阿法骨化醇对甲状腺自身免疫状态的影响

目的：探讨补充阿法骨化醇对甲状腺自身免疫状态的影响。方法选取2013年6月-2015年3月就诊的未经治疗的甲状腺自身免疫患者[血清抗甲状腺过氧化物酶抗体（ TPOAb）﹥34μIU/ ml,即单纯 TPOAb 阳性],根据 TPOAb 水平分为 TPOAb ﹤500μIU/ ml 组、TPOAb 500~1000μIU/ ml 组及 TPOAb ﹥1000μIU/ ml 组,每组再依据阿法骨化醇给药剂量分为0.5μg 组和1.0μg 组,每3个月测定1次患者的甲状腺功能水平（TSH、FT3、FT4）和 TPOAb水平,共12个月。结果阿法骨化醇可以降低 TPOAb 水平,且0.5μg 组和1.0μg 组相比,TPOAb 水平下降例数无统计学差异（P ﹥0.05）;3个不同 TPOAb 水平组相比,TPOAb 水平下降例数差异无统计学意义（P ﹥0.05）。结论自身免疫性甲状腺疾病（AITD）补充阿法骨化醇可能有助于降低血清甲状腺自身抗体 TPOAb 水平,抑制甲状腺自身免疫反应的作用。     

不同剂量阿法骨化醇治疗IgA肾病的临床观察

目的:观察不同剂量阿法骨化醇治疗IgA肾病(IgAN)的临床疗效和安全性。方法:将62例IgAN患者按随机数字表法均分为对照组和观察组。两组患者均给予低盐、低脂、低蛋白饮食,维持原有肾素血管紧张素系统(RAS)阻滞药双倍剂量不变等常规治疗。在此基础上,对照组患者给予阿法骨化醇胶丸0.25μg,口服,qd;观察组患者给予阿法骨化醇胶丸0.5μg,口服,qd。合并高血压患者在血压不达标的情况下加服长效钙离子拮抗药控制血压。两组患者疗程均为12周。观察两组患者临床疗效,治疗前后血清胱抑素C(Cys-C)、血尿素氮(BUN)、血肌酐(Scr)、血钙(Ca)、血磷(P)、血全段甲状旁腺激素(iPTH)、24小时尿蛋白定量(24 hUTP)、平均动脉压(MAP)及不良反应发生情况。结果:治疗后观察组患者总有效率显著高于对照组,Cys-C、24 hUTP均显著低于对照组,差异有统计学意义(P<0.05)。两组患者治疗前后BUN、Scr、Ca、P、iPTH、MAP比较,差异均无统计学意义(P>0.05)。两组患者治疗期间均未见明显不良反应发生。结论:大剂量阿法骨化醇可更有效地降低IgAN患者尿蛋白水平、保护肾功能,且安全性较好。     

益肾健骨法对原发性骨质疏松症的临床研究

目的 了解近3年来就诊于江苏省中医院内分泌科患者骨质疏松、骨量减少发生情况,制定预防措施。验证中医益肾健骨法在治疗骨质疏松中的疗效。方法 通过对南京地区骨质疏松症及骨量减少的筛选,设定对照组（阿法骨化醇0.5μg,qd）、治疗组（阿法骨化醇0.5μg,qd+健骨丸5g,bid）,观察患者临床表现,监测血钙、磷及骨密度两年。结果 治疗1年时,中药治疗组临床症状缓解明显;第二年时中药治疗组的跟骨骨密度增加明显优于对照组,血钙、血磷由于自身代谢及合理饮食改变不明显。结论 中药制剂健骨丸对骨质疏松有明显的疗效。     

Intravenous alfacalcidol once weekly suppresses parathyroid hormone in hemodialysis patients

Management of secondary hyperparathyroidism is difficult because of the interrelationship of parathyroid hormone, calcium and phosphorus. This study was carried out to assess the efficacy of intravenous administration of alfacalcidol once weekly versus twice weekly in patients with severe hyperparathyroidism. Twenty-one hemodialysis patients with intact parathyroid hormone >88 pmol/L were divided into two groups. Eleven patients (Group 1) were given a once-weekly alfacalcidol intravenously for 12 weeks. The starting dose was 4 microg which was increased or decreased by 1 microg per week. Ten patients (Group 2) were given twice-weekly alfacalcidol intravenously for 12 weeks. The starting dose was 2 microg twice weekly which was increased or decreased by 0.5 microg/dose. The dose was increased or decreased according to serum calcium and phosphorus levels. Serum calcium, phosphorus and alkaline phosphatase levels were measured weekly and intact parathyroid hormone every 4 weeks. Intact parathyroid hormone reduced significantly (P = 0.0001) from 128.12 +/- 35.42 pmol/L to 82.93 +/- 65.20 pmol/L and from 113.74 +/- 40.83 pmol/L to 64.24 +/- 35.17 pmol/L after 4 weeks in Groups 1 and 2, respectively. After 4 weeks alkaline phosphatase declined significantly (P = 0.0001) from 146.0 +/- 57.3 IU/L to 116.0 +/- 45.6 IU/L in Group 1 and from 139.0 +/- 45.1 IU/L to 116.6 +/- 38 IU/L in Group 2. There were no significant differences in serum levels of calcium, phosphorous or their product. Interestingly, an adenoma disappeared in one patient from Group 1, and out of two adenomas, one disappeared from another patient in the same group. These results indicate that intravenous alfacalcidol once weekly is safe and effective in suppressing high parathyroid hormone in hemodialysis patients.     

Effect of Alfacalcidol Therapy on the Survival of Chronic Hemodialysis Patients

The aim of this study was to determine the relationship between alfacalcidol therapy and the outcomes of chronic hemodialysis (HD) patients. We collected demographic and clinical baseline data from 190 prevalent HD patients in a regional Japanese cohort. A 5‐year survival analysis was performed according to whether the patients were receiving calcitriol analog therapy. Alfacalcidol therapy at a mean dose of 5.2 ± 1.8 µg/week was performed in 89 (46.8%) of the 190 patients. We recorded 38 deaths during the follow‐up period, including 19 deaths from cardiovascular events. A Kaplan–Meier analysis demonstrated that the alfacalcidol users had a significantly lower rate of all‐cause mortality and cardiovascular mortality than the non‐users. According to a multivariate Cox proportional hazards model, in addition to the use of alfacalcidol (HR=0.347 [0.155–0.714]; P = 0.0035), serum CRP levels (HR= 1.746 [1.184–2.442]; P = 0.0071) and non‐HDL‐cholesterol levels (HR=1.012 [1.001–1.022]; P = 0.0267) were identified as independent predictors of all‐cause mortality, and the presence of diabetes mellitus (HR=3.720 [1.182–12.398]; P = 0.0246) was identified as an independent predictor of cardiovascular mortality. These findings suggest that low‐dose alfacalcidol therapy provides a survival advantage to chronic HD patients.     

金乌骨痛胶囊联合阿法骨化醇治疗膝骨关节炎合并骨质疏松症的临床疗效观察

目的:观察和评价金乌骨通胶囊联合阿法骨化醇对于膝骨关节炎合并骨质疏松症患者的临床疗效。方法:入组60例经临床X线、骨密度和临床病史确诊的患者,随机分成两组,治疗组口服金乌骨通胶囊+法能,对照组口服英太青+法能,治疗8周后,通过WOMAC的评分进行疗效评估,同时测定25-OH-VD3和骨转换指标(骨钙素OC、I型原胶原N-端前肽PINP和血清I型胶原交联C-末端肽S-CTX),了解对骨代谢改善情况。结果:治疗8周后,两组的膝关节疼痛均有减轻(P<0.01),日常活动的难度明显降低(P<0.01),膝关节晨僵及僵硬度有减轻(P<0.05)。两组间比较,治疗组均更胜一筹(P<0.05~0.01)。血清中25-OH-VD3恢复到正常51.5nmo/L以上,治疗组中血清骨钙素较治疗前和对照组均有升高(P<0.05)。结论:金乌骨通胶囊联合阿法骨化醇对膝骨关节炎合并骨质疏松症患者的治疗,可以达到缓解疼痛,提高膝关节及肢体的活动度,同时改善生活质量,能长期应用,同时亦能增加骨钙素,提高骨骼成骨功能,纠正骨代谢的失衡。     

阿法骨化醇对大剂量糖皮质激素治疗肾小球疾病所致的骨质疏松的影响

目的：观察阿法骨化醇联合钙剂对肾脏病患者发生糖皮质激素性骨质疏松的预防作用。方法：28例病人随机分为治疗组16例,阿法骨化醇1μg日一次口服和碳酸钙750 mg日三次口服;对照组12例,碳酸钙750 mg日三次口服。治疗前及以后每3个月检查血清白蛋白、钙、磷、24小时尿蛋白定量、甲状旁腺素,腰椎和股骨颈骨密度,观察6个月。结果：两组患者腰椎和股骨颈骨密度均呈下降趋势,治疗6个月时,治疗组骨密度高于对照组（腰椎0.967±0.105,0.896±0.131,P〈0.05;股骨颈1.078±0.124,0.925±0.107,P〈0.05）,对照组骨密度较治疗前明显下降。结论：阿法骨化醇合用钙剂对预防慢性肾脏病患者发生糖皮质激素性骨质疏松是安全有效的药物。     

Can the fast bone loss in osteoporotic and osteopenic patients be stopped with active vitamin D metabolites?

The aim of this study was to evaluate whether fast trabecular bone loss in osteoporotic and osteopenic patients can effectively be treated with active vitamin D metabolites. Thirty-one osteoporotic and osteopenic patients were monitored between 4 and 22 months before and between 8 and 18 months during the treatment. Fast bone losers were designated as osteoporotic or osteopenic patients with a loss of trabecular bone density in the radius of 3% or more calculated for 1 year. For this differentiation, the high precise peripheral quantitative computed tomography system (DENSISCAN 1000) was used (reproducability 0.3% in mixed collectives). The pretreatment loss and the ``gain' under treatment with active vitamin D metabolites was calculated for 1 year. The treatment consisted of either 0.5 μg calcitriol daily or 1 μg of alfacalcidol daily. Before treatment, the trabecular bone loss in the radius/year was −6.6 ± 0.5% (mean ± SEM). After treatment with vitamin D metabolites, the trabecular bone gain in the radius/year was 0.01 ± 0.6% (mean ± SEM). The difference was highly significant (P < 0.001). In contrast to this, the loss of cortical bone density before treatment was −1.8 ± 0.3% (mean ± SEM) and the reduced loss after treatment −0.2 ± 0.4% (mean ± SEM), both values calculated for 1 year. This difference was less significant (P < 0.05). This study shows that the treatment with active vitamin D metabolites is very effective in slowing fast trabecular bone loss in osteoporotic and osteopenic patients.     

Intermittent intravenous ibandronate injections reduce vertebral fracture risk in corticosteroid-induced osteoporosis: results from a long-term comparative study

Despite its well-known benefits, chronic corticosteroid therapy causes osteoporotic fractures in approximately 30–50% of patients treated. To prevent the occurrence of these fractures, treatment with oral bisphosphonates is recommended. However, current oral bisphosphonates, which are given either daily or weekly, are associated with stringent, inconvenient dosing guidelines. Less frequent dosing may provide greater acceptability. The objective of this study was to investigate the efficacy and safety of ibandronate, a highly potent nitrogen-containing bisphosphonate, when given by intravenous (i.v.) injection every 3 months in men and women with established corticosteroid-induced osteoporosis (CIO; lumbar spine [L2-L4] bone mineral density [BMD] T-score –2.5). A total of 115 participants were assigned to receive daily calcium supplements (500 mg) plus either ibandronate (2 mg) injections every 3 months or daily oral alfacalcidol (1 g), for 3 years. Intermittent i.v. ibandronate injections produced significantly greater increases in mean BMD at the lumbar spine (13.3% versus 2.6%, respectively; p<0.001), and femoral neck (5.2% versus 1.9%, respectively; p<0.001) versus daily oral alfacalcidol, after 3 years, relative to baseline. This study was not statistically powered to show a difference between the groups with respect to fracture incidence. Nevertheless, after 36 months, the frequency of patients with new vertebral fractures was significantly lower in the patients receiving ibandronate relative to those taking alfacalcidol (8.6% versus 22.8%, respectively; p=0.043). This is the first time that significant vertebral fracture reduction has been demonstrated with an i.v. bisphosphonate in CIO. Patients treated with i.v. ibandronate injections also experienced less back pain (p<0.001) and less height loss (p=0.001) than those receiving oral alfacalcidol. Both regimens were well tolerated. In conclusion, intermittent i.v. ibandronate injections are efficacious, well-tolerated, and convenient, and promise to offer physicians an important therapeutic advance in the management of osteoporosis.     

Effect of alendronate on glucocorticoid-induced osteoporosis in Japanese women with systemic autoimmune diseases: versus alfacalcidol

Glucocorticoids-induced osteoporosis is a serious problem for patients with systemic autoimmune disease requiring relatively long-term glucocorticoid treatment. Effectiveness of alendronate for the prevention of glucocorticoids-induced osteoporosis was evaluated in comparison with that of alfacalcidol in Japanese women with autoimmune disease excluding rheumatoid arthritis. Loss of bone mass was evaluated with bone mineral density (BMD) of lumber vertebrae, bone resorption was with urinary N-telopeptide for type I collagen (NTX), and bone formation was with serum bone-specific alkaline phosphatase (B-ALP). A total of 33 patients who were treated with oral glucocorticoids (>/=5 mg/day of prednisolone equivalence) for more than 6 months were randomized into two groups; alendronate group (n = 17) received 5 mg/day of alendronate, and alfacalcidol group (n = 16) received 1.0 mug/day of alfacalcidol for 24 months with glucocorticoids. The dose of alendronate was the maximal dose approved in Japan. BMD had tendency to decrease with alfacalcidol, while increase with alendronate. The difference in BMD change between the two groups was significant by 4.3% at 18 months and by 4.2% at 24 months (both P < 0.05). Bone resorption was significantly reduced only with alendronate; NTX was decreased by 28 to 35% at 6 to 24 months (P < 0.05), but not changed with alfacalcidol at 24 months. The bone formation was found to be unchanged according to the B-ALP measured between the two groups. In conclusion, the treatment of 5 mg alendronate daily is more effective than alfacalcidol for preventing the glucocorticoid-induced osteoporosis by the mechanism of reducing bone resorption in Japanese women with systemic autoimmune disease.