Short-term Effects of Alfacalcidol on Hospital Length of Stay in Patients Undergoing Valve Replacement Surgery: A Randomized Clinical Trial

PurposeVitamin D deficiency is highly prevalent in critically ill patients, and has been associated with more prolonged length of hospital stay and poor prognosis. Patients undergoing open-heart surgery are at higher risk due to the associated life-threatening postoperative complications. This study investigated the effect of alfacalcidol treatment on the length of hospital stay in patients undergoing valve-replacement surgery.MethodsThis single-center, randomized, open-label, controlled trial was conducted at El-Demerdash Cardiac Academy Hospital (Cairo, Egypt), from April 2017 to January 2018. This study included adult patients undergoing valve-replacement surgery who were randomized to the intervention group (n = 47; alfacalcidol 2 μg/d started 48 h before surgery and continued throughout the hospital stay) or to the control group (n = 42). The primary end points were lengths of stay (LOS) in the intensive care unit (ICU) and in the hospital. Secondary end points were the prevalence of postoperative hospital-acquired infections, cardiac complications, and in-hospital mortality.FindingsA total of 86 patients were included in the final analysis, with 51 (59.3%) being vitamin D deficient on hospital admission. Treatment with alfacalcidol was associated with a statistically significant decrease in ICU LOS (hazard ratio = 1.61; 95% CI, 1.77–2.81; P = 0.041) and hospital LOS (hazard ratio = 1.63; 95% CI, 1.04–2.55; P = 0.034). Treated patients had a significantly lower postoperative infection rate than did the control group (35.5% vs 56.1%; P = 0.017). The median epinephrine dose was lower in the intervention group compared to that in the control group (5.9 vs 8.2 mg; P = 0.019). The rate of in-hospital mortality was not significantly different between the 2 groups.ImplicationsEarly treatment with 2 μg of alfacalcidol in patients undergoing valve-replacement surgery is promising and well tolerated. This effect may be attributed to its immunomodulatory and cardioprotective mechanisms. ClinicalTrials.gov identifier: NCT04085770.     

Pharmacotherapy of osteoporosis in postmenopausal women: focus on safety

The therapy of osteoporosis has made enormous strides in the last decade. There is now a range of interventions, each with its pros and cons. Calcium and vitamin D supplementation remain the foundation and have few safety issues. Bisphosphonates are widely used, though gastrointestinal tolerance is a problem with some oral preparations. Intravenous administration may circumvent this, although this introduces the smaller problem of acute phase reactions. The side effect profile of hormone replacement therapy (HRT) is still being delineated after 40 years of use, with substantial new information expected in the next few years. This will clarify its place in the medical management of the menopause. Raloxifene appears to have a superior safety profile to HRT, though its efficacy on bone may be less. While none of these options is suitable for everyone, the range of available therapies does mean that most patients can find an intervention that is effective and acceptable.     

Alfacalcidol reduces accelerated bone turnover in elderly women with osteoporosis

To evaluate the effects of alfacalcidol on bone turnover in elderly women with osteoporosis, an open-label, prospective, calcium-controlled study was conducted. A total of 80 patients with osteoporosis were divided into two groups: the control group, group C (mean age, 78.0 years), in which patients were given calcium, and group D (mean age, 77.4 years), in which the patients were given alfacalcidol 1µg/day together with calcium for 6 months. Calcium regulation, lumbar bone mineral density (LBMD), and markers for bone turnover were assessed. A significant increase in urinary calcium/creatinine ratio (90% increase from baseline at 3 months; P = 0.0083, and 60% at 6 months; P = 0.0091) and a significant decrease in serum parathyroid hormone (30% decrease from baseline at 6 months; P < 0.0001) was observed in group D compared with the corresponding changes in group C. Significant decreases of bone resorption markers (deoxypyridinoline and N-telopeptide) at 6 months (about 15% decrease from the baseline values) were observed in group D compared with the corresponding changes in group C. The changes in bone formation markers (bone-derived alkaline phosphatase and osteocalcin) in group D were significantly different at 6 months (–21.5%; P = 0.0047 and –13.4%; P = 0.0032, respectively) from the values in group C. The magnitudes of the decrease in bone turnover markers were highly correlated with the corresponding baseline values, suggesting that alfacalcidol treatment effectively reduces bone turnover in patients with high bone turnover rates. The LBMD in group D increased by 1.7% and that in group C decreased by 1.6% (P = 0.0384). The changes in calcium metabolism and LBMD were in good agreement with those in previous reports. Although the changes in bone turnover markers in group D were slight, significant reduction in bone turnover with alfacalcidol treatment, together with the change in calcium metabolism, may account for the effects of alfacalcidol on BMD and on fracture prevention reported previously. In conclusion, alfacalcidol reduces bone turnover in elderly women with high-bone-turnover osteoporosis, and it may have beneficial effects on bone.     

益骨饮治疗绝经后骨质疏松症的临床观察

[目的]观察中药制剂益骨饮治疗绝经后骨质疏松症的临床疗效。[方法]将93例绝经后骨质疏松症随机分为两组，A组47例内服中药益骨饮，B组46例采用西药“钙＋D”作为对照组，2个月为1个疗程。治疗前后检测血、尿常规，肝、肾功能，血糖、钙、磷、雌激素及骨密度等指标。[结果]治疗后两组间的碱性磷酸酶、雌二醇、睾酮及骨密度均略有上升；疼痛NRS指数、尿钙／肌酐比值也均有相对降低趋势；中药组总有效率达84．4％，对照组总有效率为77．7％，中药组总体疗效优于对照组。[结论]中药益骨饮对绝经后骨质疏松症有较好的防治作用。     

阿法骨化醇增加伊班膦酸钠治疗绝经后骨质疏松症的疗效

目的探索阿法骨化醇(alfacalcidol,ALF)在伊班膦酸钠(ibandronate,IBN)治疗绝经后骨质疏松症期间的作用。方法选取2015年7月至2017年6月在我院就诊的56例绝经后骨质疏松症患者作为研究对象,随机分为IBN组和IBN/ALF组;IBN组给予IBN治疗,IBN/ALF给予IBN联合ALF,治疗为期12个月。观察治疗前后两组女性骨密度及骨代谢指标的改变。结果与治疗前相比,3个月后两组骨转换指标均显著降低(P0.05)。IBN/ALF组血清1型前胶原氨基末端前肽(N-propeptide of type 1 collagen,P1NP)、抗酒石酸酸性磷酸酶-5b(tartrate-resistant acid phosphatase-5b,TRACP-5b)和尿I型胶原N末端交联(urinary type I collagen crosslinked amino terminal peptide,NTX)水平明显低于IBN组(P0.05)。IBN/ALF组6个月和IBN组12个月时腰椎(L_(1～4))骨密度(bone mineral density,BMD)均显著增加(P0.05)。12个月时IBN/ALF组(4.7%)的L-BMD显著高于IBN组(2.9%)。IBN/ALF组的全髋(H)-BMD从6个月开始显著增加,而IBN组的H-BMD改善不明显。IBN/ALF组(4.3%)的H-BMD在12个月时显著高于IBN组(2.7%)。结论 ALF有助于IBN治疗绝经后骨质疏松症的疗效。     

阿法骨化醇冲击疗法联合血液灌流治疗维持性血液透析患者皮肤瘙痒25例

目的 观察阿法骨化醇冲击疗法联合血液灌流治疗维持性血液透析患者皮肤瘙痒的疗效.方法 选取医院血透室维持性血液透析患者50例,均有不同程度的皮肤瘙痒.随机分为两组,治疗组给予阿法骨化醇冲击疗法联合血液灌流,对照组仅给予血液灌流,治疗4周.观察两组治疗前后尿素氮(BUN)、血清肌酐(Scr)、继发性甲状旁腺激素(iPTH)、血钙(Ca2+)、血磷(P3+)的变化.结果 两组治疗结束后皮肤瘙痒均有不同程度改善;治疗组治疗前后iPTH和P3+差异有显著统计学意义(P<0.01);对照组治疗前后iPTH和P3+差异有统计学意义(P<0.05);两组治疗前后BUN,Scr,Ca2+变化不明显(P>0.05).结论 阿法骨化醇冲击疗法联合血液灌流治疗维持性血液透析患者皮肤瘙痒疗效显著,其机制可能与清除iPTH和P3+有关.     

Alfacalcidol treatment increases bone mass from anticatabolic and anabolic effects on cancellous and cortical bone in intact female rats

It has been reported that alfacalcidol had an anticatabolic and anabolic effect on bone in ovariectomized and aged male rat models, but this has not been tested on intact female rats. The current study was to determine the effects of alfacalcidol on cancellous and cortical bone in intact female rats with or without exercise. Seventy-four, 8.5-month-old, intact female rats were orally treated with 0, 0.005, 0.025, 0.05, or 0.1 microg/kg alfacalcidol alone or in combination with raised cage (RC) exercise for 3 months. In vivo peripheral quantitative computerized tomography (pQCT) of the proximal tibial metaphyses (PTM) and ex vivo histomorphometric analyses of the PTM and tibial shaft (TX) were performed. Only the 0.1 microg alfacalcidol/kg dose proved to be anabolic. pQCT analysis showed that this dose increased total and cortical bone mineral content and density and trabecular bone mineral density. Histomorphometrically, it induced an anabolic response by increased trabecular mass and microarchitecture from stimulated cancellous bone and bone bouton formations, and suppressed bone resorption more than bone formation on the trabecular and endocortical surfaces, to produce a positive bone balance. A positive correlation between trabecular connectivity and bone bouton numbers occurred. These findings suggest alfacalcidol treatment augments bone mass by increased cancellous bone mass and improved trabecular architecture through its anticatabolic and anabolic properties in the intact adult female rat. Last, raised cage exercise alone or the combination of raised cage and alfacalcidol was no more effective than alfacalcidol alone.     

Systematic review of the benefits and harms of calcitriol and alfacalcidol for fractures and falls

Our objective was to conduct a systematic review on the benefits and harms of calcitriol and alfacalcidol in the reduction of fracture and fall risk. Randomized controlled trials (RCTs) comparing these agents to placebo or calcium and reporting fracture and fall incidence were retrieved from MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials. Two reviewers independently determined study eligibility, assessed trial quality, and extracted data. Twenty-three RCTs were included (2139 participants), and 16 trials had sufficient data for meta-analysis. Vertebral fractures were not significantly reduced based on the combined results of 13 trials; however, subgroup analyses demonstrated a significant reduction with alfacalcidol [odds ratio (OR) = 0.50, 95% confidence interval (CI), 0.25–0.98], but not with calcitriol. There was a significant reduction in nonvertebral fractures (six trials, OR = 0.51, 95% CI, 0.30–0.88), and falls (two trials, OR = 0.66, 95% CI, 0.44–0.98). There was an increased risk of hypercalcemia (OR = 3.63, 95% CI, 1.51–8.73) and a trend toward an increased risk of hypercalciuria. There is evidence to suggest that these agents may reduce the incidence of nonvertebral fractures and falls; however, their benefit on vertebral fracture reduction may depend on the type of active vitamin D. Hypercalcemia and hypercalciuria are potential side effects.     

Effect of 18 months of treatment with alfacalcidol on bone in patients with mild to moderate chronic renal failure.

BACKGROUND: The bone abnormalities that lead to symptomatic renal osteodystrophy commence early in the course of renal failure, but the optimal time to start treatment needs clarifying. The present study examined the effect of alfacalcidol treatment on bone metabolism and bone density in patients with pre-dialysis chronic renal failure (CRF) in a prospective, randomized, placebo-controlled double blind design. METHODS: Repetitive measures of bone mineral density (BMD) estimated by dual energy X-ray absorptiometry and plasma levels of biochemical markers of bone turnover [osteocalcin, bone alkaline phosphatase, propeptide of type-I collagen (PICP) and telopeptide of type-I collagen] and parameters of calcium homeostasis were performed in 36 patients with a glomerular filtration rate (GFR) of 6-60 ml/min. RESULTS: A significant difference in BMD between the treatment groups in favour of the alfacalcidol-treated patients was found in the spine (4.2%), the femoral neck (4.9%) and the total femur (3.0%) (P<0.05). In the alfacalcidol group, plasma levels of parathyroid hormone 1-84 decreased from baseline values by 47+/-9%, and p-osteocalcin and bone alkaline phosphatase decreased by 24+/-9% and 48+/-8%, respectively (P<0.05). In the placebo group, PICP increased by 32+/-26% (P<0.05). No significant changes were found in plasma levels of vitamin D metabolites. GFR decreased significantly from baseline values in the alfacalcidol group (by 28+/-4 ml/min) and in the placebo group (by 26+/-5 ml/min) (P<0.05), with no difference being detected between the groups. CONCLUSIONS: Long-term treatment with alfacalcidol is safe and might be beneficial for the preservation of bone mass in the pre-dialysis stages of CRF, most likely through a reduction in bone turnover as estimated from the changes of the biochemical bone markers.     

Randomized trial comparing pulse calcitriol and alfacalcidol for the treatment of secondary hyperparathyroidism in haemodialysis patients

Aim: Calcitriol and alfacalcidol are used extensively for the treatment of secondary hyperparathyroidism. Unfortunately, there is limited published data comparing the efficacy and tolerability of both active vitamin D sterols. This study was undertaken to determine whether calcitriol provides a therapeutic advantage to alfacalcidol. Methods: This was a randomized, active controlled study. Patients with intact parathyroid hormone (iPTH) >32 pmol/L were randomized to receive orally calcitriol or alfacalcidol after each haemodialysis for up to 24 weeks. Reduction of PTH, changes of plasma albumin‐corrected calcium and phosphorus were analysed. The initial dose of alfacalcidol was twice that of calcitriol. Results: Sixteen patients were randomized into each group. At baseline, plasma albumin‐corrected calcium, phosphorus and PTH were no different between groups. At 24 weeks, PTH changes were ?50.8 ± 31.8% and ?49.4 ± 32.5% from the baseline in the calcitriol and alfacalcidol groups, respectively (P = 0.91). The patients who achieved target PTH of 16–32 pmol/L were 82% in the calcitriol and 67% in the alfacalcidol group (P = 0.44). Plasma albumin‐corrected calcium and phosphorus were not significantly different but showed trends toward gradually increasing from baseline in both groups (calcium, 6.0 ± 7.2% vs 10.9 ± 6.5% (P = 0.10); phosphorus, 13.0 ± 29.4% vs 16.7 ± 57.2% (P = 0.83) in calcitriol and alfacalcidol, respectively). The mean dose of calcitriol and alfacalcidol were 4.1 and 6.9 µg/week, respectively (P < 0.0001). Conclusion: Alfacalcidol can be used to control secondary hyperparathyroidism at doses of 1.5–2.0 times that of calcitriol. The two drugs are equally efficacious and lead to similar changes in calcium and phosphorus.