Assessment criteria for vitamin D deficiency/insufficiency in Japan - proposal by an expert panel supported by Research Program of Intractable Diseases, Ministry of Health, Labour and Welfare, Japan, The Japanese Society for Bone and Mineral Research and The Japan Endocrine Society [Opinion].

Vitamin D is indispensable for the maintenance of bone and mineral health. Inadequate vitamin D action increases the risk for various musculoskeletal/mineral events including fracture, fall, secondary hyperparathyroidism, diminished response to antiresorptives, rickets/osteomalacia, and hypocalcemia. Its most common cause in recent years is vitamin D deficiency/insufficiency, clinically defined by low serum 25-hydroxyvitamin D [25(OH)D] level. Guidelines for vitamin D insufficiency/deficiency defined by serum 25(OH)D concentrations have been published all over the world. In Japan, however, the information on the associations between serum 25(OH)D and bone and mineral disorders has not been widely shared among healthcare providers, partly because its measurement had not been reimbursed with national medical insurance policy until August 2016. We have set out to collect and analyze Japanese data on the relationship between serum 25(OH)D concentration and bone and mineral events. Integrating these domestic data and published guidelines worldwide, here we present the following assessment criteria for vitamin D sufficiency/insufficiency/deficiency using serum 25(OH)D level in Japan. 1) Serum 25(OH)D level equal to or above 30 ng/mL is considered to be vitamin D sufficient. 2) Serum 25(OH)D level less than 30 ng/mL but not less than 20 ng/mL is considered to be vitamin D insufficient. 3) Serum 25(OH)D level less than 20 ng/mL is considered to be vitamin D deficient. We believe that these criteria will be clinically helpful in the assessment of serum 25(OH)D concentrations and further expect that they will form a basis for the future development of guidelines for the management of vitamin D deficiency/insufficiency.

Less than adequate vitamin D status and intake in Latin America and the Caribbean:a problem of unknown magnitude.

BACKGROUND: The prevalence of vitamin D deficiency in Latin America and the Caribbean is unknown. OBJECTIVE: To examine the prevalence data available on vitamin D deficiency in Latin America and the Caribbean. METHODS: A systematic review was conducted in 2011. Studies using biochemical biomarkers and dietary intake estimation were included. Studies conducted in apparently healthy individuals, independently of age, latitude, skin pigmentation, and season of the year at the time of blood collection, were included. RESULTS: A total of 243 studies were identified. The final number of selected studies was 28, including two National Health Surveys (Mexico and Argentina). There are studies that report the vitamin D status of specific subgroups conducted in Argentina, Brazil, Chile, Colombia, Ecuador, Guatemala, and Mexico. However, the small sample sizes in these studies and thus the low national representativeness of the reported data do not allow for an accurate assessment of vitamin D status at the regional level. In the majority of the countries with available data, we observed that vitamin D insufficiency was classified as a mild, moderate, or severe public health problem. The only country with a nationally representative sample was Mexico, which found 24%, 10%, 8%, and 10% prevalence rates of vitamin D insufficiency (25-hydroxyvitamin D < 50 nmol/L) in preschoolers, schoolchildren, adolescents, and adults, respectively. The prevalence of vitamin D deficiency (25-hydroxyvitamin D < 20 nmol/L) was less than 1% for all groups. CONCLUSIONS: There is some indication that vitamin D insufficiency may be a public health problem in Latin America and the Caribbean, but the exact magnitude is currently unknown.

The discriminative value of various biochemical parameters in detecting varying degrees of vitamin D deficiency in the Iranian population.

BACKGROUND: The present study was designed to assess the status and the discriminatory ability of serum Alk-Ph, Ca, P, and PTH in detecting hypovitaminosis D in some selected Iranian populations. METHODS: Using a random cluster sample of apparently healthy men and women, this multi-centric cross-sectional study was carried out among the Iranian urban population of five large cities (Tehran, Tabriz, Mashhad, Shiraz, and Booshehr). Serum levels of 25(OH)D, PTH, Alk-Ph, Ca, and P levels were analyzed. Analysis of variance (ANOVA) was used to estimate the main effects by comparing the mean values of serum PTH, Alk-Ph, Ca, and P at different 25(OH)D levels. The discriminative value of the studied biochemical markers in detecting hypovitaminosis D was assessed by ROC curve analysis. RESULTS: From among the studied subjects, 2164 (57.5%) had moderate to severe vitamin D deficiency. The areas under the ROC curves showed the low accuracy of PTH (0.579), Alk-Ph (0.478), Ca (0.496), and P (0.406) in detecting subjects with a vitamin D concentration < 20 ng/mL. CONCLUSIONS: Abnormalities in routine markers of bone profile such as PTH, Alk-Ph, Ca, and P are not adequate enough to discriminate patients with hypovitaminosis D.

High prevalence of vitamin D insufficiency in healthy elderly people living at home in Argentina.

OBJECTIVE: To evaluate the nutritional status of vitamin D in urban populations of healthy elderly people living at home, in different regions of Argentina. DESIGN: Cross-sectional study. SUBJECTS: In total, 386 ambulatory subjects over 65 y of age from seven cities (between latitude 26 degrees S and 55 degrees S) were asked to participate between the end of winter and the beginning of spring. Of these, 369 accepted, 30 were excluded because of medical history or abnormal biochemical determinations. Finally, 339 subjects (226 women and 113 men) (X+/-s.d.) (71.3+/- 5.2 y) were included. RESULTS: Serum 25OHD levels were lowest in the South (latitude range: 41 degrees S-55 degrees S): 14.2+/-5.6 ng/ml (P<0.0001vs North and Mid regions); highest in the North (26 degrees S-27 degrees S): 20.7+/-7.4 ng/ml (P<0.03 vs Mid, P<0.0001vs South); and intermediate in the Mid region (33 degrees S-34 degrees S) 17.9+/-8.2 ng/ml. Serum mid-molecule PTH (mmPTH) and 25OHD were inversely related: (r=-0.24, P<0.001). A cutoff level of 25OHD at which serum mmPTH levels began to increase was established at 27 ng/ml. A high prevalence (87-52%) of subjects with 25OHD levels in the deficiency-insufficiency range (25OHD levels <20 ng/ml) was detected. CONCLUSION: This study shows that vitamin D deficiency/insufficiency in the elderly is a worldwide problem. Correction of this deficit would have a positive impact on bone health of elderly people.

Hypothesis: the case for quaternary hyperparathyroidism.

We report the case of a young woman with hyperparathyroidism due to a large parathyroid adenoma associated with severe vitamin D deficiency. The case is noteworthy for the size of the parathyroid adenoma and for the young age at presentation, and is more typical of the presentation of hyperparathyroidism seen in developing countries where the prevalence of vitamin D deficiency is high. Vitamin D is known to have a suppressive effect on parathyroid cell proliferation and parathyroid hormone synthesis. Vitamin D deficiency may result in a compensatory increase in the secretion of parathyroid hormone (secondary hyperparathyroidism) which involves hyperplasia of all four parathyroid glands. Secondary hyperparathyroidism can become autonomous and this has been termed tertiary hyperparathyroidism, the underlying pathology of which has been variably described in the literature as adenoma formation or four gland hyperplasia. The pathogenesis of parathyroid adenoma formation in vitamin D deficiency remains unclear. It is possible that a proportion of cases represent the coincidence of primary hyperparathyroidism in patients with vitamin D deficiency. Alternatively, we hypothesise that autonomous four gland hyperplasia or tertiary hyperparathyroidism may progress to adenoma formation and that this should be termed 'quaternary hyperparathyroidism'.

Plasma 1,25(OH)2D levels decrease in postmenopausal women with hypovitaminosis D.

OBJECTIVE: Although calcitriol (1,25(OH)2D) is considered the biologically active vitamin D metabolite, several studies have shown that calcidiol (25OHD) is the vitamin D metabolite that is most closely linked to parathyroid function and indices of calcium homeostasis. Moreover, low levels of 25OHD have been associated with increased risk of different diseases including cancer, diabetes, and myopathy. DESIGN: Cross-sectional study. METHODS: We studied relations between plasma concentrations of 25OHD, 1,25(OH)2D, and parathyroid hormone (PTH) in fasting plasma samples from 315 healthy postmenopausal women randomly selected from the local background population. RESULTS: P-1,25(OH)2D levels varied in a concentration-dependent manner with P-25OHD levels (P<0.001). Thus, P-1,25(OH)2D levels were the lowest in women with vitamin D insufficiency, i.e., P-1,25(OH)2D levels were reduced by approximately one-third in subjects with P-25OHD levels below 25 nmol/l compared with levels above 80 nmol/l (P<0.01). The association was most pronounced at P-25OHD concentrations below 80 nmol/l, whereas no major increase in P-1,25(OH)2D was observed at P-25OHD concentrations above 80 nmol/l. In multiple regression analysis, PTH was a minor although significant predictor of P-1,25(OH)2D levels. CONCLUSIONS: In normal postmenopausal women, the conversion of 25OHD to active vitamin D depends on the substrate concentration. Our data support that vitamin D insufficiency should be considered at P-25OHD levels below 80 nmol/l.

Annual intramuscular injection of a megadose of cholecalciferol for treatment of vitamin D deficiency: efficacy and safety data.

AIM: To evaluate the efficacy and safety of an annual intramuscular injection of cholecalciferol for vitamin D deficiency. DESIGN: Prospective open-label study. PARTICIPANTS: Five men and 45 women (mean age 66.3 years) with vitamin D deficiency who were given a single therapeutic intramuscular injection of 600 000 IU (15 mg) cholecalciferol (vitamin D(3)). OUTCOME MEASURES: Serum levels of calcium, creatinine, 25-hydroxyvitamin D(3) (25OHD(3)) and parathyroid hormone, as well as early morning 2-hour urine calcium/creatinine excretion index. Specimens were collected at baseline and after 4 and 12 months of therapy. Data are reported as mean +/- 1 SD. RESULTS: Vitamin D deficiency was severe (< 12.5 nmol/L) in one participant, moderate (12.5-24 nmol/L) in 14, and mild (25-49 nmol/L) in 35. Twenty-four participants (48%) had secondary hyperparathyroidism. Following intramuscular cholecalciferol injection, serum 25OHD(3) levels normalised in all participants and remained above 50 nmol/L throughout the study. Serum 25OHD(3) levels were significantly higher at 4 months (114 +/- 35 nmol/L), and 12 months (73 +/- 13 nmol/L) compared with baseline (32 +/- 8 nmol/L) (P < 0.001), increasing by an average of 128% over the 12 months. There was a corresponding decrease in serum parathyroid hormone levels at 4 months (6 +/- 3 pmol/L) and at 12 months (5.2 +/- 3 pmol/L), with a 30% decrease at 12 months from baseline (7.4 +/- 4 pmol/L) (P < 0.01). Primary hyperparathyroidism was unmasked in one participant at 4 months and mild hypercalcaemia (serum calcium, < 2.70 mmol/L) was noted in two participants (4%) at 12 months. Serum creatinine levels remained normal in all participants throughout the study, while increases in 2-hour urine calcium/creatinine excretion index were seen in 10 participants (20%) at 12 months, three of whom had had elevated values at baseline. CONCLUSIONS: Once-yearly intramuscular cholecalciferol injection (600 000 IU) is effective therapy for vitamin D deficiency. While this therapy appears to be safe, the potential for developing hypercalciuria needs to be examined in a large randomised controlled trial.