阿法骨化醇胶丸联合碳酸钙片治疗慢性肾衰继发甲状旁腺功能亢进的疗效观察

目的:观察阿法骨化醇胶丸联合碳酸钙片治疗慢性肾衰继发甲状旁腺功能亢进(SHPT)的疗效。方法:将55例慢性肾衰继发SHPT患者分为透析组(28例)和非透析组(27例),均在服用阿法骨化醇胶丸的同时加用碳酸钙片,连用3mo。观察治疗前、后血钙(Ca2+)、磷(P3-)、甲状旁腺激素(PTH)、碱性磷酸酶(AKP)、肌酐(Cr)的变化。结果:2组治疗后血Ca2+均明显升高(P<0.05),血PTH均明显下降(P<0.01)。结论:阿法骨化醇胶丸联合碳酸钙片治疗慢性肾衰继发SHPT早期患者安全、有效、经济。     

阿仑膦酸钠与阿法骨化醇治疗老年性骨质疏松症的疗效比较

目的比较阿仑膦酸钠片、阿法骨化醇胶囊治疗老年性骨质疏松症的临床疗效及安全性。方法将56例老年性骨质疏松症患者,采取随机法分成2组。观察组给予口服阿仑膦酸钠片70 mg,每周1次;对照组给予口服阿法骨化醇胶囊0.5μg,每日1次;同时2组患者每天均服用钙剂600 mg,连续治疗6个月。测定治疗前后骨密度(BMD)、生化指标,采取VAS法评价治疗前后疼痛改善情况等。结果治疗后观察组的L2、L3、L4、股骨颈的骨密度值分别增加了3.61%、4.76%、3.66%和5.06%;观察组的骨密度值分别增加了3.57%、4.71%、3.61%和5.0%,2组间差异无统计学意义(p>0.05)。治疗后观察组改善疼痛症状优于对照组(p<0.05)。结论两种药物治疗老年性骨质疏松症具有良好的临床疗效,能显著增加患者骨密度,缓解疼痛程度;但阿仑膦酸钠片服药方便,患者顺从性较好,较适宜在临床推广应用。     

Randomized controlled trial of alfacalcidol supplementation for the reduction of hypocalcemia after total thyroidectomy

BackgroundThe aim of this study was to evaluate the effect of perioperative alfacalcidol on postoperative hypocalcemia after total thyroidectomy.MethodsA total of 219 patients scheduled for total thyroidectomy were randomized into groups not receiving (group A) or receiving (group B) perioperative alfacalcidol. Postoperative hypocalcemia was compared between groups on postoperative day (POD) 1 and POD2. Patients with hypocalcemia (<2.00 mmol/L) received oral calcium supplementation. Calcium and vitamin D levels were measured at 5-week and 6-month follow-ups.ResultsThe incidence of symptomatic hypocalcemia was significantly lower in group A (P = .02), whereas similarly low levels of calcemia were observed in both groups on POD1 (37% and 30%, respectively; P = not significant) and persisted on POD2 (14% and 6%, respectively; P = not significant). Patients with severe hypocalcemia (<1.90 mmol/L) showed faster recovery in group A compared with group B (6% vs 1%, P = .04). At 5 weeks, calcium and vitamin D levels were similar between the groups. Six months after surgery, 4% (group A) versus 0% (group B) of subjects exhibited permanent hypoparathyroidism (P = .04).ConclusionsAlthough the treatment did not correct vitamin D deficiency, perioperative alfacalcidol uptake resulted in decreased transient hypocalcemia and related symptoms in patients undergoing total thyroidectomy.     

Vitamin D Analogs Versus Native Vitamin D in Preventing Bone Loss and Osteoporosis-Related Fractures: A Comparative Meta-analysis

It has been suggested that early postmenopausal women and patients treated with steroids should receive preventive therapy (calcium, vitamin D, vitamin D analogs, estrogens, or bisphosphonates) to preserve their bone mineral density (BMD) and to avoid fragility fractures. We designed the present study to compare the effects of native vitamin D to its hydroxylated analogs alfacalcidol 1-(OH)D and calcitriol 1,25(OH)₂D. All randomized, controlled, double-blinded trials comparing oral native vitamin D and its analogs, alfacalcidol or calcitriol, to placebo or head-to-head trials in primary or corticosteroids-induced osteoporosis were included in the meta-analysis. Sources included the Cochrane Controlled Trials Register, EMBASE, MEDLINE, and a hand search of abstracts and references lists. The study period January 1985 to January 2003. Data were abstracted by two investigators, and methodological quality was assessed in a similar manner. Heterogeneity was extensively investigated. Results were expressed as effect-size (ES) for bone loss and as rate difference (RD) for fracture while allocated to active treatment or control. Publication bias was investigated. Fourteen studies of native vitamin D, nine of alfacalcidol, and ten of calcitriol fit the inclusion criteria. The two vitamin D analogs appeared to exert a higher preventive effect on bone loss and fracture rates in patients not exposed to glucocorticoids. With respect to BMD, vitamin D analogs versus placebo studies had an ES of 0.36 (P < 0.0001), whereas native vitamin D versus placebo had an ES of 0.17 (P = 0.0005), the interclass difference being highly significant (ANOVA-1, P < 0.05). When restricted to the lumbar spine, this intertreatment difference remained significant: ES = 0.43 (P = 0.0002) for vitamin D analogs and ES = 0.21 (P = 0.001) for native vitamin D (analysis of variance [ANOVA-1], P = 0.047). There were no significant differences regarding their efficacies on other measurement sites (ANOVA-1, P = 0.36). When comparing the adjusted global relative risks for fracture when allocated to vitamin D analogs or native vitamin D, alfacalcidol and calcitriol provided a more marked preventive efficacy against fractures: RD = 10% (95% Confidence interval [CI-2] to 17) compared to RD = 2% (95% CI, 1 to 2), respectively. The analysis of the spinal and nonspinal showed that fracture rates differed between the two classes, thereby confirming the benefits of vitamin D analogs, with significant 13.4% (95% CI 7.7 to 19.8) and. 6% (95% CI 1 to 12) lower fracture rates for vitamin D analogs, respectively. In patients receiving corticosteroid therapy, both treatments provided similar global ESs for BMD: ES = 0.38 for vitamin D analogs and ES = 0.41 for native vitamin D (ANOVA-1, P = 0.88). When restriced to spinal BMD, D analogs provided significant effects, whereas native vitamin D did not: ES = 0.43 (P < 0.0001) and ES = 0.33 (P = 0.21), respectively. The intertreatment difference was nonsignificant (ANOVA-1, P = 0.52). Neither D analogs for native vitamin D significantly prevented fractures in this subcategory of patients: RD = 2.6 (95%CI, –9.5 to 4.3) and RD = 6.4 (95%CI, –2.3 to 10), respectively. In head-to-head studies comparing D analogs and native vitamin D in patients receiving corticosteroids, significant effects favoring D analogs were found for femoral neck BMD: ES = 0.31 at P = 0.02 and spinal fractures: RD = 15% (95%CI, 6.5 to 25). Publication bias was not significant. Our analysis demonstrates a superiority of the D analogs atfacalcidol and calcitriol in preventing bone loss and spinal fractures in primary osteoporosis, including postmenopausal women. In corticosteroid-induced osteoporosis, the efficacy of D analogs differed depending on the comparative approach: indirect comparisons led to nonsignificant differences, whereas direct comparison did provide significant differences. In this setting, D analogs seem to prevent spinal fractures to a greater extent than do native vitamin D, but this assumption should be confirmed on a comprehensive basis in multiarm studies including an inactive comparator.     

Intravenous Alfacalcidol Once Versus Twice or Thrice Weekly in Hemodialysis Patients

Secondary hyperparathyroidism remains a serious problem in hemodialysis patients. The use of vitamin D analogs still constitutes a basis for its treatment. This study was carried out to evaluate the efficacy of intravenous administration of alfacalcidol once versus twice or thrice weekly in hemodialysis patients with secondary hyperparathyroidism. Twenty‐nine end‐stage renal disease patients maintained on hemodialysis for more than one year were included in this prospective study after signing the consent. These patients with secondary hyperparathyroidism had been on intravenous alfacalcidol twice or thrice per week and were followed up to 4 months (stage 1). Then they were shifted to intravenous alfacalcidol once weekly starting with the last total weekly intravenous dose for another 4 months (stage 2). The dose of alfacalcidol was adjusted according to intact parathyroid hormone, serum calcium and phosphorus levels, and calcium‐phosphorus product. Intact parathyroid hormone, calcium, phosphorus, calcium‐phosphorus product were measured monthly. Parathyroid ultrasound was done as a baseline and then repeated at the end of stage 1 and stage 2. The intact parathyroid hormone was reduced from 49.72 ± 2.72 pmol/L (mean ± standard error of the mean [SEM] during stage 1 to 42.13 ± 2.15 pmol/L during stage 2 (P = 0.005). Dose of alfacalcidol was reduced from 18.80 ± 1.15 µg/month (mean ± SEM) in stage 1 to 15.18 ± 1.27 µg/month in stage 2 (P = 0.008), and consequently the cost of alfacalcidol was reduced from 21.05 ± 1.25 US$/month (mean ± SEM) during stage 1 to 16.87 ± 1.40 US$/month during stage 2 (P = 0.008). Although the phosphorus level increased from 1.56 ± 0.36 mmol/L (mean ± SD) in stage 1 to 1.70 ± 0.46 mmol/ L in stage 2 (P = 0.003), and calcium‐phosphorus product increased from 3.48 ± 0.82 mmol²/L² (mean ± SD) in stage 1 to 3.76 ± 1.00 mmol²/L² in stage 2 (P = 0.017), they remained in the target levels recommended by the Kidney Disease Outcomes Quality Initiative guidelines. No serious effects were observed during stage 1 and stage 2, respectively. Intravenous alfacalcidol once weekly is effective, safe and less costly in suppressing intact parathyroid hormone compared to twice or thrice weekly administration in chronic hemodialysis patients.     

Effects of 5-year treatment with elcatonin and alfacalcidol on lumbar bone mineral density and the incidence of vertebral fractures in postmenopausal women with osteoporosis: a retrospective study

 The purpose of this retrospective study was to compare the effects of long-term treatment (5 years) with elcatonin and alfacalcidol on bone mineral density (BMD) and the incidence of vertebral fractures in postmenopausal women with osteoporosis. Fifty-six osteoporotic women, more than 5 years after menopause and 58–79 years of age, were enrolled in the study and allocated to an elcatonin treatment group (20 units IM, weekly; n = 30) or an alfacalcidol treatment group (1 μg/day, daily; n = 26). BMD of the lumbar spine (L2-L4) was measured by dual energy X-ray absorptiometry at baseline and every year for 5 years. There were no significant differences in age, body mass index, years since menopause, BMD, or number of prevalent vertebral fractures at baseline between the two groups. One-way analysis of variance with repeated measurements showed no significant longitudinal changes in BMD in either group, suggesting that both treatments sustained the BMD over 5 years. Two-way analysis of variance with repeated measurements also showed no significant differences in longitudinal changes in BMD between the two groups, suggesting that the effects of the two treatments on BMD were similar. However, the number of incident vertebral fractures per patient was significantly lower in the alfacalcidol treatment group than in the elcatonin treatment group (0.80 ± 1.19 and 2.08 ± 2.73, respectively; P < 0.05). These findings indicate that both treatments appeared to sustain lumbar BMD similarly over a 5-year period in postmenopausal women with osteoporosis, but alfacalcidol treatment may be superior to elcatonin treatment regarding the incidence of vertebral fractures. Further study with prospective observations are needed to confirm the results of the present study. Received: April 2, 2002 / Accepted: July 13, 2002 Offprint requests to: J. Iwamoto     

A Double-Masked Multicenter Comparative Study Between Alendronate and Alfacalcidol in Japanese Patients with Osteoporosis

To evaluate the efficacy and safety of alendronate, a double-masked, active (alfacalcidol) controlled comparative study for 48 weeks was carried out in a total of 210 Japanese patients with osteoporosis. The doses of alendronate and alfacalcidol were 5 mg/day and 1 μg/day, respectively. The lumbar bone mineral density (LBMD) values observed at 12, 24, 36 and 48 weeks after the initiation of alendronate treatment were 3.53 ± 0.53%, 5.37 ± 0.62%, 5.87 ± 0.74% and 6.21 ± 0.59% (mean ± SE), respectively, higher than the baseline value. Corresponding values in the alfacalcidol group were 1.50 ± 0.43%, 0.69 ± 0.63%, 1.12 ± 0.60% and 1.36 ± 0.63%, respectively. There was a significant difference between the two groups at each time point (p<0.05 or p<0.001). The bone turnover markers were depressed during treatment in the alendronate group: −32.2% for alkaline phosphatase, −53.7% for N-terminal osteocalcin and −45.0% for urinary deoxypyridinoline compared with the corresponding baseline values. On the contrary, no notable changes in these parameters were observed in the alfacalcidol group. Treatment with alendronate caused a transient decrease in serum calcium concentrations associated with an increase in the serum level of intact parathyroid hormone. In contrast, treatment with alfacalcidol resulted in a tendency of these parameters to change in the opposite direction. No difference in fracture incidence between the two groups was observed. The overall safety of alendronate was comparable to that of alfacalcidol. In conclusion, although it was a relatively short-term study of 48 weeks, the results of the present study indicate that alendronate at the daily dose of 5 mg was effective in increasing LBMD and that no serious drug-related adverse events were observed in the alendronate-treated patients. Alendronate is more efficacious than alfacalcidol in increasing bone mineral density, although the mechanisms of the actions of the two drugs are apparently different. Received: 2 July 1998 / Accepted: 4 February 1999     

A comparison of the effects of alfacalcidol treatment and vitamin D2 supplementation on calcium absorption in elderly women with vertebral fractures

Although vitamin D supplementation in the frail elderly improves calcium absorption, suppresses parathyroid hormone, decreases bone loss and reduces the risk of fractures, such treatment may be ineffective in patients with vertebral osteoporosis, because of impaired vitamin D metabolism or resistance to the action of vitamin D metabolites on the bowel. We have therefore performed a randomized, single masked study comparing the effects of alfacalcidol treatment (0.25 µg twice daily) and vitamin D₂ supplementation (500-1000 units daily) on calcium absorption and bone turnover in 46 elderly women (median age 69 years, range 64–79 years) with radiological evidence of vertebral fractures. Serum 25-hydroxyvitamin D increased significantly after 3 and 6 months of treatment with vitamin D₂ (p<0.001), but was unchanged in the group receiving alfacalcidol. Serum 1,25-dihydroxyvitamin D did not change significantly in either group over the study period. Fractional⁴⁵Ca absorption increased after 3 months of treatment with alfacalcidol (p<0.05), but was unchanged with vitamin D₂. There was also a reduction in plasma intact parathyroid hormone and serum alkaline phosphatase after 6 months of treatment with alfacalcidol (p<0.05) which was not seen in the group receiving vitamin D₂. Our study shows that vitamin D₂ supplementation is ineffective in stimulating calcium absorption in elderly women with vertebral osteoporosis. By increasing calcium absorption in such patients, alfacalcidol may prove more effective than vitamin D in the management of vertebral osteoporosis.     

Improving the outcome of established therapies for osteoporosis by adding the active D-hormone analog alfacalcidol

While in other chronic diseases combined treatment regimens are the rule there is a lack of reported experience or study data on combining different specific drugs to treat osteoporosis. Significant differences in the mode of action (MOA) of the substances to be combined may be important for achieving optimal therapeutic results. Recognising that today bisphosphonates are the leading therapy for osteoporosis we suggest that the active D-hormone analog alfacalcidol with its completely different mechanisms of action could be an interesting combination to improve the therapeutic outcome of the pure antiresoptive action of bisphosphonates. Alfacalcidol is activated by the enzyme 25-hydroxylase in the liver for systemic and in osteoblasts for local D-hormone actions. It possesses a unique pattern of pleiotropic effects on, e.g. gut, bone, pararthyroids, muscle and brain. Alfacalcidol is superior to plain vitamin D (cholecalciferol) because the final kidney activation of the latter is regulated by a negative feedback mechanism. In vitamin D replete patients or patients with impaired kidney function no increased D-hormone action at the target tissues can be achieved. Animal studies and several trials in humans with alendronate plus calcitriol or alfacalcidol proved that the combination induced significantly higher increases of bone mineral density (BMD) than the respective mono-therapies. The results of the 2-year AAC-trial from our group indicate that the combination alendronate and alfacalcidol is also superior in terms of falls, fractures and back pain. From the review of the literature and the own new results we conclude that this combined therapeutic regimen is a very promising option for treating established osteoporosis and propose a differentiated use of alfacalcidol alone or the combination with alendronate in different stages and clinical situations of osteoporosis.