Finding the Optimal Dose of Vitamin D Following Roux-en-Y Gastric Bypass: A Prospective, Randomized Pilot Clinical Trial

Background  Vitamin D deficiency is common following bariatric surgery and is due to a combination of baseline deficiency and postoperative malabsorption. There are few prospective studies evaluating the appropriate dose of vitamin D to prevent and treat vitamin D deficiency following bariatric surgery. Methods  We evaluated three doses of vitamin D3 (800, 2,000, and 5,000 IU/day) in a prospective, randomized pilot trial of 45 patients undergoing Roux-en-Y gastric bypass. Serum 25 hydroxy Vitamin D (25OHD), intact PTH (iPTH), calcium, and urine calcium/creatinine ratios were measured at 6, 12, and 24 months postoperatively. Due to a high dropout rate at 24 months, we focus on the 12-month data. Results  At 12 months, the 800-, 2,000-, and 5,000-IU groups had a mean ± SD increase in 25OHD of 27.5 ± 40.0, 60.2 ± 37.4, and 66.1 ± 42.2 nmol/L, respectively (p = 0.09) with a maximum increase in each group of 87.4, 114.8, and 129.8 nmol/L. Forty-four percent, 78%, and 70% achieved 25OHD levels ≥75 nmol/L (p = 0.38). Results for the 6- and 24-month time points were similar to the 12-month results. Mean weight loss at 24 months of the study was not different among groups (p = 0.52). Serum calcium did not change significantly, and there were no cases of hypercalcemia or sustained hypercalciuria. Conclusions  Higher doses of vitamin D supplementation trend towards higher levels of 25OHD. Vitamin D replacement as high as 5,000 IU /day is safe and necessary in many patients to treat vitamin D deficiency following Roux-en-Y gastric bypass yet is still suboptimal in others.     

Vitamin D insufficiency and effect of cholecalciferol in children with chronic kidney disease

Vitamin D insufficiency is common in patients with chronic kidney disease (CKD) and may contribute to mineral bone disease. In a prospective interventional study, we estimated the prevalence of vitamin D insufficiency (serum 25-hydroxyvitamin D3 [25OHD] < 30 ng/ml), and examined the effect of high-dose (600,000 IU) cholecalciferol supplementation after 6 weeks on serum 25OHD and parathyroid hormone (PTH) levels in children with CKD stages 2–4. Forty-two children (86% boys) with a mean age of 7.7 ± 3.8 (range 2-–5) years were studied. Thirty-seven children (82.1%) had vitamin D insufficiency; 18 (42.8%) had 25OHD < 16 ng/ml. The median 25OHD increased significantly from 16.7 (95% CI 11.3, 19.8) to 46.2 (34.5, 44.6) ng/ml in patients with vitamin D insufficiency (P <0.001). The median PTH decreased significantly from 51.3 (95% CI 46.7, 71.5) to 37.1 (29.0, 54.6) pg/ml (P = 0.003). Nineteen patients (47.5%) had >30% reduction in the PTH after supplementation. Serum calcium, phosphorus, and estimated GFR did not change significantly. We conclude that vitamin D insufficiency is highly prevalent in children with CKD stages 2–4. High-dose cholecalciferol is safe and effective in correcting vitamin D insufficiency and results in a significant reduction in PTH levels in vitamin D-insufficient children.     

Skeletal and hormonal responses to sunlight deprivation in Antarctic expeditioners

Summary  Serum 25(OH)D levels decline without sunlight exposure. We studied 120 expeditioners to Antarctica to determine the skeletal and hormonal responses to sunlight deprivation. With emerging vitamin D insufficiency, serum calcium decreased, PTH increased, and bone loss at the proximal femur was observed. Baseline serum 25(OH)D levels >100 nmol/L prevented vitamin D insufficiency. Introduction  Vitamin D stores deplete without adequate sunlight exposure unless supplementation is provided. We studied 120 healthy adults who spent a year in Antarctica as a model for sunlight deprivation to define the timing and magnitude of the skeletal and hormonal responses to emerging vitamin D insufficiency. Methods  Fasting blood samples were assessed at baseline, 6 and 12 months for serum 25-hydroxyvitamin D (25(OH)D), osteocalcin (OC), bone formation (P1NP) and resorption (CTx), PTH and calcium. Lumbar spine and proximal femur BMD was measured using DXA. Differences over time were determined using repeated measures ANOVA. Percent changes were expressed as (Δ value/(value A + value B)/2) × 100. Relationships between outcome measures were determined using Spearman’s correlations. Results  Vitamin D insufficiency (<50 nmol/L) was observed in 85% of expeditioners by 6 months when serum calcium decreased and PTH increased (p < 0.01). By 12 months, OC increased by 7.4 ± 3.0% (p < 0.05), and BMD decreased by 1.0 ± 2.0% at the total proximal femur (p < 0.05). For those with vitamin D sufficiency at baseline (>50 nmol/L), sunlight deprivation produced vitamin D insufficiency within 4 months unless baseline values were >100 nmol/L. Conclusion  Supplementation may be necessary for expeditioners with limited access to UV light.     

Suppression of C-Terminal Telopeptide in Hypovitaminosis D Requires Calcium as Well as Vitamin D

We compared the effects of oral calcium and vitamin D separately and together on relevant variables in 22 postmenopausal volunteers with initial serum 25OHD levels below 60 nmol/L. Subjects were allocated randomly to two regimens: group 1 received 1 week of calcium 1,000 mg, followed by 7 weeks with additional vitamin D₃ 1,000 i.u. daily; group 2 received 7 weeks of D₃ 1,000 i.u. daily, followed by 1 week with additional calcium 1,000 mg. We measured serum calcium, phosphate, PTH, 25OHD, CTX, and ALP at baseline and after 1 and 8 weeks in group 1 and after 7 and 8 weeks in group 2. There were no significant changes in ALP from either vitamin D or calcium. Calcium caused significant elevation of serum 25OHD as well as major suppression of serum CTX, which could not easily be accounted for by suppression of PTH. Vitamin D caused no significant change in any variable except elevation of serum 25OHD. The suppressive effect of calcium (whether given first or second) on serum CTX was threefold greater than that of vitamin D (whether given first or second) (P < 0.001), although their suppressive effects on serum PTH were the same. Calcium and vitamin D yielded greater and more significant effects on all variables (except ALP) than either treatment alone. We suggest that calcium may elevate serum 25OHD by prolonging its half-life and that it may have an inhibitory effect on bone resorption independent of, or in addition to, its suppression of PTH.     

Efficacy of different doses and time intervals of oral vitamin D supplementation with or without calcium in elderly nursing home residents

Summary The effect of equivalent oral doses of vitamin D3 600 IU/day, 4200 IU/week and 18,000 IU/month on vitamin D status was compared in a randomized clinical trial in nursing home residents. A daily dose was more effective than a weekly dose, and a monthly dose was the least effective. Introduction It is assumed that equivalent daily, weekly or monthly doses of vitamin D3 equally influence vitamin D status. This was investigated in a randomized clinical trial in nursing home residents. Methods The study was performed in ten nursing homes including 338 subjects (76 male and 262 female), with a mean age of 84 (± SD 6.3 years). They received oral vitamin D3 either 600 IU/day, or 4200 IU/week, or 18,000 IU/month or placebo. After 4 months, calcium was added during 2 weeks, 320 mg/day or 640 mg/day or placebo. Outcome: serum levels of 25-hydroxyvitamin D (25(OH)D), parathyroid hormone (PTH) and bone turnover markers. Statistical approach: linear multilevel analysis. Results At baseline, mean serum 25(OH)D was 25.0 nmol/L (SD 10.9), and in 98%, it was lower than 50 nmol/L. After 4 months, mean serum 25(OH)D levels increased to 62.5 nmol/L (after daily vitamin D3 69.9 nmol/L, weekly 67.2 nmol/L and monthly 53.1 nmol/L, P < 0.001 between groups). Median serum PTH levels decreased by 23% (p < 0.001). Bone turnover markers did not decrease. Calcium supplementation had no effect on serum PTH and bone turnover. Conclusion Daily vitamin D was more effective than weekly, and monthly administration was the least effective.     

Rapid correction of low vitamin D status in nursing home residents

Summary  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 D₂ (ergocalciferol) treatment. Methods  This prospective study included 63 nursing home residents. The 25 with low vitamin D status (serum 25(OH)D ≤ 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)D₂, 25(OH)D₃, 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)D₃ remained stable in the comparison group, but declined (p < 0.0001) with D₂ 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 D₂ supplementation effectively and safely normalizes serum 25(OH)D in nursing home residents.     

Changes in 25-Hydroxyvitamin D3 to oral treatment with vitamin D3 in postmenopausal females with osteoporosis

Summary  This study reports on oral treatment with different doses of vitamin D3 ranging from 25 to 200 μg in females with 25-hydroxyvitamin D3 levels < 60 nmol/L screened for participation in an osteoporosis trial. A guidance to safely and efficiently achieve 25-hydroxyvitamin D3 levels > 60 nmol/L is presented. Introduction  The importance of vitamin D for skeletal health has been implemented in clinical trials in osteoporosis. The threshold of 25-hydroxyvitamin D for inclusion has changed from 30 to 60 nmol/L. This study reports on oral treatment with different doses of vitamin D3 in females with 25-hydroxyvitamin D3 levels < 60 nmol/L. Methods  In 131 postmenopausal females screened for participation in an osteoporosis trial, the 25-hydroxyvitamin D3 concentration was < 60 nmol/L. They were treated with 25 (n = 22), 50 (n = 19), 75 (n = 19), 100 (n = 41) or 200 μg (n = 30) of vitamin D3 daily for at least 10 days. Results  In the females treated with 25, 50, 75, 100 and 200 μg of vitamin D3 daily the 25-hydroxyvitamin D3 concentrations increased significantly from 32.4 ± 2.7 (mean ± SEM) to 50.8 ± 2.9, from 46.7 ± 2.8 to 65.8 ± 2.6, from 41.6 ± 2.7 to 67.4 ± 2.9, from 46.7 ± 1.4 to 64.4 ± 2.2 and from 42.1 ± 2.0 to 71.2 ± 2.8 nmol/L, respectively (p < 0.001). S-calcium increased significantly but within the reference range (p < 0.006). Conclusion  Oral vitamin D3 safely increased 25-hydroxyvitamin D3 concentrations in all females above 60 nmol/L. This study demonstrates how to achieve the new recommended 25-hydroxyvitamin D concentrations within the screening period of a clinical trial.     

Response of different PTH assays to therapy with sevelamer or CaCO<Subscript>3</Subscript> and active vitamin D sterols

Amino-terminally truncated parathyroid hormone (PTH) fragments are detected to differing degrees by first- and second-generation immunometric PTH assays (PTH-IMAs), and acute changes in serum calcium affect the proportion of these fragments in circulation. However, the effect of chronic calcium changes and different vitamin D doses on these PTH measurements remains to be defined. In this study, 60 pediatric dialysis patients, aged 13.9 ± 0.7 years, with secondary hyperparathyroidism were randomized to 8 months of therapy with oral vitamin D combined with either calcium carbonate (CaCO₃) or sevelamer. Serum phosphorus levels did not differ between groups. Serum calcium levels rose from 9.3 ± 0.1 to 9.7 ± 0.1 mg/dl during CaCO₃ therapy (p < 0.01 from baseline) but remained unchanged during sevelamer therapy. In the CaCO₃ and sevelamer groups, baseline serum PTH levels (1st PTH-IMA; Nichols Institute Diagnostics, San Clemente, CA) were 964 ± 75 and 932 ± 89 pg/ml, and levels declined to 491 ± 55 and 543 ± 59 pg/ml, respectively (nonsignificant between groups). Patients treated with sevelamer received higher doses of vitamin D than those treated with CaCO₃. The PTH values obtained by first- and second-generation PTH-IMAs correlated closely throughout therapy and the response of PTH was similar to both PTH-IMAs, despite differences in serum calcium levels.     

Increased Fracture Risk in Normocalcemic Postmenopausal Women with High Parathyroid Hormone Levels: A 16-Year Follow-Up Study

High PTH levels increase bone turnover and decrease bone mineral density (BMD). Low plasma 25-hydroxyvitamin D (25OHD) levels cause secondary hyperparathyroidism, but the relative contribution of low 25OHD and high PTH levels on risk of fracture is largely unknown. Within the cohort of women (n = 2,016) included in the Danish Osteoporosis Prevention Study (DOPS), we studied risk of fracture according to parathyroid status. Analyses were performed on effects of high PTH levels (i.e., in the upper tertile, ≥4.5 pmol/L) on risk of incident fractures at different 25OHD levels during 16 years of follow-up. Incident fractures were assessed using a nationwide hospital discharge register. In addition, effects of high PTH levels on BMD and vertebral fractures were assessed by DXA scans and spinal X-ray examination after 10 years of follow-up. High PTH levels were associated with a decreased body mass index, adjusted BMD, and an increased risk of any fracture (HR = 1.41, 95% CI 1.11–1.79) as well as an increased risk of osteoporotic fractures (HR = 1.59, 95% CI 1.20–2.10). Plasma 25OHD levels per se did not affect fracture risk, but high PTH levels were associated with an increased fracture risk only at 25OHD levels <50 nmol/L and 50–80 nmol/L. High PTH levels did not increase risk of fracture at 25OHD levels >80 nmol/L. In conclusion, PTH levels in the upper part or above the upper level of the reference interval increase risk of fracture in the presence of low vitamin D levels.     

Mineral Metabolism in Obese Patients Following Vertical Banded Gastroplasty

Background Bone disease has been described in patients after surgical treatment for obesity, but few studies have dealt with the impact of vertical banded gastroplasty on mineral metabolism. We have examined bone mineral metabolism in morbidly obese patients before and after 3 months after vertical banded gastroplasty without vitamin D supplementation. Methods Sixteen morbidly obese patients (14 women, 2 men) with a mean (±SD) age of 38 ± 9 years and a body mass index (BMI) of 47.1 ± 8.1 kg/m² were studied. No vitamin D supplementation was given. Body weight, fat mass, calcium, 25OHD, iPTH, bone remodeling markers, and leptin levels were measured at baseline and after weight loss. Results Mean weight loss was 28 ± 11 kg; BMI and body fat mass decreased by 20 and 35%, respectively. Bone resorption markers and albumin-corrected serum calcium increased after operation, whereas iPTH fell. Serum 25OHD levels rose. Leptin levels decreased. Serum iPTH was positively correlated with weight, BMI, and fat mass before operation (p < 0.05), and its decline after weight reduction was negatively associated with the increase in bone resorption markers (p < 0.01). Leptin concentration was correlated with BMI and body fat mass (p < 0.05) both before and after surgery. Conclusions Weight reduction obtained in morbidly obese subjects 3 months after vertical banded gastroplasty increases bone turnover markers and decreases PTH secretion. Serum 25OHD levels rose. Therefore, no reasons for a metabolic bone disease related to hypovitaminosis D were readily apparent. However, an increase in bone turnover, which is generally regarded as a potential risk factor for osteoporosis, was observed. Further work is needed to clarify the importance of this turnover increase in the long run.     

Low prevalence of vitamin D deficiency among adolescents with anorexia nervosa

Summary Fifty adolescents with AN and 200 healthy girls underwent vitamin D screening. Girls with AN reported exceptional compliance with vitamin D supplementation and PTH concentrations were lower. Vitamin D deficiency was less common in the group with AN, but when race was considered, the trend was no longer significant. Introduction The objective of this study was to determine whether patients with anorexia nervosa (AN) are more compliant with supplementation and have a lower prevalence of vitamin D deficiency than healthy controls. Methods Fifty adolescents with AN and 200 controls were compared using anthropometric and lifestyle data, serum 25-hydroxyvitamin D (25OHD) and parathyroid hormone (PTH) concentrations, and prevalence of vitamin D deficiency. Results The prevalence of deficiency (<20 ng/mL) was 2% in the AN group vs. 24% among controls (p = 0.003). 25OHD was similar among white participants with AN and white controls (39.5 vs. 36.0 ng/mL, p = 0.20), but higher than in non-white controls (20.6 ng/mL). Significantly more girls with AN reported vitamin D supplementation (86%) than the full control (14%) or white subgroup (27%) (p < 0.001). Participants with AN had lower PTH concentrations than controls, (27.8 vs. 47.4 pg/mL, p = 0.009), a trend that lost significance after age and race adjustment (41.7 pg/mL, p = 0.12). Conclusions Compared to healthy controls, adolescents with AN had a lower prevalence of vitamin D deficiency and PTH concentration. However, 25OHD and PTH concentrations were similar after adjustment for race and age. The trend of lower PTH levels in adolescents with AN, accompanied by exceptional compliance with supplementation, may have bone health implications for these patients. Research Support: Funded by NIH Grants RO1 HD043869 and MO1-RR-2172 to the Children’s Hospital General Clinical Research Center; Department of Defense (US Army, Bone Health and Military Readiness); and Project S-T71-MC-0000-10-S1-R0 from the Maternal and Child Health Bureau.     

Association between quantitative measures of skin color and plasma 25-hydroxyvitamin D

Summary  We examined the relationship between vitamin D and skin color measured by reflectance colorimetry at an exposed and un-exposed site in 321 people. Exposed but not unexposed skin color was associated with better vitamin D status. Sun-exposure was more important than natural skin color in determining vitamin D status in our population. Introduction  Vitamin D is obtained through UV synthesis in the skin where melanin limits its synthesis. Ethnicity is often used as a proxy for skin color, but skin color varies considerably. The relation between quantitative measures of skin color and plasma 25-hydroxyvitamin D (25OHD) concentration has not been well described. Methods  The aim of this study was to determine the association between constitutive (natural) and sun-induced skin color and 25OHD in a group of Pacific People (n = 87) and Europeans (n = 255) living in NZ (46°S) in summer. Plasma 25OHD was determined and sun-induced (outer fore-arm) and constitutive (upper inner-arm) measured by reflectance colorimetry. Results  Mean (SD) 25OHD was significantly higher in Europeans than Pacific People, 88 (31) nmol/L vs. 75 (34) nmol/L, respectively. Based on constitutive skin color, 35% of participants were very light, 45% light, 16% intermediate, 4% tanned, and 0% brown or dark. Skin color at the forearm but not constitutive skin color was a significant predictor of 25OHD. Each 10° lower skin color value at the forearm (more tanning) was associated with a 5 nmol/L higher 25OHD (P < 0.001). Conclusions  Tanning but not natural skin color was an important determinant of 25OHD. Further study is needed in a population with a higher proportion of darker skin people.     

Double Blind Randomized Control Study of Intramuscular Vitamin D3 Supplementation in Tropical Calcific Pancreatitis

Vitamin D deficiency is prevalent in chronic pancreatitis (CP), but the optimal route and dose of vitamin D supplementation are unknown. We evaluated the relative efficacy of two different doses of intramuscular (i.m.) vitamin D₃ in patients with CP and vitamin D insufficiency. In a double-blind randomized study, 40 patients with tropical calcific pancreatitis with serum 25-hydroxyvitamin D (25OHD) <75 nmol/L (mean 27.0 ± 14.5 nmol/L, <50 nmol/L in 90 %) were divided into three groups. Groups 1 and 2 received 600,000 IU (15,000 μg) and 300,000 IU (7,500 μg) i.m. cholecalciferol, respectively, while group 3 received i.m. saline. All groups received 1 g calcium and 500 IU (12.5 μg) vitamin D₃ orally daily and were studied for 9 months. The primary outcome was the proportion of patients with vitamin D sufficiency (25OHD >75 nmol/L) at 6 months. Vitamin D sufficiency was significantly different in the three groups (85, 29, and 0 % in groups 1, 2, and 3, respectively; p < 0.001). Mean 25OHD remained >75 nmol/L in months 1–6 in group 1 but reached a lower level (50–75 nmol/L) at these time points in group 2. At 6 months, serum alkaline phosphatase decreased significantly only in group 1 (230 ± 73 vs 165 ± 39 IU/L, p = 0.004). No patient in any group developed hypervitaminosis D or hypercalcemia. In conclusion, in patients with CP, a single i.m. injection of 600,000 IU was more effective at achieving vitamin D sufficiency over 6 months compared with 300,000 IU vitamin D₃. (Clinical Trials.gov number NCT00956839)     

Long-Term Effects of Neridronate and its Discontinuation in Patients with Primary Hyperparathyroidism

In patients with primary hyperparathyroidism (PHPT) not suitable for surgical correction, a skeletal protection with bisphosphonates is considered a reasonable option, but the long-term effects after treatment discontinuation are not well known. Sixty postmenopausal women with PHPT were given 400–600 IU vitamin D₃ daily and 100 mg neridronate IV every 2 months for 2 years with 2 additional years of follow-up without antiresorptive therapies. Bone mineral density (BMD) progressively rose by 6.7 ± 7.6% (SD) and by 2.9 ± 4.5% at the spine and femoral neck, respectively. During follow-up, mean BMD progressively fell, but after 2 years it was still 3.9 ± 5.5% higher than baseline values at the spine. Bone alkaline phosphatase and serum C-telopeptide of type I collagen decreased significantly within 6 months (28 and 49% versus baseline, respectively) and rose to baseline values within 6–12 months during follow-up. Serum PTH significantly rose from baseline during treatment, but it remained significantly higher than baseline during follow-up. The PTH changes were significantly correlated with serum 25-hydroxyvitamin D (25OHD) levels. In conclusion, in this study we observed that in patients with mild PHPT treatment with bisphosphonates is associated with the expected changes in bone-turnover markers and that the significant increases of both hip and spine BMD are partially maintained for at least 2 years after treatment discontinuation at the vertebral site. The marked increases in serum PTH levels, particularly in subjects with low 25OHD levels, persist after treatment discontinuation and this raises the suspicion that this might reflect a worsening of PHPT.     

Effect of high-dose vitamin D supplementation on bone density in youth with osteogenesis imperfecta: A randomized controlled trial

Osteogenesis imperfecta (OI) is a heritable condition characterized by fragile bones. Our previous studies indicated that serum 25-hydroxyvitamin D (25OHD) concentrations were positively associated with lumbar spine areal bone mineral density (LS-aBMD) in children and adolescents with OI. Here we assessed whether one year of high-dose vitamin D supplementation results in higher LS-aBMD z-scores in youth with OI. A one-year double-blind randomized controlled trial conducted at a pediatric orthopedic hospital in Montreal, Canada. Sixty patients (age: 6.0 to 18.9 years; 35 female) were randomized in equal numbers to receive either 400 or 2000 international units (IU) of vitamin D, stratified according to baseline bisphosphonate treatment status and pubertal stage. At baseline, the average serum 25OHD concentration was 65.6 nmol/L (SD 20.4) with no difference between treatment groups (p = 0.77); 21% of patients had results < 50 nmol/L. Vitamin D supplementation was associated with higher serum 25OHD concentrations in 90% of participants. The increase in mean 25OHD was significantly higher (p = 0.02) in the group receiving 2000 IU of vitamin D (mean [95% CI] = 30.5 nmol/L [21.3; 39.6]) than in the group receiving 400 IU (15.2 nmol/L [6.4; 24.1]). No significant differences in LS-aBMD z-score changes were detected between treatment groups. Thus, supplementation with vitamin D at 2000 IU increased serum 25OHD concentrations in children with OI more than supplementation with 400 IU. However, in this study where about 80% of participants had baseline serum 25OHD concentrations ≥ 50 nmol/L, this difference had no detectable effect on LS-aBMD z-scores.     

Seasonal Variation in the Deficiency of 25-Hydroxyvitamin D3 in Mildly to Extremely Obese Subjects.

Background  Vitamin D deficiency is a common finding in obese subjects even before any bariatric operation. However, most previous studies reporting on high rates of vitamin D deficiency in obese subjects have not systematically controlled for seasonal variations. Furthermore, the existence of seasonal variation in serum 25-hydroxyvitamin D₃ levels has not been well documented in obese subjects so far. Methods  Serum 25-hydroxyvitamin D₃ levels were measured in 248 obese subjects (body mass index: range, 30.1–68.9 kg/m²). Fat mass was determined using standard bioelectrical impedance analysis. Results  Serum 25-hydroxyvitamin D₃ levels decreased with the increasing body mass index and fat mass (both P < 0.001) and showed a marked variation across the seasons of the year (P < 0.001), which was not affected by the degree of obesity. According to the variation in absolute levels, the prevalence of vitamin D deficiency (<50 nmol/l) was 3.8-fold higher during winter than during summer (91.2% vs. 24.3%; P < 0.001). Conclusion  Data show a marked seasonal variation in absolute serum 25-hydroxyvitamin D₃ concentrations and prevalence of vitamin D deficiency in subjects with mild to extreme obesity. Considering the increasing number of studies reporting on vitamin D deficiency in obesity, the present finding points to season as a crucial factor that should not be neglected when assessing serum levels of this vitamin in obese subjects.     

Wintertime Vitamin D Deficiency in Male Adolescents: Effect on Parathyroid Function and Response to Vitamin D3 Supplements

The first part of this study consisted of an 18 month follow-up of the vitamin D status and parathyroid function in a group of 54 French male adolescents, aged from 13 to 16 years old and all pupils of a jockey training school. During the 18 month period four samplings were made, one every 6 months. The first was during September of the first year, the second and third during March and October of the second year, and the last in March of the third year. Therefore we had two main periods: summer and winter. The summer 25-hydroxyvitamin D (25(OH)D) concentrations were higher (71.6 ± 19.9 and 52.4 ± 16.5 nmol/l) than the winter ones (20.4 ± 6.9 and 21.4 ± 6.1 nmol/l). Conversely, the winter intact parathyroid hormone (iPTH) serum levels (4.18 ± 1.18 and 4.11 ± 1.35 pmol/l) were higher than the summer ones (2.44 ± 0.82 and 2.71 ± 0.71 pmol/l). At the two winter time points the 25(OH)D concentrations were lower than 25 nmol/l (10 ng/ml) in 72% (2nd year) and 68% (3rd year) of the adolescents. In the second part of the study we tried a vitamin D₃ supplementation procedure designed to maintain the 25(OH)D and iPTH postsummer serum levels throughout the winter. Pairs of male adolescents matched for height, weight and Tanner pubertal stage were randomly assigned to either vitamin D₃ supplementation (2.5 mg, i.e., 100 000 IU) administered orally at three specific periods (end of September, November and January) or no vitamin D₃ treatment (control subjects). Blood was collected just before the first intake of vitamin D₃ and 2 months after the last intake (March). The control subjects had blood drawn at the same time points. In the vitamin D₃-treated subjects, the concentrations of 25 (OH)D (55.3 ± 11.5 nmol/l) and of iPTH (3.09 ± 1.16 pmol/l) in March and September (53.8 ± 12.3 nmol/l and 2.75 ± 1.26 pmol/l) were not significantly different. In the control subjects, March 25(OH)D levels (21.0 ± nmol/l were low, with values below 25 nmol/l in 78% of subjects, and iPTH concentrations (3.97 ± 1.08 pmol/l) were significantly (p<0.001) higher than in September (2.91 ± 0.81 pmol/l). The constant vitamin D wintertime deficiency and wintertime rise in iPTH in adolescent French males throughout puberty has been demonstrated. In adolescents with low dairy calcium intakes, the vitamin D₃ treatment was sufficient to maintain 25(OH)D concentrations at their summer levels throughout winter and to prevent an excessive wintertime rise in iPTH levels. Received: 6 February 2001 / Accepted: 9 May 2001     

Serum 25-hydroxyvitamin D is associated with fracture risk only during periods of seasonally high levels in women with a high body mass index

Serum 25-hydroxyvitamin D (S-25OHD) is used to assess vitamin D status and is known to be affected by season and fat mass. Because these factors are often ignored when interpreting S-25OHD, assessment of vitamin D associations with disease outcomes may be distorted. We aimed to investigate the impact of season of blood draw and fat mass on the association of S25OHD with fracture risk. We enrolled 5000 women, mean ± SD age 68 ± 7 years, with dual-energy x-ray absorptiometry (DXA) scans and blood collection in a population-based cohort. Proportional hazards regression, stratified by season and fat mass, was used to determine hazard ratios (HRs) of fracture according to categories of S-25OHD. Our secondary exposures were serum 1,25-dihydroxycholecalciferol (1,25-(OH)₂ D₃), the most active vitamin D metabolite and plasma parathyroid hormone (P-PTH). During an average of 9.2 years of follow-up, 1080 women had a fracture. Women with S-25OHD <30 nmol/L drawn during sunny months (May–October) had a multivariable-adjusted fracture HR of 2.06 (95% CI, 1.27–3.35) compared with those with S-25OHD >60 nmol/L; those with S-25OHD 30–40 nmol/L had an HR of 1.59 (95% CI, 1.12–2.26). In contrast, S-25OHD drawn during November through April was unrelated to fracture risk. The increased risk with low sunny season S-25OHD was seen only among women with body mass index (BMI) ≥25 kg/m² or fat mass index (FMI) ≥9.8 kg/m². High fat mass and low S-25OHD were independently related to lower S-1,25-dihydroxycholecalciferol, which itself predicted fracture risk with samples collected during the sunny season. Irrespective of season, P-PTH was unrelated to fracture risk. We conclude that S-25OHD is associated with fracture risk only if drawn during periods of seasonally high levels in women with a high BMI. These results have implications for the evaluation of vitamin D status and can explain the lack of effect seen with vitamin D supplementation in many fracture trials. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).     

Association between vitamin D status and serum parathyroid hormone concentration and calcaneal stiffness in Japanese adolescents: sex differences in susceptibility to vitamin D deficiency

There is currently insufficient information on serum 25-hydroxyvitamin D (25OHD) and parathyroid hormone (PTH) concentrations, and bone mineral status in healthy adolescents to allow reference values to be set. This study aimed to provide comparable data on vitamin D status in Japanese adolescents and to assess sex differences in susceptibility to vitamin D insufficiency. Serum 25OHD and PTH concentrations were measured in 1,380 healthy adolescents (aged 12–18 years). Subjects completed a questionnaire on exercise history, diet, and lifestyle factors. Calcaneal stiffness was evaluated by quantitative ultrasound. Serum 25OHD concentrations in boys and girls were 60.8 ± 18.3 and 52.8 ± 17.0 nmol/L, respectively. Approximately 30 % of boys and 47 % of girls had suboptimal 25OHD concentrations (<50 nmol/L). Serum PTH concentration was negatively correlated with serum 25OHD concentration in boys, but negatively correlated with calcium intake rather than serum 25OHD in girls. In contrast, the increment in calcaneal stiffness as a result of elevation of serum 25OHD was higher in girls than in boys. As vitamin D deficiency is common in Japanese adolescents, it was estimated that intakes of ≥12 and ≥14 μg/day vitamin D would be required to reach 25OHD concentrations of 50 nmol/L in boys and girls, respectively. Moreover, the results of the present study indicate that vitamin D deficiency has a greater association with calcaneal stiffness in girls than in boys.