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Item High‐dose Cholecalciferol Supplementation in Adults with Cystic Fibrosis(Wiley, 2019-09) Janzen, Kristin M.; Sakon, Colleen; Lehman, Angela; Sommer, Bekah; Brown, Cynthia; Medicine, School of MedicineIntroduction Despite the availability of consensus guidelines for the treatment of vitamin D deficiency, prospective trials are lacking to examine alternative dosing strategies for adult patients with cystic fibrosis (CF) who do not meet therapeutic goals with standard regimens. Objectives The primary objective of this study was to determine the efficacy of high‐dose cholecalciferol supplementation in increasing serum vitamin D (25‐OHD) levels in adult patients with CF. Methods Patients were eligible for inclusion if they were 18 years or older, had baseline 25‐OHD levels lower than 30 ng/ml, and were diagnosed with CF and pancreatic insufficiency. Patients were given a single dose of cholecalciferol 300,000 or 500,000 IU based on baseline 25‐OHD levels. Response was defined by 25‐OHD and ionized calcium levels at 3 months. At 6 months, responders received a second dose of the same strength, and nonresponders were given a weekly supplement of cholecalciferol 50,000 IU in addition to cholecalciferol 500,000 IU. A second 25‐OHD level was obtained at 9 months. Results Of the 46 patients enrolled, 32 patients (70%) completed the study. Baseline levels of 25‐OHD significantly increased over time in the per protocol population at 3 and 9 months. A total of 16 patients (50%) were considered nonresponders and required weekly supplementation. Conclusion A protocol using high‐dose cholecalciferol or high‐dose plus weekly cholecalciferol is safe and effective in treating adult patients with CF and pancreatic insufficiency.Item The Importance of Biologically Active Vitamin D for Mineralization by Osteocytes After Parathyroidectomy for Renal Hyperparathyroidism(ASBMR, 2019-11) Yajima, Aiji; Tsuchiya, Ken; Burr, David B.; Wallace, Joseph M.; Damrath, John D.; Inaba, Masaaki; Tominaga, Yoshihiro; Satoh, Shigeru; Nakayama, Takashi; Tanizawa, Tatsuhiko; Ogawa, Hajime; Ito, Akemi; Nitta, Kosaku; Anatomy and Cell Biology, School of MedicineHypomineralized matrix is a factor determining bone mineral density. Increased perilacunar hypomineralized bone area is caused by reduced mineralization by osteocytes. The importance of vitamin D in the mineralization by osteocytes was investigated in hemodialysis patients who underwent total parathyroidectomy (PTX) with immediate autotransplantation of diffuse hyperplastic parathyroid tissue. No previous reports on this subject exist. The study was conducted in 19 patients with renal hyperparathyroidism treated with PTX. In 15 patients, the serum calcium levels were maintained by subsequent administration of alfacalcidol (2.0 μg/day), i.v. calcium gluconate, and oral calcium carbonate for 4 weeks after PTX (group I). This was followed in a subset of 4 patients in group I by a reduced dose of 0.5 μg/day until 1 year following PTX; this was defined as group II. In the remaining 4 patients, who were not in group I, the serum calcium (Ca) levels were maintained without subsequent administration of alfacalcidol (group III). Transiliac bone biopsy specimens were obtained in all groups before and 3 or 4 weeks after PTX to evaluate the change of the hypomineralized bone area. In addition, patients from group II underwent a third bone biopsy 1 year following PTX. A significant decrease of perilacunar hypomineralized bone area was observed 3 or 4 weeks after PTX in all group I and II patients. The area was increased again in the group II patients 1 year following PTX. In group III patients, an increase of the hypomineralized bone area was observed 4 weeks after PTX. The maintenance of a proper dose of vitamin D is necessary for mineralization by osteocytes, which is important to increase bone mineral density after PTX for renal hyperparathyroidism.Item Vitamin D Status during Pregnancy and the Risk of Gestational Diabetes Mellitus: A Longitudinal Study in a Multiracial Cohort(Wiley, 2019) Xia, Jin; Song, Yiqing; Rawal, Shristi; Wu, Jing; Hinkle, Stefanie N.; Tsai, Michael Y.; Zhang, Cuilin; Epidemiology, School of Public HealthAims Emerging evidence suggests that maternal vitamin D status may be associated with gestational diabetes (GDM). However, the temporal relation remains unclear due to the lack of longitudinal data on vitamin D over pregnancy. We aimed to prospectively and longitudinally investigate vitamin D status during early to mid‐pregnancy in relation to GDM risk. Methods In a nested case‐control study of 107 GDM cases and 214 controls within the Fetal Growth Studies‐Singleton Cohort, plasma levels of 25‐hydroxyvitamin D2 and D3 (25(OH)D) and vitamin D binding protein were measured at gestational weeks 10‐14, 15‐26, 23‐31, and 33‐39; we further calculated total, free, and bioavailable 25(OH)D. Conditional logistic regression models and linear mixed‐effects models were used. Results We observed a threshold effect for the relation of vitamin D biomarkers with GDM risk. Vitamin D deficiency (<50 nmol/L) at 10‐14 gestational weeks was associated with a 2.82‐fold increased risk for GDM [odds ratio (OR) =2.82, 95% confidence interval (CI): 1.15‐6.93]. Women with persistent vitamin D deficiency at 10‐14 and 15‐26 weeks of gestation had a 4.46‐fold elevated risk for GDM compared to women persistently non‐deficient (OR=4.46, 95% CI: 1.15‐17.3). Conclusions Maternal vitamin D deficiency as early as the first trimester of pregnancy was associated with an elevated risk of GDM. The association was stronger for women who were persistently deficient through the 2nd trimester. Assessment of vitamin D status in early pregnancy may be clinically important and valuable for improving risk stratification and developing effective interventions for the primary prevention of GDM.