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Background: Despite multiple studies suggesting that low 25(OH)D-vitamin levels are associated with worse outcomes in critically ill individuals, attempts to mitigate the outcomes by fixed dose enteral supplementation unguided by baseline or target blood levels have been unsuccessful. Since a single measurement of 25(OH)D may not optimally reflect an individual's vitamin D status, we studied the plasma concentration of different vitamin D metabolites and their recovery during and following resolution of acute critical illness., Methods: A prospective observational study including patients 18 years and older admitted to a mixed medical-surgical ICU in Reykjavik, Iceland, located at a high-northern altitude (64° N). Vitamin D metabolites were measured at three timepoints; On admission (S1), 3-5 days following admission (S2) and after recovery from acute illness (median 178 days) (S3). Concentrations of total 25(OH)D-vitamin, cholecalciferol (D 3 ), total 24,25(OH)D-vitamin, vitamin D binding protein (VDBP) were measured with LC-tandem mass spectrometry (LC-MS/MS) and free 25-(OH)D was measured with enzyme-linked immunosorbent assay., Results: Most individuals were vitamin D deficient when assessed during critical illness, with 25(OH)D-vitamin levels under 30 ng/ml for 37/40 individuals at timepoint S1 and 34/38 at S2. After recovery, 18/30 patients were deficient at S3. Levels of all vitamin D metabolites measured were low during critical illness but rose substantially following resolution of acute illness. No strong correlation was found between markers of acute illness severity or duration and resolution of vitamin D metabolites in the interval between acute illness and recovery., Conclusions: In critically ill patients, levels of multiple vitamin D metabolites are low but substantial recovery occurs following resolution of acute illness. It is unclear whether a single metabolite is sufficient to assess vitamin D status of critically ill patients and guide potential supplementation., (© 2022 Acta Anaesthesiologica Scandinavica Foundation.)

Objective: Variability in 25-hydroxyvitamin D (25(OH)D) change following vitamin D supplementation exists. Vitamin D metabolite measurement might assist in predicting 25(OH)D response and also contribute to defining vitamin D adequacy. This study assessed utility of vitamin D metabolite measurements to predict 25(OH)D response and explored the relationship between parathyroid hormone (PTH) and a "vitamin D composite index" comprised of the sum of serum 25(OH) D, cholecalciferol (vitamin D 3 ) and 24,25 dihydroxyvitamin D (24,25(OH) 2 D)., Methods: Sixty-two postmenopausal women were randomized to daily vitamin D 3 1,800 IU or placebo for 4 months. Blood was drawn at baseline and after 1 and 4 months. Serum 25(OH)D, vitamin D 3 , and 24,25(OH) 2 D were measured by liquid chromatography tandem mass spectroscopy. Free 25(OH)D and PTH were measured by enzyme-linked immunosorbent assay. Repeated measures analysis of variance and regression analyses were performed., Results: Baseline 25(OH)D was positively correlated (P<.05) with vitamin D3, 24,25(OH) 2 D and free 25(OH) D. Daily vitamin D supplementation increased all metabolites (P<.001). Substantial individual variability in 25(OH) D change at 4 months was observed but was unrelated to baseline vitamin D 3 , 25(OH)D or 24,25(OH) 2 D. Only body mass index, body weight, and body fat mass was associated with 25(OH)D change at 4 months. The vitamin D composite score was associated with serum PTH, but this association was similar to that observed with 25(OH) D alone., Conclusion: This study does not support measurement of vitamin D metabolites in a composite index to assist in prediction of 25(OH)D response to supplementation. Overweight individuals have less robust 25(OH) D response to supplementation, but variability precludes prediction of the result following daily supplementation., Abbreviations: BMI = body mass index DXA = dual-energy X-ray absorptiometry LC-MS/MS = liquid chromatography tandem mass spectroscopy 25(OH)D = 25-hydroxyvitamin D 24,25(OH) 2 D = 24,25 dihydroxyvitamin D PTH = parathyroid hormone vitamin D 3 = cholecalciferol.

Fracture liaison services often perform laboratory testing, but these results may be altered by surgery. In 40 hip arthroplasty patients, many laboratory parameters of bone health relevance were reduced by 8-22% on the first post-operative day. Laboratory results obtained in the immediate post-surgery interval do not reliably ascertain baseline status., Introduction: As secondary causes of osteoporosis are common, fracture liaison services often perform laboratory testing in the immediate post-fracture interval. We hypothesized that laboratory results obtained shortly after surgery may not accurately ascertain baseline status. If true, such alterations might confound subsequent fracture prevention efforts., Methods: Patients undergoing elective total hip arthroplasty were studied as a surrogate for hip fracture patients. Blood and urine were obtained 2 weeks before surgery, before anesthetic induction, on post-operative day one, and 6 weeks after surgery. Serum total and free 25-hydroxyvitamin D (25(OH)D), vitamin D-binding protein (DBP), calcium, creatinine, albumin (Alb), alkaline phosphatase (ALP), plasma hemoglobin (Hgb) and urinary DBP/creatinine ratio (UDBP/Cr) were measured., Results: Forty volunteers (28 women; 12 men) with mean age of 65.7 [8.7] years were studied. Laboratory results were stable from 2 weeks before to the day of surgery. On the first day after surgery, total 25(OH)D, DBP, calcium, creatinine, ALP, and Alb declined 8-22% (p < 0.0001); free 25(OH)D and Hgb declined by 8 and 15% (p < 0.01), respectively; and UDBP/Cr increased 32% (p < 0.01). Using a 25(OH)D <30 ng/mL threshold, vitamin D inadequacy prevalence increased from 38% before surgery to 68% the day after (p < 0.001). All laboratory values returned to baseline at 6 weeks after surgery., Conclusions: Laboratory values are reduced immediately following elective total hip arthroplasty. Testing at that time does not accurately ascertain baseline status and may lead to elevated estimates of vitamin D inadequacy, incorrect interventions, and misallocation of healthcare resources.

Background: To test whether the vitamin D status of anesthesia department caregivers practicing at high Northern latitudes is compatible with current recommendations, the 25-hydroxyvitamin D (25(OH)D) levels of caregivers at hospitals in Iceland (64°08' N) and in Wisconsin (43°07' N) were compared at the end of winter., Methods: Anesthesia department faculty and resident physicians, non-physician anesthetists, and critical care nurses completed a questionnaire, and provided blood samples for analysis of 25(OH)D by reverse-phase high performance liquid chromatography., Results: One hundred and six participants in Iceland and 124 participants in Wisconsin were enrolled. No difference in mean serum 25(OH)D levels between Iceland [70.53 nmol/l, standard deviation (SD) 30.87 nmol/l] and Wisconsin (70.0 nmol/l, SD 30.0 nmol/l) was observed. In Iceland and Wisconsin, 25(OH)D levels below 25 nmol/l were observed in 4.7% and 4.0%, below 50 nmol/l in 34.9% and 25.0%, and below 75 nmol/l in 56.6% and 61.3% of caregivers, respectively., Conclusions: 25(OH)D levels below the 50 nmol/l (20 ng/ml) threshold recommended by the Institute of Medicine and the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis, and below the 75 nmol/l (30 ng/ml) threshold recommended by The Endocrine Society, are highly prevalent among anesthesia caregivers working at two Northern hospitals at the end of winter who may otherwise not meet criteria to be tested. Anesthesia and critical care providers may wish to determine their 25(OH)D levels and use effective, safe, and low cost supplementation to target a 25(OH)D level compatible with optimal health., (© 2014 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Vitamin D is obtained from cutaneous production when 7-dehydrocholesterol is converted to vitamin D(3) (cholecalciferol) by ultraviolet B radiation or by oral intake of vitamin D(2) (ergocalciferol) and D(3). An individual's vitamin D status is best evaluated by measuring the circulating 25-hydroxyvitamin D (25(OH)D) concentration. Although controversy surrounds the definition of low vitamin D status, there is increasing agreement that the optimal circulating 25(OH)D level should be approximately 30 to 32 ng/mL or above. Using this definition, it has been estimated that approximately three-quarters of all adults in the United States have low levels. Low vitamin D status classically has skeletal consequences such as osteomalacia/rickets. More recently, associations between low vitamin D status and increased risk for various nonskeletal morbidities have been recognized; whether all of these associations are causally related to low vitamin D status remains to be determined. To achieve optimal vitamin D status, daily intakes of at least 1000 IU or more of vitamin D are required. The risk of toxicity with "high" amounts of vitamin D intake is low. Substantial between-individual variability exists in response to the same administered vitamin D dose. When to monitor 25(OH)D levels has received little attention. Supplementation with vitamin D(3) may be preferable to vitamin D(2)., (Copyright 2010 Elsevier Inc. All rights reserved.)

As clinicians are more widely appreciating the endemic nature of low vitamin D status, measurement of serum 25-hydroxyvitamin D (25(OH)D), the accepted measure of vitamin D status, has increased. Challenges to 25(OH)D measurement include the presence of 2 forms of vitamin D-ergocalciferol and cholecalciferol (vitamin D(2) and vitamin D(3), respectively)- and the hydrophobic nature of vitamin D. The current state of 25(OH)D measurement is reviewed; modest differences between methodologies persist and confound the application of a single cut point (e.g., 30 ng/mL/75 nmol/L) for the diagnosis of low vitamin D status. The absence of standard calibrators contributes to between-laboratory differences in 25(OH)D measurement. Until there is improved assay standardization and subsequent evidence-based consensus, it seems premature to recommend widespread screening 25(OH)D measurement. Selectively obtaining 25(OH)D measurement in individuals at clinical risk for vitamin D deficiency and/or those most likely to promptly experience benefits from supplementation seems appropriate.

Unlabelled: This prospective study finds that ergocalciferol 50,000 IU three times weekly for four weeks effectively and safely corrects vitamin D inadequacy in nursing home residents., Introduction: Low vitamin D status is common among nursing home residents and contributes to bone loss, falls and fractures. The objective of this study was to evaluate the efficacy and safety of short course, high dose, oral vitamin D(2) (ergocalciferol) treatment., Methods: This prospective study included 63 nursing home residents. The 25 with low vitamin D status (serum 25(OH)D < or = 25 ng/ml) received oral ergocalciferol 50,000 IU three times weekly for four weeks; the others received no change to their routine care. Serum total 25(OH)D, 25(OH)D(2), 25(OH)D(3), calcium, parathyroid hormone (PTH), bone turnover markers and neuro-cognitive assessments were obtained at baseline and four weeks., Results: Mean total 25(OH)D concentration increased (p < 0.0001) from 17.3 to 63.8 ng/ml in the treated group and remained unchanged in the comparison group. Serum 25(OH)D(3) remained stable in the comparison group, but declined (p < 0.0001) with D(2) treatment from 15.4 to 9.1 ng/ml. Serum PTH trended down in the treatment group (p = 0.06). No treatment-induced improvement in ambulation, cognition or behavior was observed. No hypercalcemia or other adverse effects were observed with ergocalciferol treatment., Conclusion: Four weeks of oral vitamin D(2) supplementation effectively and safely normalizes serum 25(OH)D in nursing home residents.

Low vitamin D status, which is endemic due to inadequate oral intake combined with sun avoidance, contributes to musculoskeletal and other pathologies. Although controversial, it is increasingly recommended that serum 25-hydroxyvitamin D (25D) concentrations less than 30 ng/mL be considered suboptimal. Clinicians should appreciate that 25(OH)D measurements, like all quantitative laboratory tests, are subject to assay and biologic variability. Additionally, international standardized calibrators do not exist for 25(OH)D measurement. As such, a single 25(OH)D value of "30 ng/mL" may have substantial variability surrounding it, thereby making 25(OH)D levels of approximately 35 to 40 ng/mL a reasonable therapeutic goal to assure vitamin D adequacy. Achieving such levels often requires vitamin D supplementation. Vitamin D3 (cholecalciferol) or D2 (ergocalciferol) may be used; whether vitamin D3 is more potent than vitamin D2 in maintaining 25(OH)D is controversial.

As a result of low dietary intake and sun avoidance, low vitamin D status is endemic in Wisconsin. In a convenience sample of postmenopausal Wisconsin residents, 59% had suboptimal D status. Only recently, the medical community has begun to appreciate that low vitamin D status underlies multiple deleterious health consequences including skeletal fragility, muscle weakness, and a potential multitude of non-skeletal morbidities. At present, a routine recommendation indicates that at least 1000 IU of vitamin D3 (cholecalciferol) daily is indicated, although the true requirement may be greater. This review details vitamin D physiology and the prevalence of low vitamin D status in Wisconsin and elsewhere, and provides approaches to optimizing vitamin D status.

Context: Lack of sun exposure is widely accepted as the primary cause of epidemic low vitamin D status worldwide. However, some individuals with seemingly adequate UV exposure have been reported to have low serum 25-hydroxyvitamin D [25(OH)D] concentration, results that might have been confounded by imprecision of the assays used., Objective: The aim was to document the 25(OH)D status of healthy individuals with habitually high sun exposure., Setting: This study was conducted in a convenience sample of adults in Honolulu, Hawaii (latitude 21 degrees )., Participants: The study population consisted of 93 adults (30 women and 63 men) with a mean (sem) age and body mass index of 24.0 yr (0.7) and 23.6 kg/m(2) (0.4), respectively. Their self-reported sun exposure was 28.9 (1.5) h/wk, yielding a calculated sun exposure index of 11.1 (0.7)., Main Outcome Measures: Serum 25(OH)D concentration was measured using a precise HPLC assay. Low vitamin D status was defined as a circulating 25(OH)D concentration less than 30 ng/ml., Results: Mean serum 25(OH)D concentration was 31.6 ng/ml. Using a cutpoint of 30 ng/ml, 51% of this population had low vitamin D status. The highest 25(OH)D concentration was 62 ng/ml., Conclusions: These data suggest that variable responsiveness to UVB radiation is evident among individuals, causing some to have low vitamin D status despite abundant sun exposure. In addition, because the maximal 25(OH)D concentration produced by natural UV exposure appears to be approximately 60 ng/ml, it seems prudent to use this value as an upper limit when prescribing vitamin D supplementation.

Endemic hypovitaminosis D contributes to osteoporosis development. However, variation in 25-hydroxyvitamin D (25OHD) measurement is reported and confounds the diagnosis of vitamin D insufficiency/deficiency. This report emphasizes the marked variability observed in serum 25OHD measurements between laboratories.Initially, postmenopausal women had serum 25OHD determinations: 42 in laboratory A, 20 in laboratory B. Their mean (sem) serum 25OHD concentrations were 46 (2.1) and 21 (2.3) ng/ml in laboratories A and B, respectively. Furthermore, there was little overlap in serum 25OHD among these clinically similar individuals. Specifically, 17% of those measured in laboratory A but 90% in laboratory B were below an arbitrary threshold value of 32 ng/ml.Subsequently, serum was obtained from 10 healthy adults. Two aliquots from each individual, one of which was spiked with 20 ng/ml 25OHD, were sent to six laboratories. Substantial variability was noted between these six laboratories. The mean serum 25OHD concentration ranged from 17.1-35.6 ng/ml. Similarly, the mean increase produced by spiking with 20 ng/ml ranged from 7.7-18.0 ng/ml.In conclusion, 25OHD assays yield markedly differing results; whether an individual is found to have low or normal vitamin D status is a function of the laboratory used. If the medical community is to make progress in correcting widespread hypovitaminosis D, 25OHD measurement must be standardized.