Vitamin D in hematological disorders and malignancies

Commonly known for its critical role in calcium homeostasis and bone mineralization, more recently vitamin D has been implicated in hematological cancer pathogenesis and shows promise as an anti‐cancer therapy. Serum levels of 25(OH)D₃, the precursor to the active form of vitamin D, calcitriol, are frequently lower in patients with hematological disease compared to healthy individuals. This often correlates with worse disease outcome. Furthermore, diseased cells typically highly express the vitamin D receptor, which is required for many of the anti‐cancer effects observed in multiple in vivo and in vitro cancer models. In abnormal hematological cells, vitamin D supplementation promotes apoptosis, induces differentiation, inhibits proliferation, sensitizes tumor cells to other anti‐cancer therapies, and reduces the production of pro‐inflammatory cytokines. Although the dosage of vitamin D required to achieve these effects may induce hypercalcemia in humans, analogs and combinatorial treatments have been developed to circumvent this side effect. Vitamin D and its analogs are well tolerated in clinical trials, and thus, further investigation into the use of these agents in the clinic is warranted. Here, we review the current literature in this field.     

骨化三醇不同剂量及给药途径对血液透析合并重度继发性甲状旁腺功能亢进患者疗效

目的 探讨不同剂量及给药途径的骨化三醇对血液透析合并重度继发性甲状旁腺功能亢进的疗效。方法 60例血液透析合并重度继发性甲状旁腺功能亢进患者随机分为对照组（常规剂量口服骨化三醇）,冲击治疗组（大剂量服用骨化三醇）及静脉用药组（透析后静脉给予骨化三醇注射液）,每4周对血清全段甲状旁腺素(i PTH)、钙、磷进行检测,并观察不良反应。结果 服用12周后,对照组甲状旁腺素水平为（697.5±164.3） pg/ml,相较于治疗前（761.4±184.6） pg/ml,变化不明显（P>0.05）,对重度继发性甲状旁腺功能亢进疗效欠佳;冲击治疗组疗效显著［治疗前：（757.6±170.3） pg/ml,治疗后:（417.6±157.8） pg/ml,P＜0.01］,但是部分患者出现高钙血症;而静脉用药组疗效最佳［治疗前：（814.7±197.8） pg/ml,治疗后（227.4±106.4） pg/ml,P＜0.01］,且较少发生高钙血症。结论 目前,对血液透析合并重度继发性甲状旁腺功能亢进患者,骨化三醇注射液疗效显著,且不良反应较小,可以作为优先选择。     

Topical calcitriol – studies on local tolerance and systemic safety

Calcitriol 3 μg g⁻¹ ointment (Silkis ointment®, Galderma Laboratories) is a new treatment for psoriasis. Calcitriol is the biologically active metabolite of vitamin D₃. It induces keratinocyte differentiation, inhibits keratinocyte, T-cell and fibroblast proliferation, and inhibits the production of some inflammatory mediators, all contributors to the pathogenesis of psoriasis. Preclinical studies have shown an effect of topical calcitriol on calcium homeostasis at doses higher than those in clinical use. No adverse local events were observed when calcitriol was applied to animal skin. Phase I clinical studies confirmed that calcitriol 3 μg g⁻¹ ointment is well tolerated in humans. These studies have demonstrated that at the minimal effective concentration of 3 μg g⁻¹, calcitriol ointment has no discernible photosensitizing or phototoxic potential and no skin irritant or allergic potential in healthy volunteers. Its low systemic absorption through human skin is unlikely to significantly affect calcium homeostasis. This paper summarizes the findings of the preclinical and early clinical studies that provided the foundation of the later Phase II and III clinical trials on efficacy and safety with topical calcitriol 3 μg g⁻¹ ointment for the treatment of plaque psoriasis.     

腰痹康颗粒联合骨化三醇治疗脊柱脆性骨折经皮椎体成形术后的疗效分析

目的观察腰痹康颗粒联合骨化三醇治疗脊柱脆性骨折经皮椎体成形术后(percutaneous vertebroplasty,PVP)的临床疗效。方法依据纳入标准筛选90例脊柱脆性骨折患者,随机分为对照组和观察组,每组各45例。观察组术后口服腰痹康颗粒和骨化三醇,对照组常予以骨化三醇口服,对比术前、术后3 d、4周各组VAS评分、下腰痛功能障碍ODI评分、骨代谢指标包括骨钙素(OC)、I型原胶原N端前肽(PINP)和Ⅰ型胶原C端肽β降解产物(β-CTX)。结果术后3 d、术后4周VAS/ODI评分,观察组明显低于对照组,组间比较差异有统计学意义(P<0.05);两组患者治疗后4周血清β-CTX含量明显降低,OC、PINP含量明显升高,且观察组的变化比对照组更显著,二组之间差异有统计学意义(P<0.05)。结论腰痹康颗粒联合骨化三醇对缓解PVP术后残留腰背疼痛疗效显著,能够改善腰椎活动功能和骨代谢相关指标。     

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.