- Hypercalcaemia-induced kidney injury caused by the vitamin D analogue calcitriol for psoriasis: a note of caution when prescribing topical treatment. [Journal Article]
- CEClin Exp Dermatol 2016 Oct 20
- A 55-year-old man with severe plaque psoriasis presented with a 2-week history of feeling generally unwell with lethargy and thirst. His symptoms had developed 6 weeks after commencement of the topic...
A 55-year-old man with severe plaque psoriasis presented with a 2-week history of feeling generally unwell with lethargy and thirst. His symptoms had developed 6 weeks after commencement of the topical vitamin D3 analogue calcitriol. Investigations revealed hypercalcaemia and acute-on-chronic kidney injury, probably directly induced by systemic absorption of vitamin D3 following extensive topical use. Topical calcitriol had been started as a steroid-sparing agent to reduce the patient's liberal potent corticosteroid usage during anti-tumour necrosis factor-alfa therapy. Topical vitamin D analogues are commonly prescribed in dermatological and general practice, with hypercalcaemia being a rare but potentially serious adverse effect. This case serves to outline key factors that may predispose to hypercalcaemia, such as disease extent, quantity of drug applied, comorbidities and concurrent medications, and it highlights the importance of considering these factors when prescribing topical therapies.
- Sclerostin and Bone Aging: A Mini-Review. [Journal Article]
- GGerontology 2016 May 14
- Sclerostin, mainly produced by osteocytes, is now considered a major regulator of bone formation. Identified from patients with a low bone mass, sclerostin inhibits the Wnt pathway by binding to LRP5...
Sclerostin, mainly produced by osteocytes, is now considered a major regulator of bone formation. Identified from patients with a low bone mass, sclerostin inhibits the Wnt pathway by binding to LRP5/6 and subsequently increases bone formation. Sclerostin may also play a role in the mediation of systemic and local factors such as calcitriol, PTH, glucocorticoids and tumor necrosis factor-alpha. Circulating sclerostin levels increase with age and with the decline of kidney function. However, they are surprisingly higher in patients with a high bone mineral density, suggesting that sclerostin may be a relevant marker of the pool of mature osteocytes. The anti-anabolic properties lead to the development of anti-sclerostin biotherapies that are under current evaluation. The results of these clinical trials will open new promising opportunities for the treatment of osteoporosis and bone fragility fractures.
- Vascular Calcification Induced by Chronic Kidney Disease Is Mediated by an Increase of 1α-Hydroxylase Expression in Vascular Smooth Muscle Cells. [Journal Article]
- JBJ Bone Miner Res 2016; 31(10):1865-1876
- Vascular calcification (VC) is a complication of chronic kidney disease that predicts morbidity and mortality. Uremic serum promotes VC, but the mechanism involved is unknown. A role for 1,25(OH)2 D3...
Vascular calcification (VC) is a complication of chronic kidney disease that predicts morbidity and mortality. Uremic serum promotes VC, but the mechanism involved is unknown. A role for 1,25(OH)2 D3 in VC has been proposed, but the mechanism is unclear because both low and high levels have been shown to increase it. In this work we investigate the role of 1,25(OH)2 D3 produced in vascular smooth muscle cells (VSMCs) in VC. Rats with subtotal nephrectomy and kidney recipient patients showed increased arterial expression of 1α-hydroxylase in vivo. VSMCs exposed in vitro to serum obtained from uremic rats also showed increased 1α-hydroxylase expression. Those increases were parallel to an increase in VC. After 6 days with high phosphate media, VSMCs overexpressing 1α-hydroxylase show significantly higher calcium content and RUNX2 expression than control cells. 1α-hydroxylase null mice (KO) with subtotal nephrectomy and treated with calcitriol (400 ng/kg) for 2 weeks showed significantly lower levels of vascular calcium content, Alizarin red staining, and RUNX2 expression than wild-type (WT) littermates. Serum calcium, phosphorus, blood urea nitrogen (BUN), PTH, and 1,25(OH)2 D3 levels were similar in both calcitriol-treated groups. In vitro, WT VSMCs treated with uremic serum also showed a significant increase in 1α-hydroxylase expression and higher calcification that was not observed in KO cells. We conclude that local activation of 1α-hydroxylase in the artery mediates VC observed in uremia. © 2016 American Society for Bone and Mineral Research.
- Vitamin D in haematological disorders and malignancies. [Review]
- EJEur J Haematol 2016 Oct 15
- Commonly known for its critical role in calcium homeostasis and bone mineralization, more recently vitamin D has been implicated in haematological cancer pathogenesis and shows promise as an anti-can...
Commonly known for its critical role in calcium homeostasis and bone mineralization, more recently vitamin D has been implicated in haematological 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 typically lower in patients with haematological disease compared to healthy individuals. This often correlates with worse disease outcome. Furthermore, diseased cells typically highly express the vitamin D receptor (VDR), which is required for many of the anti-cancer effects observed in multiple in vivo and in vitro cancer models. In abnormal haematological 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. This article is protected by copyright. All rights reserved.
- ANNALS EXPRESS: Vitamin D binding protein as it is understood in 2016: is it a critical key with which to help to solve the calcitriol conundrum? [Journal Article]
- ACAnn Clin Biochem 2016 Oct 13
- CONCLUSIONS: This review reports our current understanding of DBP. Its genetic determinants and their effect on it and secondarily on calcifediol concentrations and assays are described. Its complex interplay with parathyroid hormone is considered.The analytical state of the art is translated into the challenge it imposes clinically, in the formulation of reference intervals and in their use in advising and managing patients. Several recent challenges thrown up to laboratories by percipient clinicians highlight the dilemma DBP poses. A way forward is suggested.
- A case report of mediastinal ectopic parathyroid adenoma presented as parathyroid crisis localized by SPECT/CT. [Journal Article]
- MMedicine (Baltimore) 2016; 95(41):e5157
- CONCLUSIONS: Any parathyroid crisis without parathyroid adenoma in the neck should alert physicians to search for ectopic locations through combination of imaging techniques.
- Cost-effectiveness analysis of paricalcitol versus calcitriol for the treatment of SHPT in dialytic patients from the SUS perspective. [Journal Article]
- JBJ Bras Nefrol 2016 Jul-Sep; 38(3):313-319
- CONCLUSIONS: According to cost-effectiveness threshold recommended by the World Health Organization for 2013, the treatment of SHPT in patients on dialysis with paricalcitol is cost-effective when compared to calcitriol, from the public healthcare system perspective, in Brazil.
- Treatment of ear and bone disease in the Phex mouse mutant with dietary supplementation. [Journal Article]
- AJAm J Otolaryngol 2016 Sep 28
- CONCLUSIONS: Supplementation with phosphorus and calcitriol improves otic capsule bone morphology in the Phex male mouse but does not alter development of ELH or SNHL.
- Effect of daily calcitriol supplementation with and without calcium on disease regression in non-alcoholic fatty liver patients following an energy-restricted diet: Randomized, controlled, double-blind trial. [Journal Article]
- CNClin Nutr 2016 Sep 28
- CONCLUSIONS: Our results suggest that calcium plus calcitriol supplementation for 12 weeks may be potentially effective for biochemical parameters in NAFLD patients. Further additional larger controlled trials are needed to confirm these findings.
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- Vitamin D decreases STAT phosphorylation and inflammatory cytokine output in T-LGL Leukemia. [Journal Article]
- CBCancer Biol Ther 2016 Oct 7; :0
- Large granular lymphocyte leukemia (LGLL) is a rare incurable chronic disease typically characterized by clonal expansion of CD3+ cytotoxic T-cells. Two signal transducer and activator of transcripti...
Large granular lymphocyte leukemia (LGLL) is a rare incurable chronic disease typically characterized by clonal expansion of CD3+ cytotoxic T-cells. Two signal transducer and activator of transcription factors, STAT1 and STAT3, are constitutively active in T-LGLL. Disruption of this activation induces apoptosis in T-LGLL cells. Therefore, considerable efforts are focused on developing treatments that inhibit STAT activation. Calcitriol, the active form of vitamin D, has been shown to decrease STAT1 and STAT3 phosphorylation in cancer cell lines and autoimmune disease mouse models. Thus, we investigated whether calcitriol could be a valid therapeutic for T-LGLL. Calcitriol treatment of the TL-1 cell line (model of T-LGLL) led to decreased phospho-Y701 STAT1 and phospho-Y705 STAT3 and increased vitamin D receptor (VDR) levels. Doses of 10 and 100 nM calcitriol also significantly decreased the inflammatory cytokine IFN-γ in the TL-1 cell line. The overall cell viability did not change when the TL-1 cell line was treated with 0.1 to 1000 nM calcitriol. Studies with primary T-LGLL patient peripheral blood mononuclear cells showed that the majority of T-LGLL patients have detectable VDR and activated STATs in contrast to normal donor controls. Treatment of primary T-LGLL patient cells with calcitriol recapitulated findings from the TL-1 cell line. Overall, our results suggest that calcitriol may reprogram T-cells to decrease essential STAT activation and pro-inflammatory cytokine output. These data support further investigation into calcitriol as an experimental therapeutic for T-LGLL.