Renal insufficiency and magnesium deficiency correlate with a decreased formation of biologically active cholecalciferol: a retrospective observational study.

BACKGROUND: Vitamin D is synthesized in the skin or supplied. Cholecalciferol is hydroxylated in the liver to 25(OH) vitamin D [25D]. 25D is further hydroxylated in the kidney to 1,25(OH) vitamin D [1,25D]. Catabolism occurs by further hydroxylation. Magnesium is a cofactor of all involved hydroxylases. AIM: To investigate the association between renal function and serum magnesium levels, and the biologically active hormone 1,25D. METHOD: Anonymised serum values of 25D, 1,25D, magnesium and creatinine measured in an outpatient cohort over 2 years were analysed. RESULTS: Renal function and magnesium level did not influence 25D values (r = - 0.144 and 0.030, respectively). Mean serum 1,25D values decreased from 106.5 ± 44.3 pmol/l in individuals with normal renal function to 51.7 ± 18.9 pmol/l in those with severe renal insufficiency (p < 0.01). A weak positive correlation was observed between 1,25D and eGFR (r = 0.317), and between 1,25D and serum magnesium (r = 0.217). CONCLUSION: Impaired renal function and low magnesium serum levels are slightly associated with low 1,25D concentrations. Measuring 25D, but not 1,25D, may overestimate the patient's vitamin D status. In patients with renal insufficiency adequate magnesium supply should be ensured.

Vitamin D oral intermittent treatment (DO IT) study, a randomized clinical trial with individual loading regimen.

Comparison of several regimens of oral vitamin D including an individually calculated loading regimen with the aim of achieving serum values > 75 nmol/l. Interventional, randomized, 3-arm study in vitamin D-deficient outpatients. Participants were allocated to supplementation of 24,000 IU vitamin D monthly over three months, using either a monthly drinking solution (Vi-De 3) or capsule (D3 VitaCaps), or an individualized loading regimen with the capsules taken weekly. For the loading regimen, the cumulative dose was calculated according to baseline 25-hydroxy-vitamin D (25(OH)D) serum value and body weight. Main inclusion criteria were age ≥ 18 years and 25(OH)D serum concentration < 50 nmol/l. The primary outcome was 25(OH)D serum concentration one week after treatment termination. Secondary endpoints were patient's preferences and adverse events. Full datasets were obtained from 52 patients. Mean 25(OH)D values were statistically significant higher after a loading regimen compared to a monthly administration of 24,000 IU vitamin D (76.4 ± 15.8 vs 61.4 ± 10.8 nmol/l; p < 0.01). All patients treated with the loading regimen reached sufficient 25(OH)D values > 50 nmol/l. Serum 25(OH)D values > 75 nmol/l were observed more frequently in patients taking the loading regimen (47% vs 11% drinking solution vs 12% capsules). Vitamin D-related adverse effects did not occur in any treatment groups. Capsules were preferred by 88.5% of the patients. Compared to treatments with monthly intake of 24,000 IU vitamin D, the intake of an individually calculated weekly loading regimen was able to raise serum concentrations > 50 nmol/l in all cases within a safe range.

Identification of Patients with Cobalamin Deficiency Crucially Depends on the Diagnostic Strategy.

BACKGROUND: Our goal was to determine vitamin B12 (cobalamin) deficiency with different diagnostic strategies, to propose the best possible laboratory strategy, and to synthesize the relevance of biomarkers in the diagnosis of a cobalamin deficiency. METHODS: We performed a secondary data analysis. The testing strategies were (i) vitamin B12 solely, (ii) holotranscobolamin solely, (iii) vitamin B12 and holotranscobolamin, and (iv) reflex testing of holotranscobalamin in samples with vitamin B12 < 300 pmol. A set of 3,044 laboratory samples with vitamin B12 and holotranscobalamin serum values from unselected in- and outpatients from a secondary care hospital. A sample was classified as cobalamin deficient when low values of vitamin B12 < 137 pmol/L or holotranscobalamin ≤ 37 pmol/L were measured. RESULTS: Low cobalamin values were identified in 591 (19.4%) samples either according to low vitamin B12 values (305; 10.0%) or low holotranscobalamin values (436; 14.3%). For 2,404 values with vitamin B12 < 300 pmol/L, the additional measurement of holotranscobalamin (reflex-testing) enabled the detection of an additional 278 (9.1%) deficiencies. When the grey zone was decreased to 138 - 219 pmol/L, the reflex testing of an additional 1,240 samples identified a total of 511 (16.8%) samples as cobalamin deficient. CONCLUSIONS: The identification of cobalamin deficiency or sufficiency highly depends on the diagnostic strategy. A reflex testing with a grey zone for vitamin B12 < 220 pmol/L identifies cobalamin deficiency cost efficiently in 86.5% cases (511 out of 591). Physicians should apply a uniform strategy on how to address the diagnosis of cobalamin deficiency and indication for treatment. In-hospital guidelines, which describe methodology and sensitivity of the locally used assays for vitamin B12 and holotranscobalamin could guide them.

Oral intermittent vitamin D substitution: influence of pharmaceutical form and dosage frequency on medication adherence: a randomized clinical trial.

BACKGROUND: To assess adherence to and preference for vitamin D substitution with different pharmaceutical forms and frequencies of administration. METHODS: A focus group of stakeholders aimed at preparing the design of an interventional, randomized, cross-over study with 2 × 2 groups obtaining monthly or weekly vitamin D products in liquid or solid form for 3 months each. Dosage corresponds to cumulated amount of recommended 800 IU daily (5.600 IU weekly / 24.000 IU monthly). Main inclusion criteria were a vitamin D serum value < 50 nmol/l and age ≥ 18 years. Primary endpoint was adherence, secondary endpoints were preferences and vitamin D serum levels. RESULTS: The focus group reached consensus for preference of a monthly administration of solid forms to adults. Full datasets were obtained from 97 participants. Adherence was significantly higher with monthly (79.5-100.0%) than weekly (66.4-98.1%) administration. Vitamin D levels increased significantly (p < 0.001) in all participants. An optimal value of > 75 nmol/l was achieved by 32% after 3 months and by 50% after 6 months. Preferred formulation was solid form (tablets, capsules) for 71% of participants, and preferred dosage frequency was monthly for 39% of participants. CONCLUSIONS: Monthly oral vitamin D in solid form lead to the highest adherence, and is preferred by the participants. However, only one third of study participants achieved values in the optimal range of > 75 nmol/l cholecalciferol using weekly or monthly administration providing an average daily cholecalciferol dose of 800 IU. TRIAL REGISTRATION: NCT03121593 | SNCTP000002251 . Registered 30. May 2017,. Prospectively registered.

Validation of a Novel Electronic Device for Medication Adherence Monitoring of Ambulatory Patients.

Several methods exist for measuring medication adherence. The Time4MedTM device (Adherence Innovations, Hong Kong) is a small, electronic card to affix on medication packaging that records date and time of intakes when a button is pushed. We aimed to validate the device with an emphasis on polypharmacy. Twenty volunteers used Time4MedTM devices with a virtual thrice daily intake over 14 days. Diary-recorded date and time were compared to electronically-stored events. Functionality, reliability and recovery for different stress conditions were calculated. User's acceptability was assessed with the System Usability Scale (SUS). Eleven elderly outpatients (mean age 80.2 ± 8.1 years) taking >3 medications daily used the device over 4 weeks. Volunteers logged 847 events. Functionality (100%), sensitivity (94.9%), specificity (99.4%) and recovery (100%) were high. Dropping the smart card and storing it in a refrigerator caused either the recording of false events or no recording at all. The mean SUS score was 82.6 (SD 14.8), demonstrating excellent acceptability. Satisfaction was very high for volunteers and patients, except for pushing the button. Time4MedTM devices are highly accurate in recording, retaining and delivering electronic data of multiple medication intake. They are well accepted by elderly patients. They can be recommended in clinical studies and for practitioners who desire to elucidate adherence patterns of ambulatory patients.

Per oral substitution with 300000 IU vitamin D (Cholecalciferol) reduces bone turnover markers in HIV-infected patients.

BACKGROUND: Osteoporosis and bone fractures seem to be higher in HIV-infected Patients compared to the general populations. Moreover, bone turnover markers are increased in patients on antiretroviral therapy and vitamin D deficiency is prevalent in HIV-infected patients. However, the influence of per oral cholecalciferol on bone metabolism in HIV infected patients is not well understood. METHODS: We measured the bone turnover markers in 96 HIV-infected patients: Bone specific alkaline phosphatase (BSAP), Pyridinoline (PYR), Desoxypyridinoline (DPD) and 25-OH vitamin D. If 25-OH vitamin D was below 75 nnol/L (87/96 patients), 300000 IU cholecalciferol was given per os. 25OH-vitamin D and bone turn over markers were determinded 3 month later. 25 OH-vitamin D was corrected for circannual rythm y'=y+17.875*sin2π/365*day+2.06, whereas bone turnover markers were not corrected. The paired students t-Test was used to compare the two periods. No calcium supplementation or biphosphonate therapy was given. RESULTS: Corrected 25OH-vitamin D levels increased significantly after supplementation (42.7 ± 26.61 vs. 52.85 ± 21.8 nmol/L, p < 0.001). After supplementation, bone turnover markers were significantly lower. The values decreased for BSAP from 21.31 ± 14.32 to 17.53 ± 8.17 µg/L (p < 0.001), PYR from 74.57 ± 36.83 to 54.82 ± 21.43 nmol/mmol creatinine (p < 0.001) and DPD from 15.17 ± 8.34 to 12.61 ± 5.02 nmol/mmol creatinine (p = 0.01). CONCLUSIONS: After per oral substitution with cholecalciferol, bone formation as well as bone resorption markers decreased significant. We postulate a protective effect on bone structure with cholecalciferol supplementation.

Markers of bone turnover are elevated in patients with antiretroviral treatment independent of the substance used.

OBJECTIVES: Osteoporosis and bone fractures are correlated to antiretroviral treatment. It is not clear whether some substances comprise greater risks of bone loss than others. METHODS: We measured pyridinoline, deoxypyridinoline crosslinks, and bone-specific alkaline phosphatase in 113 HIV-positive patients. We compared patients with and without antiretroviral treatment. We then compared patients with versus without tenofovir and patients with protease inhibitor versus nonnucleoside reverse transcriptase inhibitor use. RESULTS: Bone-specific alkaline phosphatase, pyridinoline, and deoxypyridinoline crosslinks were significantly higher in patients with antiretroviral treatment compared with patients without antiretroviral treatment: 24.5 versus 13.04 pg/L (P < 0.001), 82.73 versus 51.93 nmol/mmol (P < 0.001), and 16.56 versus 9.94 nmol/mmol (P < 0.001), respectively. In contrast, no difference was found between patients with and without tenofovir: 25.38 versus 20.02 pg/l (P = 0.1); 79.85 versus 83.95 nmol/mmol (P = 0.64), and 19.12 versus 14.00 nmol/mmol (P = 0.14), respectively. Comparison between patients with protease inhibitor versus nonnucleoside reverse transcriptase inhibitor yielded no difference either: 23.07 versus 27.18 pg/L (P = 0.24), 92.96 versus 80.73 nmol/mmol (P = 0.36), and 18.22 versus 16.39 nmol/mmol (P = 0.55). CONCLUSION: Markers for bone turnover are higher in treated compared with untreated patients. No difference concerning tenofovir use or protease inhibitor versus nonnucleoside reverse transcriptase inhibitor use could be found.