The effect of anticonvulsant therapy on serum levels of 25-hydroxy-vitamin D, calcium, and parathyroid hormone.

In 20 female patients treated for 2 to 37 years (mean :12) with anticonvulsant drugs, low serum levels of 25-hydroxy-vitamin D (25-OH-D; 6.4 +/- 3.2 ng/ml M +/- SD), relative hypocalcemia (9.2 +/- 0.4 mg/100 ml) and high levels of parathyroid hormone (PTH 277 +/- 165 pg/ml) were found compared to an age-matched control group (respectively 8.6 +/- 3.2 ng/ml, 9.6 +/- 0.3 mg/100 ml and 183 +/- 95 pg/ml) living in the same psychiatric clinic. A significant negative correlation was found between total duration of treatment and either serum 25-OH-D or serum calcium. After treatment with an oral vitamin D3 supplement (2000 IU/day) for 3 weeks, the serum 25-OH-D levels, although increased, remained lower than normal in the epileptic group and neither hypocalcemia nor their secondary hyperparathyroidism were corrected. These data confirm the occurrence of vitamin D deficiency in patients treated with anticonvulsant drugs resulting in hypocalcemia and secondary hyperparathyroidism.     

Serum insulin-like growth factor-I, insulin-like growth factor binding proteins, and bone mineral content in hyperthyroidism.

The mechanism by which thyroid hormones promote bone growth has not yet been elucidated. In vitro, thyroid hormones stimulate insulin-like growth factor-I (IGF-I) production by osteoblasts, which is important for the anabolic effects of the hormone on bone. To determine whether the IGF-I/IGF binding protein (IGFBP) profile is affected when thyroid hormone production is altered in vivo, we studied 36 women who had recently been diagnosed with hyperthyroidism (age: 29-67 years; 19 with Graves' disease, 17 with toxic nodular goiter) and 36 age-matched healthy women as controls. Serum IGF-I, and its binding proteins (IGFBP-3, IGFBP-4, and IGFBP-5), as well as bone mineral density (BMD) at the lumbar spine, femoral neck, and radius midshaft were measured before and 1 year after antithyroid (methimazole) treatment. Serum IGF-I levels were significantly increased in the hyperthyroid patients before treatment (214 +/- 18.2 ng/mL vs. 145 +/- 21.3 ng/mL; p < 0.05). There was no difference in IGF-I levels of patients with Graves' disease and toxic nodular goiter. Serum IGF-I concentrations returned to normal after treatment with methimazole. Serum IGFBP-3 and IGFBP-4 values were significantly elevated in the hyperthyroid group before treatment (3960 +/- 220 ng/mL and 749.7 +/- 53.1 ng/mL vs. 2701 +/- 180 ng/mL and 489.9 +/- 32.4 ng/mL; p < 0.05 and p < 0.01, respectively) and were reduced to those of controls after treatment. Serum IGFBP-5 of hyperthyroid subjects was not different from that of controls either before or after therapy. Serum free thyroxine showed a positive correlation with serum levels of IGF-I (r = 0.73, p < 0.05), IGFBP-3 (r = 0.59, p < 0.05), and IGFBP-4 (r = 0.67, p < 0.05) but not IGFBP-5. BMD at the radius midshaft was significantly lower in hyperthyroid patients at the start of the study and showed a positive correlation with serum IGF-I (r = 0.58; p < 0.001) and a negative correlation with IGFBP-4 (r = -0.61; p < 0.05). Radius BMD showed a 7.2% increase in the hyperthyroid group after 1 year of methimazole treatment, and the correlation between BMD and serum IGF-I disappeared. Our data indicate that thyroid hormones may influence the IGF-I/IGFBP system in vivo in hyperthyroidism. The anabolic effects of increased levels of IGF-I may be limited in hyperthyroidism due to the increases of inhibitory IGFBPs that can counteract the anabolic effects and contribute to the observed net bone loss.     

Plasma vitamin D metabolite concentrations in chronic renal failure: effect of oral administration of 25-hydroxyvitamin D3

The circulating concentrations of 1,25-dihydroxyvitamin D and 24,25-dihydroxyvitamin D are abnormally low in patients with chronic renal failure (CRF). To determine the importance of substrate (25-hydroxyvitamin D) concentration in this phenomenon, five patients with end stage renal disease treated with hemodialysis were given 25-hydroxyvitamin D3 (25-OH-D3) orally for 4 weeks. The serum concentration of 25-OH-D3 increased from a mean (+/- SEM) of 26 +/- 5 ng/ml immediately before therapy to a maximum of 108 +/- 5 ng/ml 4 weeks after beginning administration of 25-OH-D3. The concentrations of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), 24,25-dihydroxyvitamin D3 (24,25(OH)2D3), and 25,26-dihydroxyvitamin D3 (25,26(OH)2D3) increased from 6.6 +/- 0.8 pg/ml, 0.29 +/- 0.10 ng/ml, and 0.36 +/- 0.06 ng/ml, respectively, immediately before 25-OH-D3 administration to 21.7 +/- 2.2 pg/ml, 0.48 +/- 0.09 ng/ml; and 0.78 +/- 0.12 ng/ml, respectively, after 4 weeks of administration of 25-OH-D3. These results suggest that substrate availability may be an important determinant of the circulating concentrations of these metabolites in patients with CRF. It seems possible that the therapeutic effects of 25-OH-D3 administration to the CRF patient may be mediated through the normal actions of 1,25-dihydroxyvitamin D3, 24,25-dihydroxyvitamin D3, and perhaps other metabolites rather than through analog effects of 25-OH-D3.     

Clinical significance of competitive protein binding assay of 25-hydroxyvitamin D concentration

The level of serum 25-hydroxyvitamin D (25-OH-D3) was determined in 94 cases of healthy volunteers and 98 patients with various diseases. The mean level of the controls was 16.2 +/- 4.6 ng/ml (x /- S). The patients were divided into 5 groups, 1) Osteomalacia and rickets 42 cases, showing typical changes of bone in X-ray films. In 12 of them the disease was caused by vitamin D deficiency. The mean value of 25-OH-D3 was 3.3 +/- 2.0 ng/ml, being much lower than that of controls (P less than 0.001). In 14 cases of hypophosphatemia, 8 cases of renal tubular acidosis and 8 cases of renal insufficiency all complicated with osteomalacia the mean value of 25-OH-D3 was 17.9 +/- 11.4, 18.2 +/- 9.6 and 19.2 +/- 5.6 ng/ml (P greater than 0.05) respectively. 2) Intestinal malabsorption 18 cases. The mean level of 25-OH-D3 was 4.5 +/- 3.2 ng/ml (P less than 0.001). Some of them had hypocalcemia and/or secondary hyperparathyroidism. 2 showed osteoporosis and 1 osteomalacia. 3) Chronic liver disease 24 cases, the mean value of 25-OH-D3 was 6.2 +/- 5.6 ng/ml, being much lower than that of the controls (P less than 0.001). 4) 10 cases after taking anti-epileptic drugs had a mean level of 25-OH-C3 6.9 +/- 5.8 ng/ml (P less than 0.001). 1 had X-ray evidence of osteomalacia. 5) 4 cases of overdosage of vitamin D had a mean value of 110.3 +/- 22.5 ng/ml, being much higher than that of the controls (P less than 0.001). Competitive protein binding assay for measuring 25-OH-D3 is a simple and economic method. It is sensitive and specific as it provides distinct discrimination between healthy controls and patients with vitamin D deficiency or overdosage.     

Vitamin D deficiency in elderly patients in a general hospital

Serum 25-hydroxyvitamin D (25-OHD) levels were measured in 338 elderly patients admitted to the Geriatric Medicine Departments of a general hospital in Israel in the course of one year. The mean (+/- SD) serum 25-OHD levels were significantly lower (P less than .01) in the elderly patients (13.5 +/- 8.9 ng/mL) than in healthy young controls (24.7 +/- 6.1 ng/mL). One hundred ten patients (35.5%) were either vitamin D deficient (25-OHD less than 5 ng/mL) or had borderline serum levels of 25-OHD (5-9 ng/mL). The mean (+/- SD) serum 25-OHD concentration of patients who were completely mobile before hospitalization was 15.5 +/- 8.8 ng/mL (n = 239). In patients mainly immobilized but able to leave the house occasionally, it was 10.2 +/- 6.3 ng/mL (n = 84) and of bed-ridden patients, it was 5.2 +/- 3.2 ng/mL (n = 15). No correlation was found between serum 25-OHD levels and the patients' age or serum calcium, phosphorus, alkaline phosphatase, and albumin values. Thus, in order to detect vitamin D deficiency in the elderly, it is necessary to measure serum 25-OHD concentration. The results demonstrate that vitamin D deficiency is common among elderly patients even in sunny climates and indicate the need for development of effective programs of prevention and treatment.     

Sickle cell bone disease: response to vitamin D and calcium

Bone disease with osteoporosis and osteomalacia are common in sickle cell disease (SCD). Some patients have vitamin D deficiency and low bone mineral density (BMD). The role of vitamin D and calcium supplementation to restore bone health in SCD has not been well studied. In 14 adults with SCD, we measured 25(OH)D (25-hydroxyvitamin D) and BMD at the femoral neck, lumbar spine, and distal third of the ulna plus radius, along with markers of bone resorption (CTx; C-terminal component of pro-collagen type I) and bone formation (osteocalcin) before and after 12 months of vitamin D(2) and calcium carbonate treatment. Pretreatment, all patients were vitamin D deficient with a mean 25(OH)D level of 11.6 [corrected] +/- 4 [corrected] ng/ml, had low BMD at the lumbar spine (L-spine), 0.87 +/- 0.11 g/cm(2) (mean Z-score of -2.6 3 +/- 0.71 SD and T score of -2.31 +/- 0.75 SD), femoral neck, 0.8 +/- 0.18 g/cm(2) (mean Z-score -1.36 +/- 0.84, T-score -1.14 +/- 0.75), and the distal radius and ulna, 0.6 +/- 0.17 g/cm(2) (mean Z-score -1.18 +/- 0.79, T-score -1.01 +/- 0.74) and had elevated CTx (0.87 +/- 0.5 ng/ml) and osteocalcin levels (12.3 +/- 3.7 ng/mul). After treatment, all patients corrected their 25(OH)D level (34.6 [corrected] +/- 11 [corrected] ng/ml) (P < 0.001) with a 3.6% +/- 3.9% increase in BMD at the L-spine (P = 0.009), 4.6% +/- 8.5% increase at the femoral neck (P = 0.05) and 6.5% +/- 12.6% increase at the distal radius plus ulna (P = 0.09). CTx, osteocalcin, and PTH(i) levels were unchanged. Treatment of adult SCD with vitamin D and calcium can restore 25(OH)D levels to normal and improve BMD, but, markers of bone resorption remained unchanged. Screening for vitamin D deficiency and BMD in SCD patients seems warranted.     

Investigating the Efficiency of Vitamin D Administration with Buccal Spray in the Treatment of Vitamin D Deficiency in Children and Adolescents

Objective:The aim of this study was to evaluate the efficiency of a buccal spray form of vitamin D compared to single oral dose (stoss therapy) and oral drops therapy in the treatment of vitamin D deficiency.Methods:Ninety healthy children and adolescents (3-18 years) with vitamin D deficiency [serum level of 25-hydroxyvitamin D (25(OH) D) <12 ng/mL] were randomized to receive vitamin D3 buccal spray (2000 U, n=30, group 1) for six weeks, oral drops (2000 U, n=30, group 2) for six weeks and a single oral dose (300 000 U) vitamin D3 (n=30, group 3). Serum calcium, phosphorus, alkaline phosphatase, parathyroid hormone and 25(OH)D levels of the patients were measured at baseline and after the treatment on the 42^nd day.Results:All three groups had a significant increase in serum 25(OH)D concentrations (p<0.001). In group 1, baseline mean 25(OH)D was 8.0±0.41 ng/mL, which rose to 22.1 (17.8-28.2) ng/mL after treatment with a mean increase of 15.6±1.3 ng/mL. Similarly in group 2, baseline, post-treatment and mean increase in 25(OH)D concentrations were 7.9±0.45 ng/mL, 24.4 (20.6-29.6) ng/mL and 17.3±1.1 ng/mL while for group 3 these values were 7.6±0.47 ng/mL, 40.3 (29.4-58.4) ng/mL and 34.3±3.2 ng/mL, respectively.Conclusion:We conclude that vitamin D3 supplementation with buccal spray and oral drops is equally effective in terms of raising vitamin D concentrations in short-term treatment of vitamin D deficiency.     

Cutaneous vitamin D3 formation in progressive systemic sclerosis.

Progressive systemic sclerosis (PSS) is a predominantly dermal disorder which may be associated with epidermal atrophy. We investigated epidermal function in 8 patients with PSS and their healthy controls matched for age, sex and racial group. We measured the vitamin D3 photosynthetic response to whole body irradiation with ultraviolet light B (UVB). There were no significant differences in basal serum vitamin D3 levels (mean +/- SEM: PSS 1.2 +/- 0.2 ng/ml; controls 0.8 +/- 0.1 ng/ml; p greater than 0.1) or post UVB blood values (PSS 5.2 +/- 1.4 ng/ml; controls 6.9 +/- 1.1 ng/ml; p greater than 0.1); although the increases post-UVB were significant in both groups (p less than 0.01). In an additional group of 19 patients with PSS and their corresponding matched healthy controls, we performed determination of random levels of the active vitamin D metabolites, 25-hydroxyvitamin D (25-OH-D) and 1,25-dihydroxyvitamin D [1,25-(OH)2-D]. Similar levels were observed in both groups: 25-OH-D PSS 28 +/- 3 ng/ml, controls 29 +/- 3 ng/ml; 1,25-(OH)2-D PSS 27 +/- 2 pg/ml, controls 31 +/- 2 pg/ml (p greater than 0.1). None of the correlations between skin area involved and vitamin D3 formation or active circulating metabolites reached statistical significance (p greater than 0.1). We conclude that global epidermal synthesis of vitamin D is retained in PSS and, that the hepatic and renal vitamin D hydroxylating mechanisms function normally in that condition.     

The effects of vitamin D insufficiency in patients with primary hyperparathyroidism

PURPOSE: Differences in the prevalence of vitamin D deficiency may explain why the frequency of symptoms in patients with primary hyperparathyroidism varies geographically. This study was performed to determine the prevalence in the United States of low 25-hydroxyvitamin D levels among patients with mild primary hyperparathyroidism, and the effect of 25-hydroxyvitamin D status on disease severity. METHODS: We studied 124 patients with mild primary hyperparathyroidism. Biochemical, bone mineral density, and bone histomorphometric indices were compared among patients whose serurm 25-hydroxyvitamin D levels were in the lowest and highest tertiles. RESULTS: Serum 25-hydroxyvitamin D levels (mean +/- SD) were in the low range of normal (21 +/- 11 ng/mL, normal 9 to 52 ng/mL). Levels were below normal in 9 (7%) patients, and below the level suggested for vitamin D "sufficiency" (20 ng/mL) in 66 (53%) patients. Those with lowest 25-hydroxyvitamin D levels had the highest parathyroid hormone levels (low tertile 158 + 66 pg/mL versus high tertile 103 +/- 2 pg/mL, P <0.0001). Other evidence of more active hyperparathyroidism in those with low 25-hydroxyvitamin D levels included higher serum alkaline phosphatase activity (114 +/- 48 U/L versus 91 +/-35 U/L, P <0.03), lower serum phosphorus levels (2.7 +/- 0.4 mg/dL, versus 3.0 +/- 0.4 mg/dL, P <0.01), and greater bone mineral density at the lumbar spine (0.94 +/- 0.03 g/cm2 versus 0.83 +/- 0.03 g/cm2, P <0.05) reflecting the protective effects of parathyroid hormone on cancellous bone. They also had enhanced bone turnover on bone biopsy. Despite the expected differences in vitamin D metabolism in African-Americans, results did not differ by race. CONCLUSION: Vitamin D insufficiency or deficiency is common among patients with mild primary hyperparathyroidism. In these patients, the effects of primary hyperparathyroidism on biochemical, densitometric, and histomorphometric indices are more pronounced.     

Plasma vitamin D metabolites in parathyroid diseases (author's transl)

The basal values of plasma vitamin D metabolites were evaluated in patients with primary hyperparathyroidism (1 degree HPT, n = 31), hypoparathyroidism (HP, n = 7), pseudohypoparathyroidism (PHP, n = 4) and normal controls (n = 21). Plasma 25-hydroxyvitamin D (25-OH-D) in 1 degree HPT (9.0 +/0 7.3 ng/ml, mean SD) was significantly lower than that of normal controls (17.9 +/- 5.5ng/ml)(p less than 0.001), and in particular 1 degree HPT classified as the skeletal type showed extremely low value (4.7 +/- 4.6 ng/ml). Plasma 1, 25-dihydroxyvitamin D [1, 25-(OH)2D] was significantly higher in 1 degree HPT (69.1 +/- 31.4pg/ml)(p less than 0.001) and significantly lower in Hp (15.2 +/- 11.0 pg/ml) (p less than 0.001) compared to normal controls (37.2 +/- 13.8pg/ml), although there was no significant difference in PHP (22.3 +/- 17.5 pg/ml). Plasma 24, 25-dihydroxyvitamin D [24,, 25-(OH)2D] in 1 degree HPT (1.06 +/- 0.55 ng/ml) was significantly lower than that of normal controls (1.73 +/- 0.62 ng/ml) (p less than 0.05), and particularly 1 degree HPT classified as the skeletal type showed a marked low value (0.85 +/- 0.27 ng/ml), whereas no significant differences were seen in HP (1.84 +/- 0.46 ng/ml) or PHP (1.34 +/- 0.22 ng/ml). There were slight but significant correlations between either plasma 25-OH-D and 1, 25-(OH)2D (r = -0.350, p less than 0.05), or plasma 25-OH-D and 24, 25-(OH)2D (r = 0.356, p less than 0.05), or plasma 1, 25-(OH)2D and 24, 25-(OH)2D (r = -0.444, p less than 0.01) in all subjects. In addition, relationships between plasma vitamin D metabolites and other indicators of parathyroid function in all subjects were analyzed. There were positive correlations between plasma 1, 25-(OH)2D and serum Ca (r = -0.621, p less than 0.001) or urinary cAMP (r = -0.671, p less than 0.001) or nephrogenous cAMP (r = -0.689, p less than 0.001), while negative correlations were seen between plasma 1, 25-(OH)2D and serum P (r = -0.680, p less than 0.001) or %TRP (r = -0.663, p less than 0.001). On the other hand, there were negative correlations between plasma 24, 25-(OH)2D and serum Ca (r = -0.457, p less than 0.01) or urinary cAMP (r = -0.562, p less than 0.005) or nephrogenous cAMp (r = -0.561, p less than 0.005), and a positive correlation was seen between plasma 24, 25-(OH)2D and %TRP (r = 0.519, p less than 0.005). After parathyroidectomy, a distinct depression of plasma 1, 25-(OH)2D and reciprocal elevation of plasma 24, 25-(OH)2D were observed in 1 degree HPT. Furthermore, there was a clear elevation of plasma 24, 25-(OH)2D as well as plasma 1, 25-(OH)2D after treatment with maintenance doses of 1 alpha-OH-D3 or 1 alpha, 25-(OH)2D3 in HP and PHP. It is concluded that plasma vitamin D metabolites are very useful as the indicators of parathyroid function.     

Observations on serum 25-hydroxyvitamin D and calcium concentrations from wild-caught and captive neotropical bats, Artibeus jamaicensis

Most bats of the suborder Microchiroptera are nocturnal, actively avoid sunlight, and eat mineral-poor diets. In those bats previously studied with respect to mineral metabolism, extensive bone remodeling occurs, and it has been suggested that calcium has been an important constraint on reproduction. There have been no previous studies of vitamin D or its metabolites in microchiropteran bats with respect to calcium metabolism. Reported is the utilization of current advances for the determination of serum levels of the vitamin D metabolite 25-hyroxyvitamin D (25-OH-D) in a neotropical bat, Artibeus jamaicensis. Serum from wild-caught animals contained low levels of 25-OH-D (5.6 +/- 3.0 ng/ml, n = 8). Bats maintained on a vitamin-D-supplemented diet had higher serum 25-OH-D levels and when the diet containing vitamin D was discontinued, mean serum 25-OH-D levels declined significantly after 6 months. Serum calcium concentrations in wild-caught bats (8.5 +/- 0.4 mg%) showed very little variation and were not significantly different in any of the vitamin-D-supplemented animals. A pairwise correlation analysis between 25-OH-D and serum calcium levels revealed no linear correlation. The results indicate either that 25-OH-D does not appear to play a key role or that low levels of 25-OH-D may be adequate in regulating serum calcium levels in this bat.     

Vitamin D deficiency and changes in serum vitamin D levels with treatment among tuberculosis patients in South Korea

Background and objective: Vitamin D deficiency has been reported to be associated with the development of active tuberculosis (TB), but many discrepancies exist among studies. The aims of this study were to compare the frequency of vitamin D deficiency in a Korean population of TB patients and control subjects, and to monitor the changes in vitamin D levels during TB treatment. Methods: Patients with newly diagnosed TB were prospectively enrolled. In addition, healthy volunteers or patients with diseases other than TB were enrolled as controls. Baseline serum 25‐hydroxyvitamin D (25‐OHD) levels were measured in both groups and compared. In the TB patients, measurements of serum 25‐OHD were repeated 1 month after the initiation of treatment and again after completion of treatment. Results: In total, 116 patients with TB and 86 control subjects were recruited. The median 25‐OHD concentration was not different in TB patients at diagnosis (13.9 ng/mL; interquartile range (IQR) 8.80–21.8) compared with control subjects (13.2 ng/mL; IQR 9.6–19.3) (P = 0.97). The frequency of vitamin D deficiency (≤10 ng/mL) was also not different in TB patients (36.2%) compared with controls (27.3%) (P = 0.21). In TB patients, the median 25‐OHD concentration decreased significantly during treatment, to 12.5 ng/mL at 1 month and 11.0 ng/mL on completion of treatment (P = 0.01). Conclusions: Vitamin D levels do not appear to be associated with the development of TB in the Korean population. The median 25‐OHD concentration decreased after treatment for TB.     

Elevation of blood vitamin D2 levels does not impede the release of vitamin D3 from the skin.

The mechanism for the transfer of fat-soluble vitamin D3 from the avascular basal cellular layers of the epidermis to dermal capillaries and peripheral circulation is unknown, although vitamin D-binding protein (DBP) is thought to mediate this process. To evaluate the effect of increased occupancy of vitamin D carrier(s) on vitamin D3 removal from the skin, serial serum vitamin D2 and D3 concentrations were determined in three groups of six healthy volunteers given combinations of an oral dose of vitamin D2 (50,000 IU) and a fixed dose of UVB radiation (27 mJ/cm2). Serum vitamin D3 levels increased significantly following UVB (time effect, P < .01 by ANOVA), but the response remained unchanged after pretreatment with vitamin D2, increasing from 3 +/- 1 to 14 +/- 5 ng/mL (mean +/- SEM), versus UVB alone, 5 +/- 1 to 16 +/- 5 ng/mL. Elevation of serum vitamin D2 levels was also similar in the groups given vitamin D2 alone (< 1 to 64 +/- 8 ng/mL) and vitamin D2 + UVB (< 1 to 45 +/- 8 ng/mL). There was no time or treatment effect for changes in serum levels of 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, or (DBP) levels (P > .1). We conclude that vitamin D3 egress from the skin is not affected by elevated circulating vitamin D concentrations; thus, the cutaneous release of vitamin D is probably mediated by a protein such as DBP with a high carrying capacity for the vitamin.     

Vitamin D deficiency in children and adolescents

Objective Vitamin D deficiency is an important health problem in both developed and developing countries. Recent reports on the extraskeletal effects of vitamin D have led to increased interest in prevalence studies on states of deficiency/insufficiency of vitamin D. The aim of this study was to determine the frequency of vitamin D deficiency and insufficiency in children and adolescents residing in Ankara, Turkey and to investigate the factors associated with low vitamin D status. Methods: A total of 440 children and adolescents aged between 0 and 16 years were enrolled in this study. The subjects were divided into three groups according to their vitamin D status (deficiency ≤15 ng/mL; insufficiency: 15-20 ng/mL; sufficiency ≥20 ng/mL) and also according to their age (preschool<5 years; middle childhood: 5-10 years; adolescence: 11-16 years). Results: Overall, 40% of the subjects were found to have 25 hydroxy vitamin D [25(OH)D] levels of less than 20 ng/mL. The levels indicated a deficiency state in 110 subjects (25%) and insufficiency - in 66 (15%). The rate of vitamin D deficiency was higher in girls, regardless of age. 25(OH)D levels correlated negatively with age (r=-0.48, p<0.001), body mass index (BMI) (r=-0.20, p=0.001) and intact parathyroid hormone (iPTH) level (r=-0.31, p=0.001). A positive correlation was observed between 25(OH)D and serum ferritin levels (r=0.15, p=0.004). Conclusions: The high frequency of vitamin D deficiency in childhood (especially among adolescent girls) indicates a need for supplementation and nutritional support. Conflict of interest:None declared.     

Serum vitamin D2 and vitamin D3 metabolite concentrations and absorption of vitamin D2 in elderly subjects

The serum vitamin D2 and vitamin D3 metabolite concentrations and intestinal absorption of vitamin D2 were determined in healthy ambulatory and chronically institutionalized elderly subjects with normal renal function. The 25-hydroxyvitamin D (25OHD) concentrations were normal in all subjects (range, 8-43 ng/ml), although institutionalized subjects had a significantly lower mean value [19.2 +/- 2 (+/- SEM) ng/ml; P less than 0.01] compared with ambulatory subjects (25.3 +/- 2 ng/ml). All but one ambulatory subject had 25OHD3 as the major circulating form, whereas 25OHD2 was the major circulating metabolite in one third of the institutionalized subjects. The mean 1,25-dihydroxyvitamin D [1,25-(OH)2D] concentration in both groups was normal, but nine subjects had levels at or below the lower limit of normal despite normal 25OHD concentrations. Separate assay of 1,25-(OH)2D2 and 1,25(OH)2D3 revealed proportional distributions similar to those for 25OHD2 and 25OHD3. To study the effect of age on the intestinal absorption of vitamin D, we compared serum vitamin D2 concentrations after oral administration of 50,000 IU vitamin D2 in both healthy vitamin D-sufficient elderly subjects and young adults. We found no evidence of malabsorption of vitamin D in the elderly subjects. In summary, elderly subjects in New York, whether institutionalized or not, have normal serum 25OHD concentrations. However, while most elderly subjects have normal serum 1,25-(OH)2D levels, a significant proportion fail to produce normal concentrations of 1,25-(OH)2D, possibly due to age-related disturbances in renal synthesis of the hormone.     

Mild vitamin D deficiency and secondary hyperparathyroidism in nursing home patients receiving adequate dietary vitamin D.

OBJECTIVE: To compare the vitamin D metabolite and nutritional status of institutionalized elderly males with a noninstitutionalized control group. DESIGN: Case-control study. SETTING: Veterans Administration Medical Center Nursing Home (NH) in Richmond, Virginia. PATIENTS: Fifty-seven consecutive nursing home subjects were screened. After excluding blacks, those receiving anticonvulsants, glucocorticoids, or vitamin supplements, and those with liver or renal failure (creatinine greater than 1.5 mg/dL), 35 subjects were enrolled, and 22 completed the study. The noninstitutionalized control group (n = 18) consisted of consecutive volunteers, meeting the above criteria, from either a senior citizen group or a geriatric clinic. MEASUREMENTS AND MAIN RESULTS: The serum 25-hydroxy-vitamin D level in the NH residents was significantly lower than in community dwellers (17.4 +/- 5.2 ng/mL vs 31.2 pg/mL +/- 8.0 ng/mL, P less than 0.0001). No significant difference was demonstrated in 1,25-dihydroxyvitamin D levels (36.5 pg/mL +/- 10.5 in NH residents vs 42.0 pg/mL +/- 11.1 in controls). In the NH group PTH levels were inversely correlated with 25 OHD levels (P less than 0.008) and positively correlated with length of stay in the NH (P less than 0.016). There was no significant seasonal variation in vitamin D metabolite levels in the NH group. In the NH patients, the mean dietary intake of vitamin D was 232 +/- 378 mg/day and of calories was 1811 +/- 447 kcal/day. CONCLUSION: Despite apparently adequate calories, calcium, and vitamin D intake, hypovitaminosis D with compensatory PTH elevations occurs, regardless of season, in the nursing home population.     

Low serum concentrations of 1,25-dihydroxyvitamin D in human magnesium deficiency

The effect of magnesium deficiency on vitamin D metabolism was assessed in 23 hypocalcemic magnesium-deficient patients by measuring the serum concentrations of 25-hydroxyvitamin D (25OHD) and 1,25-dihydroxyvitamin D [1,25-(OH)2D] before, during, and after 5-13 days of parenteral magnesium therapy. Magnesium therapy raised mean basal serum magnesium [1.0 +/- 0.1 (mean +/- SEM) mg/dl] and calcium levels (7.2 +/- 0.2 mg/dl) into the normal range (2.2 +/- 0.1 and 9.3 +/- 0.1 mg/dl, respectively; P less than 0.001). The mean serum 25OHD concentration was in the low normal range (13.2 +/- 1.5 ng/ml) before magnesium administration and did not significantly change after this therapy (14.8 +/- 1.5 ng/ml). Sixteen of the 23 patients had low serum 1,25-(OH)2D levels (less than 30 pg/ml). After magnesium therapy, only 5 of the patients had a rise in the serum 1,25-(OH)2D concentration into or above the normal range despite elevated levels of serum immunoreactive PTH. An additional normocalcemic hypomagnesemic patient had low 1,25-(OH)2D levels which did not rise after 5 days of magnesium therapy. The serum vitamin D-binding protein concentration, assessed in 11 patients, was low (273 +/- 86 micrograms/ml) before magnesium therapy, but normalized (346 +/- 86 micrograms/ml) after magnesium repletion. No correlation with serum 1,25-(OH)2D levels was found. The functional capacity of vitamin D-binding protein to bind hormone, assessed by the internalization of [3H]1,25-(OH)2D3 by intestinal epithelial cells in the presence of serum was not significantly different from normal (11.42 +/- 1.45 vs. 10.27 +/- 1.27 fmol/2 X 10(6) cells, respectively). These data show that serum 1,25-(OH)2D concentrations are frequently low in patients with magnesium deficiency and may remain low even after 5-13 days of parenteral magnesium administration. The data also suggest that a normal 1,25-(OH)2D level is not required for the PTH-mediated calcemic response to magnesium administration. We conclude that magnesium depletion may impair vitamin D metabolism.     

Somatomedin-C/insulin-like growth factor I and vitamin D-induced growth

We measured serum somatomedin-C/insulin-like growth factor I (Sm-C/IGF-I) concentrations in vitamin D-deficient (-D) rats from 3-7 weeks of age to evaluate the role of Sm-C/IGF-I in the growth effects of vitamin D. To exclude effects of alterations in food intake, feeding patterns, and plasma minerals, controls included the following groups: pair fed (PFC; n = 10), low calcium diet (LCa; n = 10), meal fed (MFC; n = 10), and ad libitum fed (AdLC; n = 5). The -D, LCa, and PFC groups had similarly depressed growth rates and Sm-C/IGF-I concentrations. The growth and Sm-C/IGF-I concentrations of the MFC group were less than those in the AdLC group, but greater than those in the -D, PFC, and LCa groups. In all groups Sm-C/IGF-I concentrations correlated well with food intake, indicating that calorie intake, and not vitamin D deficiency or hypocalcemia, was the primary factor in reducing Sm-C/IGF-I. In the final 4 days of the study, half of the -D rats were given 1,25-dihydroxyvitamin D3 (2 ng/g BW;-D/repleted), while half of the PFC rats were given excess food during the meal period (PFC/refed). The weight gain of -D/repleted rats surpassed that of the -D rats treated with vehicle (P less than 0.05); similarly, the weight gain of PFC/refed rats exceeded that of the PFC rats (P less than 0.01). In contrast, the food intake and Sm-C/IGF-I levels of PFC/refed rats were greater than those in PFC rats (P less than 0.01), while the -D/repleted rats did not have significantly altered food intake or Sm-C/IGF-I levels. We conclude 1) that alterations in Sm-C/IGF-I concentrations of young growing -D rats are not directly related to lack of vitamin D, but, rather, to poor nutrition resulting from reduced food intake; and 2) that serum Sm-C/IGF-I is not a primary mediator of growth in -D/repleted rats since improved weight gain resulting from 1,25-dihydroxyvitamin D3 treatment can occur, acutely, without changes in serum Sm-C/IGF-I concentrations.     

Effects of elevated serum insulinlike growth factor-II on growth hormone and insulinlike growth factor-I mRNA and secretion

The insulinlike growth factors (IGF) appear to exert feedback control over their own production. In an effort to determine the physiologic mechanisms for this feedback modulation, we utilized a previously developed in vivo model in which rIGF-II secreting tumor cells are transplanted into immunodeficient rats to form IGF-II secreting tumors. The tumor-bearing rat have serum IGF-II concentrations sevenfold greater than those in controls (119 +/- 16 ng/mL [mean +/- SE] v 17 +/- 2 ng/mL, P less than .0001). Serum IGF-I concentrations were reduced among the tumor-bearing rats (438 +/- 42 ng/mL v 606 +/- 32 ng/mL, P = .002) and were negatively correlated with IGF-II concentrations (r = -.47, P = .025), suggesting that IGF-II suppressed the secretion of IGF-I. Increased serum IGF-II concentrations, however, did not affect basal growth hormone concentrations (tumor-bearing, 44 +/- 12 ng/mL; control 33 +/- 6 ng/mL, P = 0.96). The GH response to GH releasing factor was likewise similar in both groups. Moreover, pituitary GH mRNA level were not different in the two groups, suggesting that IGF-II does not have a significant effect on GH secretion in this in vivo model. There was no association between serum glucose and serum IGF-I or IGF-II concentrations. To examine the effect of IGF-II on IGF-I production from the liver, we measured IGF-I mRNA levels in a subset of animals. Despite these differences in serum IGF-I concentrations, the tumor-bearing rats did not have significantly lower liver IGF-I mRNA levels.(ABSTRACT TRUNCATED AT 250 WORDS)     

Factors affecting vitamin D status in outpatients with abdominal aortic aneurysm and peripheral artery disease- a single centre study

Background and aimsVitamin D (VD) deficiency is considered an important risk factor for the development of atherosclerosis and aortic aneurysms. The deficiency is claimed to enhance degeneration and remodeling of collagen and elastin fibers in the artery wall, leading to its weakening and progressive dilatation.This study aimed to assess vitamin D status, in outpatients with abdominal aneurysms (AAA) and peripheral artery disease (PAD) not treated with VD, and factors affecting serum 25-OH-D levels.Methods and resultsThis cross-sectional study involved 59 outpatients with AAA and 150 with PAD. AAA was defined as local dilation of the aorta diameter >30 mm in imaging. None of the patients was prescribed VD containing medicines. Serum 25-OH, iPTH, phosphorus and calcium levels were assessed in all study participants. VD status was categorized according to commonly used cut-offs for serum 25-OH-D (<20 ng/mL – deficiency, <30 ng/mL –insufficiency). Serum 25-OH-D levels were similar in patient with AAA and PAD [1-3Q: 26.2 (18.8–37.6) vs 21.8 (15.9–31.4) ng/mL; p = 0.30], with deficiency noted in 25.4% with AAA and 41.8% with PAD (p < 0.05). Multiple regression analysis revealed that VD deficiency was explained by past stroke episodes [OR = 2.80 (95%CI: 1.22–6.41)]. Secondary hyperparathyroidism was diagnosed in 1.7% of patients with AAA and 1.9% with PAD.ConclusionsThe frequency of VD deficiency in outpatient with AAA is not greater than in those with PAD. Past stroke episode is associated with an increased occurrence of VD deficiency in both outpatients with AAA and PAD other than sun exposure and diet.