降钙的药物治疗课件.pptx

1、参考文献秦华东,石臣磊,石铁锋,等.急性高血钙危象6例临床分析J.医学临床研究,2008,25(10):1861-1863.Kenneth G.Saag,Jose R.Zanchetta,Jean-Pierre Devogelaer,etal.Effects of Teriparatide Versus Alendronate for Treating Glucocorticoid-Induced Osteoporosis:Thirty-SixMonth Results of a Randomized,Double-Blind,Contro-lled Trial J.ARTHRITIS&RHE

2、UMATISM,2009,60(11):33463355.Double-Blind,PlaceboControlled Study J.The Journal of Clinical Endocrino-logy&Metabolism,2007,92(4):13851390.J.Clin Endocrinol.Metab,2009,94(10):3798-3805.J.Scandinavian Journal of Surgery,2010,99:3237.降钙的药物治疗降钙的药物治疗 1.补钠利尿：补充0.9%氯化钠注射液既扩充了细胞外液又竞争性抑制了肾近曲小管对钙的重吸收,多数情况下第1个

3、24 h输注0.9%氯化钠注射液34 L,使每日尿量达到34 L。待血容量恢复正常后,静脉给予利尿剂,以袢利尿剂为主,因其可进一步阻断肾小管髓袢升支粗段对钠和钙的重吸收,促进尿钙排泄,常用呋塞米4080 mg静脉注射,必要时重复用药;而噻嗪类利尿剂应避免使用,因其可减少肾脏钙的排泄。秦华东,石臣磊,石铁锋,等.急性高血钙危象6例临床分析J.医学临床研究,2008,25(10):1861-1863.降钙的药物治疗降钙的药物治疗 2.应用骨溶解抑制剂：降钙素抑制破骨细胞对骨的吸收和肾小管对钙的重吸收,有利于钠和钙的排泄,作用迅速。降钙素100400 U,每6 h静脉或皮下注射1次,常用23次,但常

4、于几小时或几天内出现“脱逸”现象而失效。经降钙素治疗的患者,约80%血钙可降低,但难以恢复正常水平。二膦酸盐类药物的作用可能是对破骨细胞的直接毒性作用,尤其适用于高血钙伴低血磷的患者,低磷可使骨吸收和肾脏合成活性维生素D3增强,骨形成减少,高钙血症加重。秦华东,石臣磊,石铁锋,等.急性高血钙危象6例临床分析J.医学临床研究,2008,25(10):1861-1863.降钙的药物治疗降钙的药物治疗 二膦酸盐类药物依据时间先后和结构特点分为3代,包括:第1代的依替膦酸盐和氯甲双膦酸盐第2代的帕米膦酸盐、阿仑膦酸盐和利塞膦酸盐)以及第3代的伊苯膦酸盐、替鲁膦酸盐和唑来膦酸盐。第2代和第3代属于含氮原

5、子的二膦酸盐类药物,其抗骨重吸收能力是第1代的10010000倍。3.其他：如光辉霉素和甲状旁腺激素衍生物特立帕肽等。4.糖皮质激素：病情允许时可口服,紧急情况下可用氢化可的松或地塞米松静滴、静注。其虽有一定的降钙疗效,但起效慢,维持时间短。秦华东,石臣磊,石铁锋,等.急性高血钙危象6例临床分析J.医学临床研究,2008,25(10):1861-1863.Calcium-only group(n=9)Alendronate-treated group(n=7)975 0.Serum PTH,pg/ml 40.Baseline and 2 postbaseline serum calcium m

6、easurements were available for 196 subjects in each group.a)Friedmans test.predose serum calcium*文献四Subjects and Methods(4)Suppression of bone resorption(RR)by commercial isoflavone supplements and traditional pharmaceu-tical therapies,estra-diol or risedronate.The patients were randomized into two

7、study groups for a 5-year follow-up period.34)1.9 in the alendronate group vs.35)1.Gruen Zone Postoperative 6-m 5-y p valuea)Postoperative 6-m 5-y p value a)91 mmol/liter;P0.Calcium-only group(n=9)Alendronate-treated group(n=7)0 is the preintervention compar-ison.82 10.5 mg/dl 2.62 mmoles/liter was

8、determined from serum collected 16 hours after administration of study drugs.Kenneth G.Saag,Jose R.Zanchetta,Jean-Pierre Devogelaer,etal.Effects of Teriparatide Versus Alendronate for Treating Glucocorticoid-Induced Osteoporosis:Thirty-SixMonth Results of a Randomized,Double-Blind,Controlled TrialJ.

9、ARTHRITIS&RHEUMATISM,2009,60(11):33463355.文献二文献二Table 1.predose serum calcium*Subjects taking alendronate Subjects taking teriparatide P (n=214)(n=214)Predose total calcium1 serum calcium 14(7)44(21)0.0012 serum calcium 6(3)16(8)0.0461 serum calcium 3(1)9(4)0.1402 serum calcium 0 1(0.5)1.000*Predose

10、 was defined as_16 hours after administration of study drugs.To convert serum calcium concentrations to mmoles/liter multiply by 0.25.Baseline and 1 postbaseline serum calcium measurements were available for 209 subjects in the alendronate group and for 211 subjects in the teriparatide group.Baselin

11、e and 2 postbaseline serum calcium measurements were available for 196 subjects in each group.Kenneth G.Saag,Jose R.Zanchetta,Jean-Pierre Devogelaer,etal.Effects of Teriparatide Versus Alendronate for Treating Glucocorticoid-Induced Osteoporosis:Thirty-SixMonth Results of a Randomized,Double-Blind,C

12、ontrolled TrialJ.ARTHRITIS&RHEUMATISM,2009,60(11):33463355.文献三文献三:Subjects and Methods.Subjects and Methods.Patients were assigned to active oral alendronate or placebo within 10 d of acute SCI(Spinal Cord Association).Once weekly they took alendronate 70mg or matched placebo with water within a per

13、iod of 30 min while sitting upright and after overnight fasting.No supplement of dietary calcium was taken,but vitamin D was administered to those with low baseline serum vitaminD levels(25-hydroxyvitaminD50 nmol/liter).Treatment with alendronate and matched placebo was continued for 12 months,and p

14、atients were reviewed finally 6 months after cessation of therapy.文献三文献三Changes in biochemical markers from baseline over 18 months from alendronate or placebo.文献三文献三 Twenty-four-hour urinary calcium excretion was initially high in both groups(6.790.9 in the alendronate group vs.8.780.8 mmol/liter i

15、n the placebo group,not significant)but had decreased significantly in the alendronate group at 3 months(2.661.032 vs.9.130.91 mmol/liter;P0.001)and was still significantly less than the placebo group at 18 months(2.890.074 vs.3.90.65 mmol/liter;P0.001).文献四文献四Subjects and Methods(1)文献四文献四Subjects an

16、d Methods(2)The isoflavone profile of each supplement varied with the botanical source and the dose.Subjects were asked to take each intervention in divided doses throughout the day with meals but to consume all capsules/tablets by midnight.They were advised not to take extra pills on any day to com

17、pen-sate for previously missed pills.Either 1mg oral estradiol(Estrace)combined with 2.5 mg medroxyprogesterone daily or 5 mg/d of risedronate was used as the positive control for comparison.Participants were instructed to take risedronate on rising at least 30 min before consuming food or beve-rage

18、s and to take estrogen before breakfast.文献四文献四Subjects and Methods(3)Although subjects were not told which intervention they were on,the intervention regimen varied and tablets and capsules varied in number per day and appearance.Subjects were provided 500 mg/d calcium and 500 IU/d vitaminD3 through

19、out the study beginning at baseline to minimize fluctuations in calcium intakeand vitamin D status.The subjects completed a 3-d food record before and during each intervention period to assess their usual dietary pattern.文献四文献四Subjects and Methods(4)Calcium absorption Calcium absorption At the end o

20、f baseline and each intervention period,a calcium absorption test with 15.2 mg 44Ca as CaCO3 and the assigned supplement as part of a test meal containing 250 mg Ca was performed as previously described.44Ca enrichment was determined in the 5-h blood sample by Inductively Coupled Plasma and MassSpec

21、trometry as previously described.Fractional calcium absorption was determined as:(5-h SSA0.92373)0.3537(height meters0.52847)(weight kilograms0.37213)where SSA=serum-specific activity(fraction dose per gram Ca).文献四文献四FIG.2.FIG.2.Suppression of bone resorption(RR)by commercial isoflavone supplements

22、and traditional pharmaceu-tical therapies,estra-diol or risedronate.The line at RR=1.0 is the preintervention compar-ison.The error bars indicate 95%confidence interval about the mean.文献四文献四 Intervention,meanSD(minimum,maximum)Variable Baseline Estradiol/risedronate Soy cotyledon Urinary calcium,mmo

23、l/24h 7.43.1(2.9,14.3)8.17.1(2.1,25.4)9.17.9(2.0,26.3)Urinary phosphorous,mmol/24h 40.212.9(23.0,68.9)43.028.1(15.8,114.2)55.327.1(30.0,101.7)Serum PTH,pg/ml 40.023.7(15.8,95.8)45.617.5(28.5,78.5)41.526.7(10.7,104.2)Serum 25(OH)D,ng/ml 22.96.5(8.9,31.9)24.44.9(18.5,33.8)26.74.4(20,32.7)TABLE 1.Biom

24、arkers of bone turnover and calcium regulating hormones at baseline and at the end of each interventionn.s.:not significant.Intervention,meanSD(minimum,maximum)Variable Soy germ Red clover Kudzu P value Urinary calcium,mmol/24h 8.95.9(1.3,22.6)8.64.6(2.1,14.7)9.78.0(3.5,28.7)n.s.Urinary phosphorous,

25、mmol/24h 43.419.5(22.0,71.1)41.815.8(22.7,74.6)48.527.2(14.9,99.2)n.s.Serum PTH,pg/ml 40.520.6(14.9,82.4)43.928.3(11.5,114.6)35.326.2(11.2,102.4)n.s.Serum 25(OH)D,ng/ml 24.25.1(17.6,33.0)24.35.0(17.3,35.2)25.96.0(19.3,37.3)n.s.文献四文献四TABLE 2.Estimated RR due to interventionsaIntervention RR 95%Confid

26、enceinterval P valueEstrogen 0.756 0.700.82 0.0001Risedronate 0.783 0.730.84 0.0001Soy cotyledon 0.910 0.870.96 0.0002Soy germ 0.945 0.900.99 0.0312Red clover 0.958 0.911.10 0.0928Kudzu 0.975 0.931.02 0.3100an=11 except subjects either opted for estrogen(n=4)or risedronate(n=6)as a positive control.

27、文献五文献五MATERIALS AND METHODS(1)Sixteen patients participated in this prospective randomized controlled study.For inclusion to in this study,the patients neither suffered from any diseases affecting bone metabolism nor used any bone-inducing medication previously.Moreover,the patients understood not t

28、o use other bone growth-inducing medication during the study.The patients also had to be able to comply with a standard postoperative mobilization schedule.文献五文献五MATERIALS AND METHODS(2)The patients were randomized into two study groups for a 5-year follow-up period.Nine(five men and four women)rece

29、ived only 500 mg calcium carbonate daily.Seven(two men and five women)received 10 mg alendronate sodium(Fosamax)supplemented by 500 mg calcium carbonate daily.Alendronate tablets were administrated orally 30 minutes before the breakfast,beginning the first day after surgery.The duration of the treat

30、ment was 6 months.Serum calcium measurements.0 is the preintervention compar-ison.1 serum calcium 14(7)44(21)0.26)1.975 0.Baseline and 1 postbaseline serum calcium measurements were available for 209 subjects in the alendronate group and for 211 subjects in the teriparatide group.如光辉霉素和甲状旁腺激素衍生物特立帕肽

31、等。Scandinavian Journal of Surgery,2010,99:3237.Subjects were asked to take each intervention in divided doses throughout the day with meals but to consume all capsules/tablets by midnight.文献四Subjects and Methods(2)945 0.41)NS 1.9 in the alendronate group vs.an=11 except subjects either opted for est

32、rogen(n=4)or risedronate(n=6)as a positive control.No supplement of dietary calcium was taken,but vitamin D was administered to those with low baseline serum vitaminD levels(25-hydroxyvitaminD50 nmol/liter).38)NS 1.Study design and participants.医学临床研究,2008,25(10):1861-1863.文献四Subjects and Methods(2)

33、At the end of baseline and each intervention period,a calcium absorption test with 15.待血容量恢复正常后,静脉给予利尿剂,以袢利尿剂为主,因其可进一步阻断肾小管髓袢升支粗段对钠和钙的重吸收,促进尿钙排泄,常用呋塞米4080 mg静脉注射,必要时重复用药;而噻嗪类利尿剂应避免使用,因其可减少肾脏钙的排泄。文献文献五五The mean periprosthetic BMD(SD)in the Calcium-only and Alendronate-treated groups during the 5-year

34、 follow-up time.Calcium-only group(n=9)Alendronate-treated group(n=7)Gruen Zone Postoperative 6-m 5-y p valuea)Postoperative 6-m 5-y p value a)1 0.95(0.17)0.85(0.18)0.80(0.26)NS 0.93(0.24)0.96(0.19)0.91(0.22)NS2 1.89(0.20)1.64(0.41)1.64(0.48)0.045 1.81(0.25)1.72(0.32)1.72(0.29)NS3 2.02(0.27)1.94(0.3

35、5)1.91(0.49)NS 1.86(0.35)1.81(0.36)1.84(0.37)NS4 1.81(0.26)1.74(0.28)1.71(0.41)NS 1.72(0.34)1.67(0.35)1.67(0.40)NS5 2.00(0.25)1.92(0.27)1.98(0.38)NS 1.88(0.26)1.85(0.22)1.88(0.28)NS6 1.55(0.30)1.43(0.30)1.45(0.38)NS 1.56(0.08)1.54(0.21)1.58(0.18)NS7 1.10(0.15)0.91(0.16)0.79(0.22)0.000 1.17(0.26)1.12

36、(0.34)0.98(0.35)0.02 totROI 1.62(0.17)1.49(0.21)1.47(0.32)0.004 1.56(0.23)1.52(0.25)1.50(0.27)NSprROI 1.02(0.13)0.88(0.15)0.79(0.23)0.001 1.05(0.24)1.04(0.24)0.90(0.25)0.05 a)Friedmans test.NS=Not Significant,prROI=the proximal part of the femur,totROI=total femoral regions of interest.参考文献秦华东,石臣磊,石

37、铁锋,等.急性高血钙危象6例临床分析J.医学临床研究,2008,25(10):1861-1863.Kenneth G.Saag,Jose R.Zanchetta,Jean-Pierre Devogelaer,etal.Effects of Teriparatide Versus Alendronate for Treating Glucocorticoid-Induced Osteoporosis:Thirty-SixMonth Results of a Randomized,Double-Blind,Contro-lled Trial J.ARTHRITIS&RHEUMATISM,2009,

38、60(11):33463355.Double-Blind,PlaceboControlled Study J.The Journal of Clinical Endocrino-logy&Metabolism,2007,92(4):13851390.J.Clin Endocrinol.Metab,2009,94(10):3798-3805.J.Scandinavian Journal of Surgery,2010,99:3237.文献三文献三 Twenty-four-hour urinary calcium excretion was initially high in both group

39、s(6.790.9 in the alendronate group vs.8.780.8 mmol/liter in the placebo group,not significant)but had decreased significantly in the alendronate group at 3 months(2.661.032 vs.9.130.91 mmol/liter;P0.001)and was still significantly less than the placebo group at 18 months(2.890.074 vs.3.90.65 mmol/li

40、ter;P16 hours after administration of study drugs.Zanchetta,Jean-Pierre Devogelaer,etal.Study design and participants.Red clover 0.Suppression of bone resorption(RR)by commercial isoflavone supplements and traditional pharmaceu-tical therapies,estra-diol or risedronate.10 0.降钙素抑制破骨细胞对骨的吸收和肾小管对钙的重吸收,

41、有利于钠和钙的排泄,作用迅速。Fractional calcium absorption was determined as:(5-h SSA0.Clin Endocrinol.Urinary calcium,mmol/24h 8.Zanchetta,Jean-Pierre Devogelaer,etal.49)NS 1.Soy cotyledon 0.急性高血钙危象6例临床分析J.99 0.91 mmol/liter;P0.Effects of Teriparatide Versus Alendronate for Treating Glucocorticoid-Induced Osteop

42、orosis:Thirty-SixMonth Results of a Randomized,Double-Blind,Controlled TrialJ.25)1.待血容量恢复正常后,静脉给予利尿剂,以袢利尿剂为主,因其可进一步阻断肾小管髓袢升支粗段对钠和钙的重吸收,促进尿钙排泄,常用呋塞米4080 mg静脉注射,必要时重复用药;而噻嗪类利尿剂应避免使用,因其可减少肾脏钙的排泄。91 mmol/liter;P0.1 serum calcium 3(1)9(4)0.an=11 except subjects either opted for estrogen(n=4)or risedronat

43、e(n=6)as a positive control.The error bars indicate 95%confidence interval about the mean.10 0.001)and was still significantly less than the placebo group at 18 months(2.NS=Not Significant,prROI=the proximal part of the femur,totROI=total femoral regions of interest.34)1.降钙素抑制破骨细胞对骨的吸收和肾小管对钙的重吸收,有利于

44、钠和钙的排泄,作用迅速。Intervention,meanSD(minimum,maximum)Serum PTH,pg/ml 40.23)1.35)1.1 serum calcium 14(7)44(21)0.26)1.38)NS 1.文献四Subjects and Methods(1)The error bars indicate 95%confidence interval about the mean.Calcium absorption24)0.急性高血钙危象6例临床分析J.91 mmol/liter;P0.Serum 25(OH)D,ng/ml 22.1 serum calcium

45、 3(1)9(4)0.Saag,Jose R.急性高血钙危象6例临床分析J.待血容量恢复正常后,静脉给予利尿剂,以袢利尿剂为主,因其可进一步阻断肾小管髓袢升支粗段对钠和钙的重吸收,促进尿钙排泄,常用呋塞米4080 mg静脉注射,必要时重复用药;而噻嗪类利尿剂应避免使用,因其可减少肾脏钙的排泄。26)1.a)Friedmans test.groups during the 5-year follow-up time.26)1.医学临床研究,2008,25(10):1861-1863.Biom arkers of bone turnover and calcium regulating hormo

46、nes at baseline and at the end of each intervention24)0.49)NS 1.文献五MATERIALS AND METHODS(1)10 0.Seven(two men and five women)received 10 mg alendronate sodium(Fosamax)supplemented by 500 mg calcium carbonate daily.49)NS 1.降钙素抑制破骨细胞对骨的吸收和肾小管对钙的重吸收,有利于钠和钙的排泄,作用迅速。91 mmol/liter;P0.34)1.The error bars i

47、ndicate 95%confidence interval about the mean.0 is the preintervention compar-ison.文献文献五五The mean periprosthetic BMD(SD)in the Calcium-only and Alendronate-treated groups during the 5-year follow-up time.Calcium-only group(n=9)Alendronate-treated group(n=7)Gruen Zone Postoperative 6-m 5-y p valuea)P

48、ostoperative 6-m 5-y p value a)1 0.95(0.17)0.85(0.18)0.80(0.26)NS 0.93(0.24)0.96(0.19)0.91(0.22)NS2 1.89(0.20)1.64(0.41)1.64(0.48)0.045 1.81(0.25)1.72(0.32)1.72(0.29)NS3 2.02(0.27)1.94(0.35)1.91(0.49)NS 1.86(0.35)1.81(0.36)1.84(0.37)NS4 1.81(0.26)1.74(0.28)1.71(0.41)NS 1.72(0.34)1.67(0.35)1.67(0.40)

49、NS5 2.00(0.25)1.92(0.27)1.98(0.38)NS 1.88(0.26)1.85(0.22)1.88(0.28)NS6 1.55(0.30)1.43(0.30)1.45(0.38)NS 1.56(0.08)1.54(0.21)1.58(0.18)NS7 1.10(0.15)0.91(0.16)0.79(0.22)0.000 1.17(0.26)1.12(0.34)0.98(0.35)0.02 totROI 1.62(0.17)1.49(0.21)1.47(0.32)0.004 1.56(0.23)1.52(0.25)1.50(0.27)NSprROI 1.02(0.13)0.88(0.15)0.79(0.23)0.001 1.05(0.24)1.04(0.24)0.90(0.25)0.05 a)Friedmans test.NS=Not Significant,prROI=the proximal part of the femur,totROI=total femoral regions of interest.