Denosumab-induced severe hypocalcaemia in a patient with vitamin D deficiency

2020 ◽  
Vol 13 (8) ◽  
pp. e234508 ◽  
Author(s):  
Natasha Daga ◽  
Flavian Joseph

Postmenopausal women are at increased risk of osteoporosis. Osteoporotic fractures carry an increased risk of morbidity and mortality. Denosumab is a monoclonal antibody widely used for the treatment of osteoporosis by inhibiting osteoclast-induced bone resorption. Hypocalcaemia is a known side-effect of denosumab treatment. The majority of such cases have been described in patients with underlying metastatic cancer or chronic kidney disease. We present a patient who developed severe hypocalcaemia after administration of denosumab in the context of severe vitamin D deficiency and a normal kidney function. The management was further complicated by hypophosphatemia. Following replacement of vitamin D, the patient’s calcium and phosphate levels stabilised. The patient required intensive care monitoring for replacement of electrolytes. This case report emphasises the importance of screening and ongoing monitoring of risk factors for iatrogenic hypocalcaemia with denosumab treatment.

2019 ◽  
Vol 144 (16) ◽  
pp. 1120-1124
Author(s):  
Florian Schlereth ◽  
Klaus Badenhoop

AbstractAdequate intake of vitamin D and calcium are fundamental for the treatment of osteoporosis. A normal vitamin D status is required for optimal intestinal calcium absorption. However, general calcium and vitamin D supplementation is not sufficient for prevention of osteoporotic fractures in persons older than 50 years. Nevertheless, vitamin D deficiency should be avoided and corrected. In particular, parts of the population with increased risk for vitamin D deficiency (immobilized or older individuals, swarthy, migrants) should be tested. Secondary causes of vitamin D deficiency should be identified and treated.


2021 ◽  
Vol 22 (6) ◽  
pp. 2896
Author(s):  
Armin Zittermann ◽  
Christian Trummer ◽  
Verena Theiler-Schwetz ◽  
Elisabeth Lerchbaum ◽  
Winfried März ◽  
...  

During the last two decades, the potential impact of vitamin D on the risk of cardiovascular disease (CVD) has been rigorously studied. Data regarding the effect of vitamin D on CVD risk are puzzling: observational data indicate an inverse nonlinear association between vitamin D status and CVD events, with the highest CVD risk at severe vitamin D deficiency; however, preclinical data and randomized controlled trials (RCTs) show several beneficial effects of vitamin D on the surrogate parameters of vascular and cardiac function. By contrast, Mendelian randomization studies and large RCTs in the general population and in patients with chronic kidney disease, a high-risk group for CVD events, largely report no significant beneficial effect of vitamin D treatment on CVD events. In patients with rickets and osteomalacia, cardiovascular complications are infrequently reported, except for an increased risk of heart failure. In conclusion, there is no strong evidence for beneficial vitamin D effects on CVD risk, either in the general population or in high-risk groups. Whether some subgroups such as individuals with severe vitamin D deficiency or a combination of low vitamin D status with specific gene variants and/or certain nutrition/lifestyle factors would benefit from vitamin D (metabolite) administration, remains to be studied.


2021 ◽  
Vol 22 (12) ◽  
pp. 6444
Author(s):  
Anna Gabryanczyk ◽  
Sylwia Klimczak ◽  
Izabela Szymczak-Pajor ◽  
Agnieszka Śliwińska

There is mounting evidence that type 2 diabetes mellitus (T2DM) is related with increased risk for the development of cancer. Apart from shared common risk factors typical for both diseases, diabetes driven factors including hyperinsulinemia, insulin resistance, hyperglycemia and low grade chronic inflammation are of great importance. Recently, vitamin D deficiency was reported to be associated with the pathogenesis of numerous diseases, including T2DM and cancer. However, little is known whether vitamin D deficiency may be responsible for elevated cancer risk development in T2DM patients. Therefore, the aim of the current review is to identify the molecular mechanisms by which vitamin D deficiency may contribute to cancer development in T2DM patients. Vitamin D via alleviation of insulin resistance, hyperglycemia, oxidative stress and inflammation reduces diabetes driven cancer risk factors. Moreover, vitamin D strengthens the DNA repair process, and regulates apoptosis and autophagy of cancer cells as well as signaling pathways involved in tumorigenesis i.e., tumor growth factor β (TGFβ), insulin-like growth factor (IGF) and Wnt-β-Cathenin. It should also be underlined that many types of cancer cells present alterations in vitamin D metabolism and action as a result of Vitamin D Receptor (VDR) and CYP27B1 expression dysregulation. Although, numerous studies revealed that adequate vitamin D concentration prevents or delays T2DM and cancer development, little is known how the vitamin affects cancer risk among T2DM patients. There is a pressing need for randomized clinical trials to clarify whether vitamin D deficiency may be a factor responsible for increased risk of cancer in T2DM patients, and whether the use of the vitamin by patients with diabetes and cancer may improve cancer prognosis and metabolic control of diabetes.


Author(s):  
Matthew F Warren ◽  
Kimberly A Livingston

Abstract The risk of vitamin D insufficiency in humans is a global problem that requires improving ways to increase vitamin D intake. Supplements are a primary means for increasing vitamin D intake, but without a clear consensus on what constitutes vitamin D sufficiency, there is toxicity risk with taking supplements. Chickens have been used in many vitamin D-related research studies, especially studies involving vitamin D supplementation. Our state-of-the-art review evaluates vitamin D metabolism and how the different hydroxylated forms are synthesized. We provide an overview with how vitamin D is absorbed, transported, excreted, and what tissues in the body store vitamin D metabolites. We also discuss a number of studies involving vitamin D supplementation with broilers and laying hens. Vitamin D deficiency and toxicity are also described and how they can be caused. The vitamin D receptor (VDR) is important for vitamin D metabolism. However, there is much more that can be understood with VDR in chickens. Potential research aims involving vitamin D and chickens should explore VDR mechanisms which could lead to newer insights with VDR. Utilizing chickens in future research to help with elucidating vitamin D mechanisms has great potential to advance human nutrition. Finding ways to increase vitamin D intake will be necessary because the coronavirus 2019 disease (COVID-19) pandemic is leading to increased risk of vitamin D deficiency in many populations. Chickens can provide a dual purpose with addressing pandemic-caused vitamin D deficiency: 1) vitamin D supplementation gives chickens added value with possibly leading to vitamin D-enriched meat and egg products; and 2) chickens’ use in research provides data for translational research. Expanding vitamin D-related research in chickens to include more nutritional aims in vitamin D status has great implications with developing better strategies to improve human health.


Stroke ◽  
2014 ◽  
Vol 45 (suppl_1) ◽  
Author(s):  
Suzanne E Judd ◽  
Virginia J Howard ◽  
Paul Muntner ◽  
Brett M Kissela ◽  
Bhupesh Panwar ◽  
...  

Objective: Black Americans are at greater risk of both stroke and vitamin D deficiency than white Americans. We have previously shown that both higher dietary vitamin D and sunlight exposure are associated with decreased risk of stroke; however, serum 25(OH) is thought to be a better marker of vitamin D status. Methods: Using a case cohort design, we examined the association of plasma 25(OH)D with incident stroke in the REasons for Geographic and Racial Differences in Stroke (REGARDS) study, a cohort of black and white participants from across the United States enrolled between 2003 and 2007. Medical records were reviewed by physicians and strokes were classified on the basis of symptoms and neuroimaging. Strokes through July 1, 2011 were included. A stratified cohort sample was selected to ensure approximately equal numbers of black and white participants and an equal distribution across ages. We used Cox proportional hazards models weighted back to the original 30,239 participants, excluding those with history of stroke. Serum 25(OH)D was measured by Immunodetection Systems ELISA. Results: Over mean follow-up of 4.4 years, there were 539 ischemic and 71 hemorrhagic strokes. The stroke-free sub-cohort included 939 participants. After adjustment for age, race, sex, education, diabetes, hypertension, smoking, atrial fibrillation, heart disease, physical activity, kidney function, calcium and phosphorous, 25(OH)D level 30 ng/mL. The direction of association was similar for hemorrhagic stroke though not statistically significant (HR=1.59; 95%CI=0.78, 3.24). Vitamin D deficiency was associated with an increased risk of all stroke (HR=1.54; 95%CI=1.05, 2.23). This effect was greater in blacks (HR=2.09; 95%CI=1.09, 3.99) than whites (HR=1.38; 95%CI=0.78, 2.42). Results were not as strong when we modeled 25(OH)D as a continuous variable (HR=0.99 per 1 ng/ml change in 25(OH)D; 95%CI=0.98, 1.01). Discussion: Similar to low vitamin D intake, vitamin D deficiency is a risk factor for incident stroke. These findings support evidence from cardiovascular and cancer epidemiology that treating low 25(OH)D may prevent strokes.


2010 ◽  
Vol 16 (3) ◽  
pp. 277-281 ◽  
Author(s):  
I. L. Nikitina ◽  
T. L. Karonova ◽  
E. N. Grineva

The high prevalence of vitamin D defi ciency worldwide and the associated increased risk for different pathologies require re-evaluation of this problem and its signifi cance. The wide spectrum of the diseases associated with vitamin D defi ciency explains the high scientifi c interest and increasing number of clinical trials in this area, and the involvement of larger populations into studies.


2017 ◽  
Vol 32 (3) ◽  
pp. 505-513 ◽  
Author(s):  
Young-Jae Park ◽  
Sang-Un Kim ◽  
Kyung-Hee Lee ◽  
Jong-Hak Lee ◽  
Eugene Kwon ◽  
...  

2018 ◽  
Vol 40 (4) ◽  
pp. 1109-1151 ◽  
Author(s):  
Roger Bouillon ◽  
Claudio Marcocci ◽  
Geert Carmeliet ◽  
Daniel Bikle ◽  
John H White ◽  
...  

AbstractThe etiology of endemic rickets was discovered a century ago. Vitamin D is the precursor of 25-hydroxyvitamin D and other metabolites, including 1,25(OH)2D, the ligand for the vitamin D receptor (VDR). The effects of the vitamin D endocrine system on bone and its growth plate are primarily indirect and mediated by its effect on intestinal calcium transport and serum calcium and phosphate homeostasis. Rickets and osteomalacia can be prevented by daily supplements of 400 IU of vitamin D. Vitamin D deficiency (serum 25-hydroxyvitamin D <50 nmol/L) accelerates bone turnover, bone loss, and osteoporotic fractures. These risks can be reduced by 800 IU of vitamin D together with an appropriate calcium intake, given to institutionalized or vitamin D–deficient elderly subjects. VDR and vitamin D metabolic enzymes are widely expressed. Numerous genetic, molecular, cellular, and animal studies strongly suggest that vitamin D signaling has many extraskeletal effects. These include regulation of cell proliferation, immune and muscle function, skin differentiation, and reproduction, as well as vascular and metabolic properties. From observational studies in human subjects, poor vitamin D status is associated with nearly all diseases predicted by these extraskeletal actions. Results of randomized controlled trials and Mendelian randomization studies are supportive of vitamin D supplementation in reducing the incidence of some diseases, but, globally, conclusions are mixed. These findings point to a need for continued ongoing and future basic and clinical studies to better define whether vitamin D status can be optimized to improve many aspects of human health. Vitamin D deficiency enhances the risk of osteoporotic fractures and is associated with many diseases. We review what is established and what is plausible regarding the health effects of vitamin D.


2012 ◽  
Vol 167 (4) ◽  
pp. 553-560 ◽  
Author(s):  
Louise Lind Schierbeck ◽  
Lars Rejnmark ◽  
Charlotte Landbo Tofteng ◽  
Lis Stilgren ◽  
Pia Eiken ◽  
...  

ObjectiveTo investigate the relationship between vitamin D status in healthy women and cardiovascular outcome.Design and methodsBetween 1990 and 1993, 2016 healthy, recently postmenopausal women were enrolled in the Danish Osteoporosis Prevention Study. Serum levels of 25-hydroxyvitamin D (25(OH)D, nmol/l) were measured at baseline. Participants were followed for 16 years. The primary end point was a combination of death, heart failure, myocardial infarction (MI) and stroke. Vitamin D deficiency was defined as serum 25(OH)D<50 nmol/l. The primary end point was adjusted for other risk factors of adverse cardiovascular events (age, smoking, blood pressure, hip–waist ratio, education and family history of MI).ResultsAt baseline, mean age was 50 years and BMI 25. Women with vitamin D deficiency (n=788) had more cardiovascular risk factors than vitamin D-replete women (n=1225). Compared with vitamin D-replete women, women with low 25(OH)D levels had significantly higher BMI and triglycerides, lower HDL and hip–waist ratio and less education. More were smokers among the vitamin D deficient (47 vs 38%). A primary end point was experienced by 118 (15%) with vitamin D deficiency and by 125 (10%) of the vitamin D replete. Hazard ratio (HR) was 1.49 (95% confidence interval: 1.16–1.92;P=0.002) in the vitamin D deficient. Adjusted HR was 1.32 (1.02–1.71;P=0.03). In total, 135 women died; of these, 65 (8%) were of the vitamin D deficient and 70 (6%) in the vitamin D-replete group; unadjusted HR was 1.44 (1.02–2.01;P=0.04) for vitamin D deficiency.ConclusionHealthy women with vitamin D deficiency have increased risk of adverse cardiovascular outcome.


Blood ◽  
2011 ◽  
Vol 117 (10) ◽  
pp. 2800-2806 ◽  
Author(s):  
Todd S. Perlstein ◽  
Reena Pande ◽  
Nancy Berliner ◽  
Gary J. Vanasse

AbstractAnemia and vitamin D deficiency are conditions that both result in significant morbidity and increase with age. The potential relationship between them remains poorly understood, particularly in the elderly. We used the Third National Health and Nutrition Examination Survey to examine the association of vitamin D deficiency with anemia subtypes in persons aged ≥ 60 years. Vitamin D deficiency was defined as serum levels < 20 ng/mL, and anemia was defined according to World Health Organization criteria. Vitamin D deficiency was associated with anemia prevalence independent of age, sex, or race/ethnicity (odds ratio, 1.47; 95% confidence interval, 1.06-2.05; P = .02) and varied significantly by anemia subtype (P overall = .003). The prevalence of vitamin D deficiency was 33.3% in the nonanemic population, 56% in anemia of inflammation (AI; P = .008), and 33.0% in unexplained anemia (P = .55). Non-Hispanic blacks had a 7-fold increased risk of AI compared with whites, and this was partially attenuated after adjusting for vitamin D deficiency. These data show that vitamin D deficiency is associated with specific subtypes of anemia in the elderly, especially in those with AI. Vitamin D may suppress inflammatory pathways, and studies to determine whether vitamin D supplementation ameliorates AI are warranted.


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