High-Dose Intramuscular Vitamin D Provides Long-Lasting Moderate Increases in Serum 25-Hydroxvitamin D Levels and Shorter-Term Changes in Plasma Calcium

2017 ◽  
Vol 100 (5) ◽  
pp. 1337-1344 ◽  
Author(s):  
Shelley Gorman ◽  
Mark Zafir ◽  
Ee Mun Lim ◽  
Michael W Clarke ◽  
Gursimran Dhamrait ◽  
...  

Abstract The best management of vitamin D deficiency, defined as a 25-hydroxyvitamin D [(25(OH)D] level <50nM, is unclear. Intramuscular (IM) injection of a large bolus of vitamin D (≥100 000 IU) is used,but its safety is uncertain. In 10 adults given an IM injection of 600 000IU vitamin D3, we measured at baseline and at 1, 2, 3, and 4 weeks postinjection the serum levels of vitamin D3,25(OH)D3, 25(OH)D2, total 25(OH)D, 3-epi-25(OH)D3, and 24,25-dihydroxyvitamin D3 [24,25(OH)2D3] using a standardized LC with tandem MS (MS/MS)assay; serum levels of 25(OH)D using the Abbott ARCHITECT i2000 immunoassay; and markers of bone metabolism. Bone markers and 25(OH)D (immunoassay) were remeasured at 24 weeks. All participants had baseline total 25(OH)D levels >50 nM. Serum 25(OH)D levels increased at 3, 4, and 24 weeks postinjection, peaking at 4 weeks [mean ± SEM of 126 ± 7.9nM (immunoassay) and 100 ± 5.5 nM (LC-MS/MS)]but generally remained <125 nM, the upper limit recommended by the U.S. Institute of Medicine. Serum 24,25(OH)2D3 levels increased at 3 and 4 weeks postinjection. Serum ionized calcium levels were higher than baseline at 1, 3, and 4 weeks postinjection but remained within the clinicallynormal range. Other biochemical parameters, including other vitamin D metabolites, plasma alkaline phosphatase, and parathyroid hormone levels, were unchanged. IM injection of a large bolus of vitamin D effectively increases serum 25(OH)D levels without evidence of metabolic abnormality.

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A270-A270
Author(s):  
You Joung Heo ◽  
Yun Jeong Lee ◽  
Kyunghoon Lee ◽  
Jae Hyun Kim ◽  
Choong Ho Shin ◽  
...  

Abstract Abstract Context: The “free hormone” hypothesis suggests that the free 25-hydroxyvitamin D (25OHDFree) level may usefully indicate bone health. Objective: To determine which vitamin D measure is optimally correlated with clinical and bone parameters in healthy children. Design and Participants: A cross-sectional study including 146 healthy children (71 boys, 9.5±1.9 years) at a tertiary medical center. Main Outcome Measures: We used a multiplex liquid chromatography-tandem mass spectrometry-based assay to simultaneously measure vitamin D metabolites. The 25OHDFree level was directly measured (m-25OHDFree) or calculated using genotype-constant or genotype-specific affinity coefficients of vitamin D-binding proteins (con-25OHDFree or spe-25OHDFree). Bone mineral content (BMC) and density (BMD) were assessed via dual-energy X-ray absorptiometry. Results: The concentrations of total 25OHD (25OHDTotal), the three forms of 25OHDFree, and 24,25-dihydroxyvitamin D3 correlated with parathyroid hormone levels (all p<0.01). Serum 25OHDTotal and m-25OHDFree levels reflected age, puberty, season, body mass index (BMI), daylight hours, and vitamin D intake (all p<0.05). The con-25OHDFree level better reflected puberty and daylight hours than did the spe-25OHDFree level (both p<0.01). The association between the 25OHDTotal level and bone parameters varied according to the BMI (interaction p<0.05). In 109 normal-weight children, the con-25OHDFree level correlated with BMC and BMD (both p<0.05), but the 25OHDTotal and 24,25-dihydroxyvitamin D3 levels were associated with BMC (both p<0.05). No association was found in overweight or obese children. Conclusions: In healthy children, total and free 25OHD levels comparably reflected lifestyle factors. In normal-weight children, the con-25OHDFree level reflected BMC and BMD, whereas the 25OHDTotal level was associated with BMC.


2013 ◽  
Vol 41 (4) ◽  
pp. 704-708 ◽  
Author(s):  
Linda Björkhem-Bergman ◽  
Hanna Nylén ◽  
Anna-Carin Norlin ◽  
Jonatan D. Lindh ◽  
Lena Ekström ◽  
...  

2020 ◽  
Vol 35 (4) ◽  
pp. 616-623 ◽  
Author(s):  
Charles Ginsberg ◽  
Leila R Zelnick ◽  
Geoffrey A Block ◽  
Glenn M Chertow ◽  
Michel Chonchol ◽  
...  

Abstract Background Phosphate binders are commonly used in the treatment of patients with hyperphosphatemia. While phosphate binders are used to lower phosphate, the effects of specific phosphate binder types on vitamin D metabolism are unknown. Methods We performed a secondary analysis of the Phosphate Normalization Trial in which patients with moderate to advanced chronic kidney disease were randomized to receive either placebo, sevelamer carbonate, lanthanum carbonate or calcium acetate for 9 months. We evaluated changes in serum concentrations of vitamin D metabolites including 24,25-dihydroxyvitamin D3 [24,25(OH)2D3], 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], the ratio of 24,25(OH)2D3 to 25-hydroxyvitamin D [the vitamin D metabolite ratio (VMR)] and the ratio of serum 1,25(OH)2D to 25-hydroxyvitamin D. Results Compared with placebo, randomization to the calcium acetate arm was associated with a 0.6 ng/mL (95% CI 0.2, 1) and 13.5 pg/ng (95% CI 5.5, 21.5) increase in 24,25(OH)2D and VMR, respectively, and a 5.2 pg/mL (95% CI 1.1, 9.4) reduction in 1,25(OH)2D. Randomization to sevelamer carbonate was associated with a 0.5 ng/mL (95% CI −0.9, −0.1) and 11.8 pg/ng (95% CI −20, −3.5) reduction in 24,25(OH)2D3 and VMR, respectively. There was no association of the sevelamer arm with the change in 1,25(OH)2D3, and randomization to lanthanum carbonate was not associated with a change in any of the vitamin D metabolites. Conclusion Administration of different phosphate binders to patients with moderate to severe CKD results in unique changes in vitamin D metabolism.


1984 ◽  
Vol 52 (2) ◽  
pp. 329-334 ◽  
Author(s):  
Saleh H. Sedrani

1. The effects of vitamin D3(D3) on serum levels of 1, 25-dihydroxyvitamin D3(1, 25(OH)2D3), ionic calcium, total Ca and phosphorus in chicks were studied from the time of hatching until sexual maturity.2. Chicks fed on a diet low in D3showed a serum level of 1, 25(OH)2D3higher than that in chicks on a normal-D3diet, for both sexes and at any given age.3. A dramatic increase in the serum level of 1, 25(OH)2D3occurred in female birds approaching sexual maturity and in laying hens raised on the low-D3diet the level was five times that of their counterparts raised on a normal-D3diet.4. Theserum 1, 25(OH)2D3levelin adultmalesin thelow-D3groups wasseven timesthatofthoseon thenormal-D3diet.5. The serum level of 25-hydroxyvitamin D3remained relatively unchanged at weeks 2 and 15 in birds on a low D3intake as well as in those fed on a normal-D3diet. Nevertheless, the levels of 25-hydroxyvitamin D3were different between the two groups.6. No significant change was observed in the level of ionized serum Ca in relation to dietary regimen, but there was an increase in total Ca concentration in females with the onset of reproduction.7. The serum P level decreased gradually with age, reaching a minimum value 3 and 8 weeks before laying commenced in the groups on low- and normal-D3diets respectively. An increase was observed when the hens began laying.8. Chicks adapted to a low-D3diet by elevation of their plasma level of 1, 25(OH)2D3. The mechanism by which this is achieved is not known, but the results suggest that parathyroid hormone, Ca and P are unlikely to play roles in the adaptive increase in the level of 1, 25(OH)2D3in the blood of chicks given a minimal amount of D3. The possibility that the rate of degradation of 1, 25(OH)2D3is greatly reduced under these conditions cannot be excluded and this could account for the level of this metabolite in those birds.


1998 ◽  
Vol 83 (11) ◽  
pp. 3832-3838 ◽  
Author(s):  
Charlotte J. Haug ◽  
Pål Aukrust ◽  
Egil Haug ◽  
Lars Mørkrid ◽  
Fredrik Müller ◽  
...  

The serum level of 1,25-dihydroxyvitamin D3[ 1,25-(OH)2D], the biologically most potent metabolite of vitamin D, is tightly regulated within narrow limits in human healthy adults. 1,25-(OH)2D deficiency is rare and is associated with disturbances in calcium and bone metabolism. We have previously reported a marked decrease in serum levels of 1,25-(OH)2D in human immunodeficiency virus (HIV)-infected patients. The present study was designed to further examine the causes and consequences of severe 1,25-(OH)2D deficiency in these patients. The design was a prospective cohort study. Fifty-four HIV-infected patients clinically classified according to the revised criteria from Centers for Disease Control and Prevention and healthy controls were studied. Parameters related to vitamin D and calcium metabolism as well as immunological and nutritional status were determined. Twenty-nine of the patients (54%) had serum levels of 1,25-(OH)2D below the lower reference limit, and 18 of these had undetectable levels. In contrast, HIV-infected patients had normal serum levels of 25-hydroxyvitamin D and vitamin D-binding protein. HIV-infected patients as a group had modestly depressed serum calcium and PTH levels. There were, however, no correlations between these parameters and serum levels of 1,25-(OH)2D. There were no differences in serum calcium or PTH levels or nutritional status when patients with severe 1,25-(OH)2D deficiency were compared to other patients, but patients with undetectable 1,25-(OH)2D had significantly elevated serum phosphate levels. Furthermore, patients with undetectable 1,25-(OH)2D levels were characterized by advanced clinical HIV infection, low CD4+ lymphocyte counts, and high serum levels of tumor necrosis factor-α (TNFα). We conclude that inadequate 1α-hydroxylation of 25-hydroxyvitamin D seems to be the most likely cause of 1,25-(OH)2D deficiency in HIV-infected patients, possibly induced by an inhibitory effect of TNFα. The low 1,25-(OH)2D and high TNFα levels observed may impair the immune response in HIV-infected patients both independently and in combination and may represent an important feature of the pathogenesis of HIV-related immunodeficiency. Markedly depressed 1,25-(OH)2D serum levels are also present in certain other disorders characterized by immunological hyperactivity. Thus, the findings in the present study may not only represent a previously unrecognized immune-mediated mechanism for induction of 1,25-(OH)2D deficiency in human disease, but may also reflect the importance of adequate serum levels of 1,25-(OH)2D for satisfactory performance of the immune system in man.


2016 ◽  
Vol 37 (5) ◽  
pp. 521-547 ◽  
Author(s):  
Peter J. Tebben ◽  
Ravinder J. Singh ◽  
Rajiv Kumar

AbstractHypercalcemia occurs in up to 4% of the population in association with malignancy, primary hyperparathyroidism, ingestion of excessive calcium and/or vitamin D, ectopic production of 1,25-dihydroxyvitamin D [1,25(OH)2D], and impaired degradation of 1,25(OH)2D. The ingestion of excessive amounts of vitamin D3 (or vitamin D2) results in hypercalcemia and hypercalciuria due to the formation of supraphysiological amounts of 25-hydroxyvitamin D [25(OH)D] that bind to the vitamin D receptor, albeit with lower affinity than the active form of the vitamin, 1,25(OH)2D, and the formation of 5,6-trans 25(OH)D, which binds to the vitamin D receptor more tightly than 25(OH)D. In patients with granulomatous disease such as sarcoidosis or tuberculosis and tumors such as lymphomas, hypercalcemia occurs as a result of the activity of ectopic 25(OH)D-1-hydroxylase (CYP27B1) expressed in macrophages or tumor cells and the formation of excessive amounts of 1,25(OH)2D. Recent work has identified a novel cause of non-PTH-mediated hypercalcemia that occurs when the degradation of 1,25(OH)2D is impaired as a result of mutations of the 1,25(OH)2D-24-hydroxylase cytochrome P450 (CYP24A1). Patients with biallelic and, in some instances, monoallelic mutations of the CYP24A1 gene have elevated serum calcium concentrations associated with elevated serum 1,25(OH)2D, suppressed PTH concentrations, hypercalciuria, nephrocalcinosis, nephrolithiasis, and on occasion, reduced bone density. Of interest, first-time calcium renal stone formers have elevated 1,25(OH)2D and evidence of impaired 24-hydroxylase-mediated 1,25(OH)2D degradation. We will describe the biochemical processes associated with the synthesis and degradation of various vitamin D metabolites, the clinical features of the vitamin D-mediated hypercalcemia, their biochemical diagnosis, and treatment.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1699.1-1700
Author(s):  
F. Masini ◽  
K. Gjeloshi ◽  
E. Pinotti ◽  
F. Danzo ◽  
F. Guarino ◽  
...  

Background:The association between hyperuricemia and psoriatic arthritis (PsA) is actually generally accepted. Previous studies have demonstrated that uric acid suppress 25(OH)D metabolism [1]. More evidence is required to demonstrate the immune modulatory effects in psoriasis, psoriatic arthritis and other autoimmune diseases. In particular, the potential association between 25-hydroxyvitamin D serum levels and PsA still remains unknown.Objectives:To assess a clinical association between uric acid/25(OH)D serum levels ratio related to PASI, BASDAI and DAPSA, if any, in patients with psoriatic arthritis.Methods:We retrospectively observed 61 patients with psoriatic arthritis referred to our outpatients clinic, independently from already being on therapy or naïve. All selected patients underwent only conventional non-biological therapy at baseline and none received vitamin D supplementation and either allopurinol or febuxostat previously. Blood samples were drawn from all participants for assessment of 25-hydroxyvitamin D and uric acid serum levels. Disease activity of psoriasis and psoriatic arthritis were assessed by the Psoriasis Area and Severity Index (PASI), the Disease Activity Index for Psoriatic Arthritis (DAPSA) and the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). We assessed the covariates of interest by the Wilcoxon non parametric test, through the SPSS 24 Software.Results:We observed 61 patients, mainly females (83.6%). At the univariate analysis, the uric acid/25(OH)D serum levels ratio revealed significantly associated with DAPSA and BASDAI indexes (p<0.001 and p<0.001, respectively), whilst no significant association emerged with the PASI index (p=0.462).Conclusion:Data in the literature about these associations in the context of psoriatic arthritis are really poor. As a consequence, our findings, though preliminary, suggest us to hypothesize a potential role of uric acid/25(OH)D serum levels ratio as potential inflammation marker in order to better assess the disease activity. However, future larger studies are needed to investigate more in depth this association.[1]Charoenngam N, Ponvilawan B, Ungprasert P. Vitamin D insufficiency and deficiency are associated with a higher level of serum uric acid: A systematic review and meta-analysis. Mod Rheumatol. 2019 Mar 4:1-6.Disclosure of Interests:None declared


2015 ◽  
Vol 18 (02) ◽  
pp. 1550008 ◽  
Author(s):  
Negin Masoudi Alavi ◽  
Mahla Madani ◽  
Mohsen Taghizadeh ◽  
Mohammad Reza Sharif

Purpose: To investigate the effect of weekly single high dose vitamin D supplementation on serum 25-hydroxyvitamin D [25(OH)D], and non-specific musculoskeletal pain in female nurses. Methods: In this prospective study in Kashan/Iran, from April 1, 2014, through September 30, 2014, the 150 nurses with vitamin D deficiency received the weekly pearls of 50,000 units of vitamin D3 for 10 weeks. The serum level of 25(OH)D was measured before and after supplement therapy. The subjects were also asked to complete the Extended Nordic Musculoskeletal Questionnaire. All analyses were conducted with SPSS version 16. Results: After 10 weeks of intervention there was [Formula: see text][Formula: see text]ng/mL increase in 25(OH)D. The 82 nurses (54.7%) had 25(OH)D in normal range, while the 68 nurses (45.3%) were still vitamin D deficient. Weight could explain 15.4% increase in 25(OH)D. Before intervention 135 (90%), of nurses reported musculoskeletal pain in at least one region, after intervention this number decreased to 72.7%. There was a statistically significant improvement in musculoskeletal pain in neck, shoulders, upper back, lower back, hips/tights, knees, and ankles/feet after intervention. Conclusions: The weekly single high dose of vitamin D for 10 weeks could resolve vitamin D deficiency in about half of the patients. Patients with non-specific musculoskeletal pain might benefit from vitamin D supplementation.


2013 ◽  
Vol 98 (12) ◽  
pp. 4619-4628 ◽  
Author(s):  
Bruce W. Hollis ◽  
Carol L. Wagner

Context: There is no doubt that vitamin D must be activated to the hormonal form 1,25-dihydroxyvitamin D to achieve full biological activity or that many tissues participate in this activation process—be it endocrine or autocrine. We believe that not only is 25-hydroxyvitamin D important to tissue delivery for this activation process, but also that intact vitamin D has a pivotal role in this process. Objective: In this review, evidence on the vitamin D endocrine/autocrine system is presented and discussed in relation to vitamin D-binding protein affinity, circulating half-lives, and enzymatic transformations of vitamin D metabolites, and how these affect biological action in any given tissue. Conclusions: Circulating vitamin D, the parent compound, likely plays an important physiological role with respect to the vitamin D endocrine/autocrine system, as a substrate in many tissues, not originally thought to be important. Based on emerging data from the laboratory, clinical trials, and data on circulating 25-hydroxyvitamin D amassed during many decades, it is likely that for the optimal functioning of these systems, significant vitamin D should be available on a daily basis to ensure stable circulating concentrations, implying that variation in vitamin D dosing schedules could have profound effects on the outcomes of clinical trials because of the short circulating half-life of intact vitamin D.


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