健肾方联合碳酸钙D3咀嚼片(Ⅱ)治疗绝经后骨质疏松症肾阳虚证

Oral application of Jianshen Fang(健肾方) and calcium carbonate and Vitamin D3 chewable tablets(Ⅱ) for treatment of postmenopausal osteoporosis with kidney-yang deficiency syndrome

目的:观察健肾方联合碳酸钙D3咀嚼片(Ⅱ)治疗绝经后骨质疏松症(postmenopausal osteoporosis,PMOP)肾阳虚证的临床疗效和安全性。方法:选取80例符合要求的PMOP肾阳虚证患者,随机分为2组,每组40例。健肾方组采用口服健肾方联合碳酸钙D3咀嚼片(Ⅱ)治疗,阿仑膦酸钠组采用口服阿仑膦酸钠片联合碳酸钙D3咀嚼片(Ⅱ)治疗,共治疗6个月。分别于治疗前和治疗结束后测定患者的骨密度、疼痛程度、血清雌二醇(Estradiol,E2)、骨保护素和胰岛素样生长因子Ⅰ(insulin-like growth factorⅠ,IGF-Ⅰ)含量,观察不良反应的发生情况。结果:健肾方组2例出现肝功能指标异常,2例出现肾功能指标异常;阿仑膦酸钠组1例出现肝功能指标异常,1例出现肾功能指标异常。对于出现不良反应的患者均立即停止使用当前药物,给予护肝及保护肾功能等对症处理后,患者的肝肾功能指标均在2周内恢复至正常范围。2组患者的不良反应发生率比较,差异无统计学意义(χ2=0.180,P=0.671)。治疗前2组患者的骨密度比较,差异无统计学意义(t=1.014,P=0.314);治疗结束后2组患者的骨密度均较治疗前增加(-2.69±0.12,-2.09±0.22,t=14.343,P=0.000;-2.72±0.13,-2.37±0.09,t=14.038,P=0.000),健肾方组的骨密度高于阿仑膦酸钠组(t=6.931,P=0.000)。治疗前2组患者的疼痛视觉模拟量表(visual analogue scale,VAS)评分比较,差异无统计学意义(t=0.465,P=0.644);治疗结束后2组患者的疼痛VAS评分均较治疗前降低[(4.53±0.94)分,(2.33±0.68)分,t=11.366,P=0.000;(4.42±1.03)分,(3.21±0.87)分,t=5.522,P=0.000],健肾方组的VAS评分低于阿仑膦酸钠组(t=4.841,P=0.000)。治疗前2组患者的血清E2含量比较,差异无统计学意义(t=0.511,P=0.611);治疗结束后健肾方组的血清E2含量较治疗前升高[(50.91±6.24)pmol·L^(-1),(62.88±9.02)pmol·L^(-1),t=6.546,P=0.000];阿仑膦酸钠组血清E2含量与治疗前相比,差异无统计学意义[(50.17±6.31)pmol·L^(-1),(50.88±8.16)pmol·L^(-1),t=0.425,P=0.672];治疗结束后,健肾方组的血清E2含量高于阿仑膦酸钠组(t=6.006,P=0.000)。治疗前2组患者的血清骨保护素含量比较,差异无统计学意义(t=0.348,P=0.729);治疗结束后2组患者的血清骨保护素含量均较治疗前升高[(140.76±14.97)pg·m L^(-1),(160.18±15.70)pg·m L^(-1),t=5.371,P=0.000;(139.55±14.99)pg·m L^(-1),(146.68±15.68)pg·m L^(-1),t=2.027,P=0.046],健肾方组的血清骨保护素含量高于阿仑膦酸钠组(t=3.701,P=0.000)。治疗前2组患者的血清IGF-Ⅰ含量比较,差异无统计学意义(t=0.839,P=0.404);治疗结束后2组患者的血清IGF-Ⅰ含量均较治疗前升高[(25.19±8.34)μg·L^(-1),(35.81±9.48)μg·L^(-1),t=5.042,P=0.000;(23.53±8.74)μg·L^(-1),(28.87±10.29)μg·L^(-1),t=2.440,P=0.017],健肾方组的血清IGF-Ⅰ含量高于阿仑膦酸钠组(t=3.012,P=0.004)。结论:健肾方联合碳酸钙D3咀嚼片(Ⅱ)能提高PMOP肾阳虚证患者血清E2、骨保护素及IGF-Ⅰ含量,增加患者的骨密度、减轻疼痛程度,其效果优于阿仑膦酸钠片联合碳酸钙D3咀嚼片(Ⅱ)治疗,而且具有较高的安全性。

Objective： To observe the clinical curative effects and safety of oral application of Jianshen Fang（ 健肾方,JSF） and calcium carbonate and Vitamin D3 chewable tablets（ Ⅱ） for treatment of postmenopausal osteoporosis（ PMOP） with kidney-yang deficiency syndrome. Methods： Eighty patients with kidney-yang deficiency type PMOP were enrolled in the study and randomly divided into 2 groups,40 cases in each group,and were treated with oral application of JSF and calcium carbonate and Vitamin D3 chewable tablets（ Ⅱ）（ JSF group） and oral application of alendronate sodium tablets and calcium carbonate and Vitamin D3 chewable tablets（ Ⅱ）（ alendronate sodium group） respectively for consecutive 6 months. Bone density,pain degree and serum contents of Estradiol（ E2）,osteoprotegerin（ OPG） and insulin-like growth factor Ⅰ（ IGF-Ⅰ） were measured and compared between the 2 groups before treatment and after the end of the treatment respectively,and the incidence rate of adverse reactions was observed. Results： Abnormal liver function indexes were found in 2 patients in JSF group and 1 patient in alendronate sodium group,and abnormal kidney function indexes were found in 2 patients in JSF group and 1 patient in alendronate sodium group. The drugs which caused adverse effects were withdrew immediately and liver and kidney protective agents were used,and the liver and kidney function recovered from injury 2 weeks later. There was no statistical difference in the incidence rate of adverse reactions between the 2 groups（ χ^2= 0. 180,P = 0. 671）. There was no statistical difference in the bone density between the 2 groups before the treatment（ t = 1. 014,P = 0. 314）. The bone density increased after the end of the treatment compared to pretreatment in the 2 groups（-2. 69 ＋/-0. 12 vs-2. 09 ＋/-0. 22,t = 14. 343,P = 0. 000;-2. 72 ＋/-0. 13 vs-2. 37 ＋/-0. 09,t =14. 038,P = 0. 000）,and was higher in JSF group compared to alendronate sodium group（ t = 6. 931,P = 0. 000）. There was no statistical difference in pain visual analogue scale（ VAS） scores between the 2 groups before the treatment（ t = 0. 465,P = 0. 644）. The pain VAS scores decreased after the end of the treatment compared to pretreatment in the 2 groups（ 4. 53 ＋/-0. 94 vs 2. 33 ＋/-0. 68 points,t =11. 366,P = 0. 000; 4. 42 ＋/-1. 03 vs 3. 21 ＋/-0. 87 points,t = 5. 522,P = 0. 000）,and was lower in JSF group compared to alendronate sodium group（ t = 4. 841,P = 0. 000）. There was no statistical difference in serum contents of E2 between the 2 groups before the treatment（ t = 0. 511,P = 0. 611）. The serum contents of E2 increased after the end of the treatment compared to pretreatment in JSF group（ 50. 91 ＋/-6. 24 vs 62. 88 ＋/-9. 02 pmol/L,t = 6. 546,P = 0. 000）. There was no statistical difference in serum contents of E2 between pre-treatment and post-treatment in alendronate sodium group（ 50. 17 ＋/-6. 31 vs 50. 88 ＋/-8. 16 pmol/L,t = 0. 425,P = 0. 672）. The serum contents of E2 were higher in JSF group compared to alendronate sodium group after the end of the treatment（ t = 6. 006,P =0. 000）. There was no statistical difference in serum contents of OPG between the 2 groups before the treatment（ t = 0. 348,P = 0. 729）. The serum contents of OPG increased after the end of the treatment compared to pretreatment in the 2 groups（ 140. 76 ＋/-14. 97 vs160. 18 ＋/-15. 70 pg/m L,t = 5. 371,P = 0. 000; 139. 55 ＋/-14. 99 vs 146. 68 ＋/-15. 68 pg/m L,t = 2. 027,P = 0. 046）,and were higher in JSF group compared to alendronate sodium group（ t = 3. 701,P = 0. 000）. There was no statistical difference in serum contents of IGF-Ⅰbetween the 2 groups before the treatment（ t = 0. 839,P = 0. 404）. The serum contents of IGF-Ⅰincreased after the end of the treatment compared to pretreatment in the 2 groups（ 25. 19 ＋/-8. 34 vs 35. 81 ＋/-9. 48 μg/L,t = 5. 042,P = 0. 000; 23. 53 ＋/-8. 74 vs 28. 87 ＋/-10. 29 μg/L,t = 2. 440,P = 0. 017）,and were higher in JSF group compared to alendronate sodium group（ t = 3. 012,P = 0. 004）. Conclusion： Oral application of JSF and calcium carbonate and Vitamin D3 chewable tablets（ Ⅱ） can increase the serum contents of E2,OPG and IGF-Ⅰand improve bone density and alleviate pain in patients with kidney-yang deficiency type PMOP,and its curative effect is better than that of oral application of alendronate sodium tablets and calcium carbonate and Vitamin D3 chewable tablets（ Ⅱ）,moreover,it has high safety.