skeletal fluorosis treated by Guo's therapyBackground:Skeletal fluorosis is caused by people living in high fluoride environment and intaking of excessive fluoride, which result in the disorders of bone and joints.Its main symptoms are joint pain and deformities, joint stiffness and activities restricted, and even paralyze. The disease is the most serious endemie disease with the widest distribution in our country, According to data released by the Ministry of Health, at of the end of 2006, In China, There are endemic areas of 1316 counties with about 3813 million dental fluorosis patients,329 million Skeletal fluorosis patients.Currently, modern medicine for patients with moderate skeletal fluorosis is lack of effective therapy,patients always intake of calcium, magnesium, boron and other trace elements to reduce the body's absorption of fluoride and promote excretion of fluoride. because pathogenesis of skeletal fluorosis is not entirely clear, modern medicine is still lack of specific drugs and radical measures.In recent years, Chinese medicine has made great progress in prevention and treatment skeletal fluorosis through its theory of overall concept,syndrome differentiation and a variety of treatment methods.Doctor Guo Peihua has achieved a certain effect on treating skeletal fluorosis mainly based on TCM treatment of Strychnine in the past years, provides a useful exploration of drug dosage form,administration route and other aspects of western medicine with Chinese medicine.The first part clinical effect research1 Objective:this subject adopt randomized controlled methods based on clear diagnosis, unified observation content, establish symptoms and signs quantitative indicators, combined with PRO scales to evaluate the efficacy of skeletal fluorosis patients, strictly observe the changes of symptoms and signs before and after treatment, aiming at observation and evaluation the efficacy of the Kuo's therapy in treatment moderate skeletal fluorosis. 2Materials and Methods:From December 2007 to July 2009,120 moderate skeletal fluorosis patients met the inclusion criteria are devided into the treatment group 60 cases and control group 60 cases by randomized controlled method, the treatment group intake of calcium D 600 and Kuo's therapy (the main component is Strychnine, according to patient responses to gradually increase Strychnine dose), the control group intake of calcium D 600 and placebo.The course of treatment is 12 weeks, followed up 24 weeks, At the time of before treatment, 1 week,2 weeks,3 weeks,4 weeks,8 weeks,12 weeks,24 weeks,36 weeks after treatment, The third party evaluate the symptoms of pain, morning stiffness, numbness, tight feeling, convulsions and the signs of upper extremity functions, lower extremity functions, single-joint movement disorders and spinal function. Also evaluate Clinical effiect by the disappearance rate of symptoms or dysfunction, the improvement rate of symptom scores or dysfunction scores, comprehensive improvement rate of symptoms and signs, X-ray analysis combined with PRO scales.The data is analyzed by SAS9.03 software.3Results:3.1 symptoms improvement results3.1.1 The group comparison:the improvement rate of pain and the disappearance rate of morning stiffness, numbness, tense feeling and convulsions gradually increase with treatment time prolonged in the treatment group and the control group, and compared with those before treatment, the difference is statistically significant (P<0.05, P<0.01).3.1.2 The comparison between the two groups:the improvement rate of pain and the disappearance rate of morning stiffness, numbness, tense feeling and convulsions in the treatment group are superior to that in the control group significantly, compared with that in the control group, the difference is statistically significant (P<0.01). After treatment, the disappearance rate of numbness in the treatment group compared with that in the control group has not statistically difference (P> 0.05).3.1.3 At the end of treatment:at the end of treatment in 12 weeks, the improvement rate of pain and comprehensive symptoms is better than those before treatment in the two groups. The improvement rate of pain is 96.67% in the treatment group and 33.33% in the control group, The former is better than the latter with statistically difference(P<0.01).The improvement rate of comprehensive symptoms is 96.67% in treatment group and 47.37% in the control group, The former is better than the latter with statistically difference(P<0.01). 3.1.4 At the end of follow-up:at the end of follow-up in 36 weeks, the improvement rate of pain and comprehensive symptoms is better than those before treatment in the two groups. The improvement rate of pain is 98.33% in the treatment group and 35.09% in the control group, the former is better than the latter with statistically difference(P<0.01).The improvement rate of comprehensive symptoms is 96.67% in treatment group and 54.39% in the control group, The former is better than the latter with statistically difference(P<0.01).3.2 Signs improvement results3.2.1 The group comparison:The disappearance rate of upper extremity dysfunctions, lower extremity dysfunctions and single joint dysfunctions gradually increase with treatment time prolonged in the treatment group, and better than those before treatment with statistically difference (P<0.05, P<0.01).The disappearance rate of upper extremity dysfunction and lower extremity dysfunction gradually increase with treatment time prolonged in the control group, and better than those before treatment with statistically difference (P <0.05, P<0.01). The disappearance rate of the other upper dysfunction and single joint dysfunctions has no significant change after treatment with no statistically difference (P> 0.05).3.2.2 The comparison between the two groups:The disappearance rate of upper extremity dysfunctions, lower extremity dysfunctions and single joint dysfunctions in the treatment group is superior to that in the control group significantly with statistically difference (P<0.01). After treatment, Spinal function in two groups showed no significant difference, the difference was not statistically significant (P> 0.05).3.2.3 At the end of treatment:at the end of treatment in 12 weeks, the improvement rate of comprehensive signs is better than that before treatment in the two groups. The improvement rate of comprehensive signs is 88.33% in the treatment group and 28.07% in the control group, the former is better than the latter with statistically difference(P<0.01).3.2.4 At the end of follow-up:at the end of follow-up in 36 weeks, the improvement rate of comprehensive signs is better than before treatment in the two groups. The improvement rate of comprehensive signs is 93.33% in the treatment group and 40.35% in the control group, the former is better than the latter with statistically difference(P<0.01).3.3 Comprehensive symptoms and signs improvement results3.3.1 At the end of treatment:In the treatment group, there are recovered 2 cases on comprehensive clinical effect, accounting for 3.33%; markedly effective 20 cases, accounting for 33.33%; effective 24 cases, accounting for 40.00%; improvement 10 cases, accounting for 16.67%; ineffective 4 cases, accounting for 6.67%. Total improvement rate is 93.33%.In the control group, there are recovered 0 cases on comprehensive clinical effect, markedly effective Ocases; effective 2cases, accounting for 3.51%; improvement 22 cases, accounting for 38.60%; ineffective 33 cases, accounting for 57.89%. Total improvement rate is 42.11%. The difference of Comprehensive clinical effect between the two groups is statistically significant (P<0.01).3.3.2 At the end of follow-up:In the treatment group, there are recovered4cases on comprehensive clinical effect, accounting for6.67%; markedly effective32cases, accounting for 53.33%; effective 16cases, accounting for 26.67%; Improvements cases, accounting for 8.33%; ineffective 3cases, accounting for 5.00%. Total improvement rate is 95.00%.In the control group, there are recovered 0 cases on comprehensive clinical effect, Markedly effective Ocases; Effective 4cases, accounting for 7.02%; Improvement 26 cases, accounting for 45.61%; ineffective 27 cases, accounting for 47.37%. Total improvement rate is 52.63%. The difference of comprehensive clinical effect between the two groups is statistically significant (P<0.01).3.4 PRO scales evaluation results3.4.1 Self-feeling symptoms improvement results:self-assessment by skeletal fluorosis PRO scales shows that the symptoms of pain, numbness, stiff joints, the limbs twitch, and body tight in the two groups are better than those before treatment, compared with those before treatment, the difference is statistically significant (P<0.05).After treatment, the improvement results of the above-mentioned symptoms in the treatment group are better than those in the control group with statistically significant (P<0.01).3.4.2 Self-feeling abilities improvement results:The abilities of walking, flexibility, self-care and work in two groups are better than thosebefore treatment, compared with those before treatment, the difference is statistically significant (P <0.05). After treatment, the improvement results of the above-mentioned abilities in the treatment group are better than those in the control group with statistically significant (P<0.01).3.4.3 Comprehensive scores improvement results:self-feeling comprehensive scores in two groups are better than those before treatment, compared with those before treatment, the difference is statistically significant (P<0.01). improvement effect in the treatment group is better than that in the control group with statistically significant (P<0.01).3.5 X-ray analysis results:3.5.1 X-ray Typical performance:sclerosis,osteoporosis,osteomalacia,Bone border changes and bone turnover are the main X-ray performance.Among them, sclerosis and bone turnover are lower incidience, osteoporosis and Bone border changes are higher incidience in the radiological manifestations.3.5.2 improvement after treatment:After treatment, there is no significant change in X-ray in the two groups, no significant difference between the two groups, the difference was not statistically significant (P> 0.05).4Conclusion:4.1 The treatment group and the control group can ease the symptoms of pain, morning stiffness, numbness, tense feeling, convulsions, the improvement rate of pain and the disappearance rate of morning stiffness, numbness, tense feeling and convulsions in the treatment group are better than that in the control group significantly from 4 weeks after treatment until the end of treatment.4.2 The treatment group and the control group can improve upper extremity functions, lower extremity functions and single-joint dysfunctions, the disappearance rate of upper extremity dysfunctions, lower extremity dysfunctions and single joint dysfunctions in the treatment group are better than that in the control group significantly from 4 weeks after treatment until the end of treatment. There is no significant difference between the two groups on spinal function.4.3 The treatment group and the control group can improve comprehensive symptoms and signs effect, the comprehensive symptoms and signs effect in the treatment group are better than those in the control group at the end of treatment and follow-up.4.4self-assessment by skeletal fluorosis PRO scales shows that the symptoms of pain, numbness, stiff joints, the limbs twitch, and body tight in the two groups are better than those before treatment, improvement effect of symptoms in the treatment group is higher than that in the control group. The abilities of walking, flexibility, self-care and work in two groups are better than those before treatment, improvement effect of abilities in the treatment group is higher than that in the control group.4.5 Image evaluation is not improved after treatment in the treatment group and control group.The second part security research1 Objective:1.1 through Strychnine alkaloid content determination, judge the safety of clinical medicine.1.2 through clinical observation and physical examination, evaluate the security of Guo's therapy on treating patients with moderate skeletal fluorosis.2 Methods:2.1 Test Strychnine alkaloid content and brucine content in health products and processed products of Strychnine repeattedly twice referring to pharmacopoeia method, determine the content standard of these two components.2.2 Analyze Strychnine alkaloid content in Guo's Ma Qian Tang and Strychni according to Strychnine daily dosage and test results, compare with the maximum limit in pharmacopoeia and the actual content.2.3 During the course of intaking of Guo's Ma Qian Tang, test Strychnine alkaloid blood concentration.2.4 During the course of treatment, close observe clinical adverse reactions and blood routine, urine routine, stool routine, liver function, kidney function and ECG, analyze the relationship between taking strychni dose and adverse reactions, give symptomatic treatment necessarily.3 Results3.1 Strychnine alkaloid content determination resultsThe brucine content and strychnine alkaloid content in health products and processed products of Strychnine meet pharmacopoeia standards.3.2 Strychnine alkaloid content determination results in Guo's Ma Qian Tangwhen the maximum dose of Strychnine is 1.2g in Guo's Ma Qian Tang, Strychnine content is 11.17mg and brucine content is 7.44mg, this results meet the pharmacopoeia standards of Strychnine content and brucine content.3.3 Strychnine alkaloid content determination results in blood samplesresults show that brucine and strychnine alkaloid content are not detected in blood samples or below 100ng/ml in the plasma concentration, also not accumulation in the blood during medication and 8 weeks after medication.3.4 The relationship between Strychnine dose and treatment responseresults show that 51 patients have not any adverse reactions in the treatment group when Strychnine dose is gradually increased 1.2g,9 patients have the symptoms of tongue numbness, stiff tongue, headache, dizziness and slight sweating,1 patient has dizziness, the right hemifacial numbness, mouth chewing symptoms when the dose of 1.1g, symptoms relieve when giving patients Strychnine dose reduced to 1.05g. The remaining 8 patients treatment response disappear by the close observation, continuing to give increasing doses until Strychnine dose to 1.2g, patients have no treatment reaction recurrently.3.5 ECG and laboratory tests resultsbefore and after treatment, ECG, blood routine, urine routine, stool routine, liver function, kidney function tests have no significant changes in treatment group and control group.4 Conclusion: Guo's therapy by gradually increasing Strychnine dose on treating moderate skeletal fluorosis is safe and effective because brucine and strychnine alkaloid don't accumulate in plasma and clinical observation of toxicity does not occur.5Innovation:5.1This subject is the first research on efficacy and safety of Chinese medicine treatment in endemic skeletal fluorosis by randomized, controlled, third-party blinded evaluation.5.2 this subject formulate a more comprehensive quantitative indicators of symptoms and signs, and combined with other qualitative indicators, provide a more comprehensive method for observation and evaluation on skeletal fluorosis effect.5.3 This subject first adopt PRO scales to evaluate the efficacy and safety of the skeletal fluorosis patients. Combined with self-evaluation on treatment results, so the results are more objective and comprehensive.5.4 This subject adopt the methods of gradually increasing Strychnine dose with individual differences, ensure the clinical safety, avoid or reduce strychnos toxicity.