Derivation of a formula for adjusting the total serum calcium in Nigeria environment

The total calcium concentration, total protein, albumin and globulin were estimated for 302 patients that reported for serum calcium estimation at the clinical biochemistry laboratory of the Olabisi Onabanjo University Teaching Hospital, Sagamu, Nigeria. Based on regression analysis, three formulae werederived for adjusting the total serum calcium concentration. It was observed that the total serum concentration correlated closely with albumin (a = 0.919 70) but poorly correlated with total protein (a =-0.25 960); where a = correlation coefficient. Adjusted calcium = total calcium – (0.91972 x albumin) +3.70429 was obtaine

Hypocalcemia and Vaso‐Occlusive Painful Crises in Pediatric Sickle Cell Anaemia

Background: Low serum calcium (hypocalcemia) occurs in sickle cell anaemic (SCA) children. Concomitant presence of prolonged corrected QT (QTc) interval on electrocardiogram can ascertain hypocalcemia, especially during vaso-occlusive painful crises (VOC). Aim: The aim of the study was to determine the relationship between hypocalcemia and VOC. Methods: It was a prospective cohort study of 38 SCA children aged 4–17 years during VOC and when the same children were in steady state. Information regarding bone pain and clinical examination were obtained, following which electrocardiography was done during both clinical states. Blood was drawn for total calcium and serum albumin estimation. Results: The mean (standard deviation [SD]) of total calcium was significantly lower during VOC (1.90 [0.19] mmol/l) than during follow-up steady state (2.24 [0.22] mmol/l), P < 0.001. The mean rank of QTc interval was significantly higher during VOC (19.93) than in follow-up steady state (14.50), P < 0.001. Total calcium negatively correlated with QTc intervals during VOC (rs[36] = −0.36, P = 0.029) and follow-up steady state (rs[36] = −0.49, P = 0.002), while QTc interval was highly predictive of hypocalcemia (area under the curve [AUC] = 0.82, P < 0.001). Similarly, total calcium was highly predictive of VOC (AUC = 0.89, P < 0.001) at cutoff point of 2.13 mmol/l with 89.5% sensitivity and 81.6% specificity. Hypocalcemia was significantly observed during VOC than follow‐up steady state (89.5% vs. 21.1%, P < 0.001) with odds ratio of 21.28 (95% confidence interval: 0.012–0.189; P < 0.001). Conclusion: Total calcium <2.13 mmol/l is associated with VOC. Regular total calcium tests should be done. SCA children may benefit from routine oral calcium to reduce frequency of VOC

Validation of an adjusted calcium formula using the Roche calcium (NMBATPA) and albumin (BCG) methods at Groote Schuur Hospital

ABSTRACT: Validation of an adjusted calcium formula using the Roche calcium (NMBATPA) and albumin (BCG) methods at Groote Schuur Hospital Introduction: Most laboratories continue to adjust serum total calcium (tCa) concentration for serum albumin as a surrogate marker of calcium status, despite the availability of ionised calcium (iCa) measurement. Current recommendations by the Association for Clinical Biochemistry and Laboratory Medicine (ACB) advocate that laboratories should use formulae specific for their tCa and albumin methods and analytical platforms. The National Health Laboratory Service at Groote Schuur Hospital (GSH) undertook to investigate this recommendation. An adjusted calcium (aCa) formula specific for the Roche serum tCa and albumin methods was derived from 3131 patients. We investigated the validity and clinical utility of this locally derived aCa formula. Methods: The tCa, albumin and iCa were analysed in blood from 162 inpatients and outpatients at GSH. Corrected calcium (cCa) was calculated using the Payne cCa formula, and aCa was calculated with the new aCa formula. Patients were classified as hypo-, normoor hypercalcaemic using iCa, tCa, cCa and aCa measurements. Cohen's kappa statistic, loglinear and logistic regression models and interclass and concordance correlation coefficients were used to assess agreement between tCa, Payne cCa and aCa against iCa (gold standard). Agreement was further assessed according to renal status and albumin concentrations. Results: The aCa demonstrated good correlation with iCa, but its performance was not significantly better than tCa or Payne cCa in correctly classifying calcium status. Furthermore, albumin concentration was demonstrated to predict the performance of the calcium status classification by the aCa and cCa formulae, irrespective of renal status. Conclusion: The laboratory-specific aCa formula did not perform significantly better than tCa and the Payne cCa formula. This implies that aCa does not add value over tCa where iCa measurements are not readily available

Calcium, vitamin D and iron status of elite rugby union players during a competitive season

Sub-optimal calcium, vitamin D and iron intakes are typical in athletes. However, quantification by dietary intake may be erroneous, with biomarkers providing a more accurate assessment. This study aimed to determine the calcium, vitamin D and iron status of 8 junior (i.e., under-18 [U18]; age 15.5 ± 0.5 years; height 180.4 ± 6.7 cm; body mass 81.6 ± 14.3 kg) and 12 senior (i.e., over-18 [O18]; age 19.7 ± 1.8 years; height 184.9 ± 6.9 cm; body mass 97.4 ± 14.4 kg) male rugby union players, and assess their adequacy against reference values. Fasted serum calcium, 25(OH)D and ferritin concentrations were analysed using Enzyme-Linked Immunosorbent Assay during the in-season period (March-April). U18 had very likely greater calcium concentrations than O18 (2.40 ± 0.08 vs. 2.25 ± 0.19 mmol.l-1). Differences between U18 and O18 were unclear for 25(OH)D (20.21 ± 11.57 vs. 29.02 ± 33.69 nmol.l-1) and ferritin (59.33 ± 34.61 vs. 85.25 ± 73.53 µg.l-1). Compared to reference values, all U18 had adequate serum calcium concentrations, whereas 33% and 67% of O18 were deficient and adequate, respectively. All U18 and 83% of O18 had severely deficient, deficient or inadequate vitamin D concentrations. Adequate (8%) and optimal (8%) concentrations of vitamin D were observed in O18. All U18 and 75% of O18 had adequate ferritin concentrations. Potential toxicity (17%) and deficient (8%) ferritin concentrations were observed in O18. Vitamin D intake should be increased and multiple measures obtained throughout the season. More research is required on the variation of micronutrient statu

A randomized placebo-controlled trial of alphacalcidol on the preservation of beta cell function in children with recent onset type 1 diabetes

SummaryBackground & aimsThis participant-blinded parallel-group randomized placebo-controlled study demonstrated that alfacalcidol (vitamin D analogue) preserves beta cell function in newly diagnosed type 1 diabetes (T1DM) in children.MethodsSubjects from outpatient clinic were randomized to intervention and control groups. Inclusion: (1) age 8–15, (2) T1DM, (3) duration <8 weeks, (4) no chronic diseases, (5) stable diet. Exclusion: (1) vitamin D, calcium supplements or fortified foods, (2) hypercalcemia. Intervention group received alfacalcidol 0.25μg twice daily, while control group received placebo. Insulin given physician-titrated to blood glucose. Safety monitored by serum calcium and phosphate. Beta cell function assessed at 0, 3, 6 months using fasting C-peptide (FCP) and daily insulin dosage per body weight (DID). Primary outcome measured using multivariate repeated measures GLM-ANOVA, with FCP and DID as primary measures and age, gender, sunlight exposure, 25-hydroxy vitamin D, and HbA1c as covariates.ResultsOf 61 subjects, 7 dropped out. GLM-ANOVA showed that groups were different (p=0.019, Eta-squared=0.087), with no significant covariates. FCP was higher and DID lower in the intervention group, with males having stronger responses to alfacalcidol (p=0.001). No adverse effects were observed.ConclusionsThe study confirmed that alfacalcidol can safely preserve beta cell function in newly diagnosed T1DM in children, with a stronger effect in males.Clinical Trial Reg. NoIRCT201205159753N

副作用自発報告データベース及び医療情報データベースを用いた、デノスマブによる低カルシウム血症に関する、発症例の検出及び行政施策の影響評価

Tohoku University齋藤嘉朗課

Vitamin D for older adults : Determinants of status, supplementation strategies and its role in muscle function

Vitamin D has been identified as an important factor in healthy aging and is receiving growing attention in clinical research. Vitamin D is a fat-soluble molecule, which is synthesized by hepatic and renal or extra-renal hydroxylation into the active hormone 1,25-dihydroxyvitamin D (1,25(OH)2D). The main function of this metabolite is to regulate calcium and phosphorus homeostasis and to support bone mineralization. In the circulation, the 25-hydroxyvitamin D metabolite (25(OH)D) is most stable and thus, considered the best marker of vitamin D status. A serum 25(OH)D concentration With the research presented in this thesis, we aimed to gain insight in the prevalence and main determinants of a low vitamin D status, to investigate strategies to prevent or reverse vitamin D deficiency, and to study the effect of vitamin D supplementation on muscle strength and physical performance in Dutch older adults. In chapter 2, we examined the prevalence and the main determinants of a low vitamin D status in a large population of community-dwelling older adults (n=2857). Vitamin D deficiency was highly prevalent, with serum 25(OH)D concentrations To explore potential strategies that prevent vitamin D deficiency, we investigated the contribution of dietary vitamin D intake and specific food groups to serum 25(OH)D concentration in chapter 3. Daily vitamin D intake from dietary sources showed a median (25-75th percentile) intake of 4.0 (3.0-5.4) µg/day (n=595) and only 12-20% of older adults reported to take vitamin D supplements. These findings are in sharp contrast with the current nutrient guidelines and show that the vast majority of older adults do not meet the reference intakes for vitamin D. Nevertheless, significant associations were observed between the highest tertile of dietary vitamin D intake and serum 25(OH)D concentration, suggesting that regular intake of foods rich in vitamin D can support the prevention of modest insufficiency. For the majority of older adults, supplementation is required to ensure sufficient serum 25(OH)D concentrations throughout the year. Currently, supplementation with vitamin D3 is the most common strategy. However, alternative treatment regimens exist that require further investigation. In chapter 4, we report on a dose-response trial (n=59) that investigated the efficacy of calcifediol (5, 10 or 15 µg/d) as a supplementation strategy. Compared to vitamin D3, calcifediol is more hydrophilic, does not require hepatic hydroxylation, and binds with higher affinity to its binding proteins. In our study, we observed that calcifediol was safe and well tolerated in the supplemented doses over the entire study period of 6-months. We concluded that a dose of 10 µg/day resulted in sustained serum 25(OH)D concentrations between 75-100 nmol/L. Furthermore, calcifediol had a ~3 times higher potency when compared to vitamin D3, in increasing serum 25(OH)D concentrations. All in all, calcifediol may offer a valuable supplementation regimen to rapidly correct deficiency. Vitamin D presents an important endocrine regulator in the musculoskeletal health of older adults. Besides its role in bone health, low serum 25(OH)D concentrations have been linked to impaired physical performance and increased risk of falling. The active metabolite 1,25-dihydroxyvitamin D is suggested to act upon a wide variety of cells throughout the body, including muscle cells. Although the exact mechanisms by which vitamin D acts on muscle are unclear, several indirect or direct regulatory pathways have been described, including effects of 1,25-dihyroxyvitamin D through intracellular calcium and phosphate homeostasis, or via activation of transcription factors when binding to the vitamin D receptor in muscle cells. In chapter 5 we observed significant associations between low serum 25(OH)D concentrations, physical performance and frailty in community-dwelling older adults (n=494-756). However, randomized trials are needed to define the causality of the observed associations. A previous pilot study indicated plausible beneficial effects of calcifediol over vitamin D3 on performance and strength. As such, we aimed to further explore the potential role of calcifediol or vitamin D3 on muscle function in chapter 6. We performed a placebo-controlled trial in pre-frail and frail, vitamin D deficient older adults, supplementing either 10 µg/d calcifediol or 20 µg/d vitamin D3, compared to placebo over a 6-month period (n=78). Again, calcifediol induced a faster and higher increase in serum 25(OH)D status when compared to vitamin D3. However, we observed no effect of either supplementation regimen on lower extremity strength or physical performance. Current literature suggests positive effects on strength and balance when supplementing with vitamin D, however, results are inconsistent. Meta-analyses of randomized trials indicate that the beneficial effects of vitamin D supplementation might be more pronounced in vulnerable populations with more severe vitamin D deficiencies. All in all, the high prevalence of vitamin D deficiency is alarming. Promoting adequate vitamin D status is important considering the beneficial effects on bone health. In the last decade, research has come a long way in exploring the role of vitamin D in muscle function. However, the evidence base remains uncertain and further research on the optimal vitamin D status for older adults is needed to guide clinical practice. Until then, focus should be placed on prevention and identification of deficiency. </p