Long-Term Vitamin D Supplementation Improves Bone Mineral Density (BMD) in Patients with Sickle Cell Disease.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3800-3800
Author(s):  
Adeboye H. Adewoye ◽  
Michael F. Holick ◽  
Lillian C. McMahon ◽  
Qanli Ma ◽  
Martin H. Steinberg

Abstract Among the many complications of sickle cell disease (SCD) are osteopenia and osteoporosis. We and others have previously documented a high prevalence of low serum 25-OH vitamin D level with accompanying osteopenia and osteoporosis in patients with SCD; however the long-term effects of treatment on BMD have not been reported. We hypothesized that supplementation with oral vitamin D and calcium will result in an improvement in BMD and accordingly, treated 6 adult subjects with SCD for 12 months with oral supplementation with vitamin D and calcium and studied the effects of treatment on BMD. Subjects with serum 25-OH D levels <20 ng/ml were placed on 50,000 IU of oral vitamin D weekly for 8 weeks, followed by 50,000 IU every other week for 44 weeks; subjects also received 1000 mg of elemental calcium daily. We evaluated BMD at weeks 1 and 52. Subjects had a mean pre-treatment plasma 25-OH vitamin D of 9.1 ng/ml. BMD was abnormal in all subjects; 4 subjects had osteoporosis with a Z-score <-2.5, and 2 subjects had osteopenia with a Z-score −1.9 to −2.5 (in the lumbo-sacral vertebrae). All subjects had mildly elevated intact PTH levels which were within the reference range but declined further post-treatment. Following one year of treatment with vitamin D and calcium, we observed a mean post-treatment increase in BMD of 5.4% (p value <0.02) and a 176% increase in plasma 25-OH D level (from 9.1ng/ml to 28ng/ml; p value <0.009). All patients with SCD we have studied have hypovitaminosis D that in adults is associated with low BMD. In patients followed for one year who received supplementation with calcium and vitamin D, 25-OH D level increased in all and BMD improved in four of six subjects. These results suggest that this treatment regimen can be effective is restoring BMD. The reasons for apparent unresponsiveness in some patients must be further evaluated. Clinical trials to document the effectiveness of treatment for this ubiquitous problem should be instituted. Mean change in 25-OH vitamin D level Mean change in 25-OH vitamin D level Mean Change in BMD: Pre and Post Treatment Mean Change in BMD: Pre and Post Treatment

Bone ◽  
2020 ◽  
Vol 133 ◽  
pp. 115228
Author(s):  
Carmen Garrido ◽  
Eduardo J. Bardón-Cancho ◽  
Verónica de los Ángeles Fajardo-Sánchez ◽  
María Elena Cascón-Pérez-Teijón ◽  
Marina García-Morín ◽  
...  

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2482-2482
Author(s):  
Mehdi Nouraie ◽  
Caterina Minniti ◽  
Craig Sable ◽  
Andrew D. Campbell ◽  
Sohail R Rana ◽  
...  

Abstract Background: Sickle cell disease shares common complications such as vasculopathy and organ dysfunction involving the heart, the lungs, the liver and the kidneys with other hemolytic conditions. We hypothesized that a hemolytic vasculopathy may underlie some of these complications. Distinguishing whether a complication is due to hemolysis or to the degree of anemia has been a challenge. Methods: A prospective, multicenter study of 310 children and adolescents with sickle cell disease in steady state was conducted. The associations of measures of hemolysis and of hemoglobin concentration with disease complications were assessed. Principle component analysis was used to develop a hemolytic index from the measurements of reticulocyte count, lactate dehydrogenase, aspartate aminotransfersae and total bilirubin. In order to determine the independent associations of hemolysis with the clinical manifestations of sickle cell disease, we computed correlation coefficient of the hemolytic index with these manifestations that controlled for hemoglobin concentration. P values were adjusted for multiple comparisons. Results: Hemolysis and hemoglobin had no significant correlation with number of the severe pain episodes, acute chest syndrome and priapism. The hemolytic index correlated with history of stroke (r= 0.19, p=0.026), white blood cell count (r=0.22, p&lt;0.001), tricuspid regurgitation velocity (r=0.25, p&lt;0.001), left ventricular mass index (r=0.33, 0&lt;0.001), left ventricular internal diastolic z score (r=0.30, p&lt;0.001) and hemoglobin oxygen desaturation (r=−0.30, p&lt;0.001) but not independently with platelet count and creatinine and six-minute-walk Correlation of clinical outcomes with hemolytic index and hemoglobin concentration in sickle cell cases N Hemolytic index (r and P value) Hemoglobin (r and P value) Hemolytic index adjusted for hemoglobin (partial r and P value) 1 Square roots 2Natural Log 3Adjusted for patient’s height p values are adjusted for 13 comparisons. Number of severe pain episodes in the last year 283 −0.05 (0.4) 0.06 (0.3) −0.02 (0.7) History of acute chest or pneumonia 278 0.11 (0.09) −0.63 (&lt;0.0001) 0.06 (0.3) History of priapism History of stroke 137 0.13 (0.1) −0.63 (&lt;0.0001) 0.06 (0.5) 277 0.14 (0.3) 0.003 (1.0) 0.19 (0.026) Platelet count 1 283 0.32 (&lt;0.0001) −0.35 (&lt;0.0001) 0.11 (0.07) White blood cells 2 283 0.46 (&lt;0.0001) −0.47 (&lt;0.0001) 0.22 (&lt;0.001) Creatinine 1 282 −0.34 (&lt;0.0001) 0.45 (&lt;0.0001) −0.07 (0.2) Systolic blood pressure 283 0.01 (0.8) 0.16 (0.07) 0.14 (0.2) Tricuspid regurgitant jet velocity 264 0.35 (&lt;0.0001) −0.27 (&lt;0.001) 0.25 (&lt;0.001) Left ventricular internal diastolic diameter z score 282 0.53 (&lt;0.0001) −0.50(&lt;0.001) 0.30 (&lt;0.001) Left ventricular mass index1 215 0.51 (&lt;0.0001) −0.44 (&lt;0.001) 0.33 (&lt;0.001) O2 saturation 273 −0.49 (&lt;0.0001) 0.42 (&lt;0.001) −0.30 (&lt;0.001) Six-minute-walk (m)3 228 −0.03 (0.6) 0.17 (0.1) 0.07 (0.3) Conclusion: These observations support the hypothesis that a hemolytic vasculopathy independent of the degree of anemia contributes to the pathogenesis of stroke and pulmonary hypertension and to the development of increased systemic vascular resistance. They also raise the possibility that leukocytosis may in part serve as a predictor of poor outcome by its association with hemolysis. Therapeutic interventions that reduce the rate of hemolysis need to be studied for their potential benefit in decreasing the risk and severity of vasculopathy and the resulting organ damage.


Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4768-4768
Author(s):  
E. Leila Jerome Clay ◽  
Julia Brittain ◽  
Rupa Redding-Lallinger

Abstract Abstract 4768 Introduction: Vitamin D deficiency is known to be common in patients with sickle cell disease (SCD). Vitamin D is important in multiple aspects of health, including the cardiovascular, immune and skeletal systems and its effects are mediated through the vitamin D receptor. The systems affected by vitamin D are also perturbed by SCD. Vitamin D deficiency is common in SCD, but its contribution to disease manifestations is being investigated. Vitamin D modulates the immune response and may have an effect on the levels of increased inflammation seen in individuals with SCD. In children and young adults with SCD at UNC Hospitals, we sought to determine the prevalence of vitamin D deficiency and its association with inflammatory markers and the influence of VDR haplotype. We report here on vitamin D status and several markers of inflammation. Methods: We recruited pediatric and young adult SCD patients in their steady state attending routine periodic evaluations at the Pediatric and Adult Sickle Cell Clinics at the University of North Carolina Hospitals between February and June 2012. After consent, patients had their blood collected for inflammatory markers, 25-OH vitamin D and DNA. Patients with active pain crisis or recent illness were excluded. A chart review was done for the last 5 years to obtain SCD genotype, baseline white blood cell count, hemoglobin, platelets, calcium, phosphate and alkaline phosphatase. We measured inflammatory markers IL2, IL6, CD40L, TNFa, plasma VEGF and CD40L levels using ELISA (R&D Systems). At present only the VEGF and CD40L levels, along with baseline clinical laboratory data are available with the other inflammatory marker data expected shortly. Spearman's regression was used to examine potential correlations between continuous variables. A p value of < 0.05 was considered significant. P-values are considered nominal and are uncorrected for multiple analyses. Results: Vitamin D levels were measured in 78 patients, ages ranging from 2 to 26 years, with 55% males. The SCD genotypes were SS and Sb°Thal at 80%, SC and Sb+Thal at 20%. Thirty percent of patients were on hydroxyurea and ten percent of patients were on chronic exchange transfusions. Severe vitamin D deficiency (<10 ng/mL) was present in 18%, mild to moderate deficiency (10–24 ng/mL) in 54% and only 28% were sufficient (>25 ng/mL). VEGF mean was 110.1 pg/mL (SD 125.8). CD40L mean was 642.2 pg/mL (SD 378.2). For the group as a whole, there were no correlations between the inflammatory markers and 25-OH vitamin D levels. However, when the group who was vitamin D deficient (< 25 ng/mL) was examined (n=39), vitamin D levels were inversely correlated with platelet count (rho= −0.3596, p =0.0246). Platelet count was positively correlated with CD40L level (rho= 0.3176, p= 0.0488). VEGF and CD40L levels were positively correlated (rho= 0.4520, p= 0.0039). Vitamin D levels are negatively correlated with age (rho= −0.3794, p = 0.0172). Restricting the analyses by age and gender did not change the results, nor did removing the individuals on hydroxyurea or chronic transfusions. Discussion: As has been noted previously, vitamin D deficiency is very common in people with sickle cell disease, including this young population, with mean age of 14 years. Inflammation is common as well, as reflected by the markedly elevated CD40L levels as well as the high-normal distribution of white cell count and platelet count. VEGF levels in adults with SCD appear to be elevated although are quite variable; VEGF appears to be a marker of inflammation in this disease. Little is known about VEGF levels in children with SCD. No associations between vitamin D levels and CD40L or VEGF levels were seen, however an inverse correlation between vitamin D level and platelet count was found. As platelets are a marker of inflammation, this suggests that further investigation of the relationship between vitamin D deficiency and inflammation could be fruitful. We anticipate having data concerning vitamin D and IL2, IL6 and TNFa in this group in the near future, as well as the ability to stratify the individuals by VDR haplotype. Disclosures: Redding-Lallinger: Eli Lilly and Company: Research Funding.


2018 ◽  
Vol 40 (6) ◽  
pp. 458-461 ◽  
Author(s):  
Kristen M. Williams ◽  
Margaret T. Lee ◽  
Maureen Licursi ◽  
Gary M. Brittenham ◽  
Ilene Fennoy

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2924-2924 ◽  
Author(s):  
Jignesh Dalal ◽  
Brian R Lee ◽  
Matt Hall ◽  
Gerald M Woods ◽  
Ram Kalpatthi

Abstract Background Hospitalization is the major driver of health care utilization and costs in sickle cell disease (SCD) [Kauf et al. Am J Hematol 2009]. Allogeneic stem cell transplantation (alloSCT) is the only curative therapy available for sickle cell disease. However, it is a highly specialized, resource intense and expensive medical procedure. The objective of our study is to analyze the impact of alloSCT on the hospitalization patterns and resource utilization in children with SCD. Methods We used the Pediatric Health Information System (PHIS), a database of clinical and financial data from free-standing children's hospitals in the US. Using ICD-9 procedure and diagnosis codes, patients under the age of 21 who underwent alloSCT at one of the 26 PHIS hospitals from 2000-2011 were identified. We abstracted data on hospitalizations, alloSCT, resource utilization and costs. Pre and post alloSCT hospitalizations were calculated from day 0 (actual alloSCT procedure date) and does not include initial transplant hospitalization. The PHIS database provides an encrypted patient medical record number, thus we were able to follow patients over time. This allowed for a better visualization of the patient's hospitalizations trend over 11 years. Results From 2000 to 2011, 186 unique pediatric patients with SCD who underwent alloSCT were identified. The median hospital length of stay (LOS) and the median total hospital charges for the initial BMT hospitalization were 38 days (31, 51) and $143,000 ($109,000, $123,000) respectively. The mean hospitalization rate was significantly higher one year after alloSCT compared to one year before the transplantation (5.8 vs. 3.1 respectively, p=0.01). However, when we expanded the analysis over 2 years, there was no significant difference in the hospitalizations between the pre and post alloSCT groups (4.8 vs. 6.8 respectively, p=0.2). Similarly, the median total hospital charges per patient were significantly higher 1 year post-alloSCT compared to one year pre-alloSCT (Table 1) whereas it was not significant when analyzed 2 years pre/post-alloSCT (Table 2). In addition, both the hospitalization rate and costs decrease consistently for several years post alloSCT suggesting a long term benefit (Figure 1A & 1B). Conclusions AlloSCT for SCD increases the hospitalizations and costs in the first post transplantation year. This is consistent with the previous report of increased hospitalizations in the immediate post-transplant period of alloSCT for all pediatric disorders (Shulman et al. Pediatr Blood Cancer 2013). However, over the long term, alloSCT likely improves the quality of life (by decreasing the hospitalization rate) and economic burden of pediatric sickle cell population. Further studies associating various clinical morbidities (pre & post-transplant) and healthcare utilization are needed. Disclosures: No relevant conflicts of interest to declare.


Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1723-1723
Author(s):  
Jennifer Alison Busse ◽  
Kranthi Nandan Seelaboyina ◽  
Grace Malonga ◽  
Thomas Moulton

Abstract Introduction Promotion of chronic illness self-management is crucial to improve outcomes of children with sickle cell disease (SCD). Improvements in patient outcomes and quality of life as well as enhancement in health literacy and patient agency are also imperative. Through an event diary developed by the Bronx Lebanon Hospital Sickle Cell Program, our pediatric SCD patients are better able to track significant health events and health care appointments. This study seeks to validate the effectiveness of the patient event diary as a tool for improvement in self management, allowing for improvement in medication and clinic visit compliance, as well as in a reduction in number of emergency room visits. Additionally, the education section at the beginning of the diary has become an integral teaching tool and reference for patients and their families. It is our hypothesis that the event diary as an educational tool, a self management tool, and a tool for providers, will lead to better management of chronic illness and improved patient outcomes. Methods We utilized laboratory and demographic data from the Bronx Lebanon Hospital Center patient electronic medical record between July 2011 and July 2013. Our sample included a population of 50 sickle cell disease patients aged 0 to 21, median age being 7 years. Sickle cell disease types included SS (64%), SC (32%), Sβ+ thalassemia and Sβ0thalassemia (4%). We used a paired, two tailed t-test to assess patients’ medication compliance on vitamin D (22 patients) and hydroxyurea (14 patients) through 25-hydroxyvitamin D (25-OHD) and MCV (mean corpuscular volume) levels, respectively. Increased MCV was used as a proxy to indicate improved medication compliance in patients on hydroxyurea. We compared patients on hydroxyurea and vitamin D six months before receiving the event diary and six months after. Additionally, we compared compliance with hematology clinic visits one year before and one year after receiving the event diary. We also compared the number emergency room visits during the year before and the year after patients received the event diary. Results 25-OHD data from six months after receiving the event diary showed significantly improved compliance with vitamin D treatment (M = 47, SD = 20) as compared to six months before receiving the event diary (M = 26, SD = 15), t(20) = 2.1, p < 0.05. Additionally, there was a statistically significant improvement in MCV levels six months after receiving the event diary (M=101.6, SD=9.6), as opposed to six months before receiving it (M=97.7, SD=5.6), t(12)=2.2, p<0.05. When looking at patient hematology clinic appointment compliance, there was an improvement, however not statistically significant, in compliance with appointments between one year before (M=33.3%, SD=41.7%) and one year after patients received the event diary (M= 27.2%, SD=30.3%), t(17)=2.1, p=0.2. Emergency department visits did decrease, however not significantly, one year before receiving the event diary (M=1.8, SD=2.5) to one year after receiving the event diary (M= 1.3, SD=1.9), t(47)=2.0, p=0.17. Conclusions These data suggest the patient event diary has significantly improved patient self-management. We believe this effect is due to enhanced understanding of disease processes and increased confidence and skills in self-management of the disease. There is improved compliance with hydroxyurea and vitamin D, as well as a trend toward improvement in clinic visit compliance and decreased emergency room visits. The patient event diary is crucial to improved patient outcomes in the pediatric SCD population, and may be useful for other pediatric populations with chronic illness. It is a significant part of our current practice and our ability to teach and empower patients and their families to manage sickle cell disease while at home. Additionally, this tool allows for better management of patients by providers. The event diary helps to elucidate difficulties in patient self-management and gives better insight into complications patients are experiencing at home. In the future, we hope to see that with improved patient knowledge of sickle cell disease and self-management facilitated by use of the event diary, there will be significantly fewer emergency room visits, fewer hospital admissions, and most important, quality of life. Disclosures: Moulton: HRSA: Research Funding; New York State Grant: Research Funding.


Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 324-324
Author(s):  
Kestis Vaitkus ◽  
Vinzon Ibanez ◽  
Robert E Molokie ◽  
Angela Rivers ◽  
Joseph DeSimone ◽  
...  

Abstract Increased levels of fetal hemoglobin (HbF) lessen the severity of symptoms and increase the life span of patients with sickle cell disease. New and more effective strategies to increase HbF are needed because current therapies are ineffective in a significant proportion of patients. The lysine-specific demethylase, LSD1, an enzyme that demethylates Histone H3 mono- and dimethyl- K4 and K9 residues, is a component of the DRED co-repressor complex that represses the γ-globin gene (Cui et al, Mol Cell Biol 31:3298, 2011). Our laboratory has recently shown that RN-1, a pharmacological inhibitor of LSD1, increases γ-globin expression in sickle cell disease (SCD) transgenic mice (Rivers et al, Exp Hematol 43:546, 2015; Cui et al, Blood 126:386, 2015) and in baboons (Rivers et al, Haematol 101:688, 2016), widely acknowledge as the best animal model to test the activity of HbF-inducing drugs. To evaluate the safety and efficacy of RN-1, two normal, non-anemic baboons were treated for an extended period with RN-1 (PA8695, 264d; PA8698, 278d; 0.25mg/kg/d; 5d/wk, sc) and the effect on HbF, F cells, and hematological parameters evaluated weekly. Both animals exhibited weight gain (PA8695: 14.4%; PA8698: 20%) during the course of the study. F retics were increased 8-10 fold by the second week (d9) and were maintained at high levels throughout the course of the study (PA8695: 55.7±17.7% (mean±SD), median (M)=59.0%; PA8698: 56.4±14.5%, M=56.9%). F cell levels increased until d169 and were maintained thereafter at levels 18-25 times greater than pre-treatment (PA8695: 54.5±3.3%, M=54.2%; PA8698: 51.7±3.2%, M=51.4%). HbF levels also increased until d169 and were also maintained thereafter at levels 10-12 times greater than pre-treatment (PA8695: 12.8±1.7%, M=12.1%; PA8698: 11.4±1.4%, M=11.5%). Elevated levels of γ-globin chain synthesis were observed in the peripheral blood on multiple days (d162, d190, d267) of treatment (PA8695, 0.28±0.08 γ/γ+β;PA8698, 0.26±0.08 γ/γ+β). RT-PCR analysis showed that γ-globin mRNA levels were increased 9-22 fold (p<0.01) in FACS-purified CD105+ CD117+/- glyA+ BM erythroid precursor subpopulations of RN-1 treated baboons compared to normal baboons. Absolute neutrophil counts showed no overall decline compared to pre-treatment (PA8695: pre-treatment=2110/μL, post-treatment=3118±1452/μL, M=2765/μL; PA8698: pre-treatment=2690/μL, post-treatment=2936±696/μL, M=2460/μL) although variations were observed. In PA8695 the ANC declined below 1500/μL twice (1490, 1160) and five times (1250, 1410, 1420, 1330, 1000) in PA8595. Monocytes increased 2-3 fold in each animal (PA8695: pre-treatment=100/μL, post-treatment=252±97/μL, M=246/μL; PA8698: pre-treatment=161/μL, post-treatment=425±319/μL, M=347/μL). Hemoglobin (Hb), RBC, and hematocrit (HCT) levels exhibited small overall decreases during the course of treatment but remained within the normal range. Decreases in RBC, Hb, and HCT were associated with blood loss during menstruation (PA8695) and following an accidental laceration of the perineal swelling (PA8698). Rapid recovery was observed in both animals. Significant changes in MCV, MCH, and MCHC during treatment were not observed. Platelet levels decreased approximately 40% in each animal but nevertheless were maintained within the normal range (PA8695: pre-treatment=351 X 103/μL, post-treatment=236±64 X 103/μL, M=219 X 103/μL; PA8698: pre-treatment=224 X 103/μL, post-treatment=143±78 X 103/μL, M=119 X 103/μL). No significant differences in either PT or aPTT assays were observed compared to normal baboons. In vitro platelet activation assays performed to investigate effects on platelet function showed that the fraction of platelets expressing P-selectin (CD62P) on the surface following addition of thrombin was reduced 14% (p<0.02) and the level of CD62P expression reduced 46% (p<0.0001) in RN-1 treated baboons compared to controls. Normal platelet function was restored 10d post-drug. Elevated platelet activation is associated with the pathogenesis of sickle cell disease and inhibitors of platelet activation are currently in clinical trials. We conclude that long-term treatment with RN-1 increases and maintains elevated levels of HbF and F cells in normal baboons and is well-tolerated. Pharmacological inhibitors of LSD1 are therefore likely to be beneficial in patients with SCD. Disclosures Rivers: Acetylon: Research Funding. DeSimone:EpiDestiny: Consultancy, Other: patents around decitabine and tetrahydrouridine. Lavelle:Acetylon: Research Funding.


Nutrients ◽  
2022 ◽  
Vol 14 (2) ◽  
pp. 323
Author(s):  
Yuri Battaglia ◽  
Antonio Bellasi ◽  
Alessandra Bortoluzzi ◽  
Francesco Tondolo ◽  
Pasquale Esposito ◽  
...  

Vitamin D insufficiency has been associated with reduced bone mineral density (BMD) in kidney transplant patients (KTRs). However, the efficacy of vitamin D supplementation on BMD remains poorly defined, especially for long-term KTRs. We aimed to investigate the effect of native vitamin D supplementation on the BMD of KTRs during a 2-year follow-up. Demographic, clinical, and laboratory data were collected. BMD was evaluated with standard DEXA that was performed at baseline (before vitamin D supplementation) and at the end of study period. BMD was assessed at lumbar vertebral bodies (LV) and right femoral neck (FN) by a single operator. According to WHO criteria, results were expressed as the T-score (standard deviation (SD) relative to young healthy adults) and Z-score (SD relative to age-matched controls). Osteoporosis and osteopenia were defined as a T-score ≤ −2.5 SD and a T-score < −1 and a > −2.5 SD, respectively. Based on plasma levels, 25-OH-vitamin D (25-OH-D) was supplemented as recommended for the general population. Data from 100 KTRs were analyzed. The mean study period was 27.7 ± 3.4 months. At study inception, 25-OH-D insufficiency and deficiency were recorded in 65 and 35 patients. At the basal DEXA, the percentage of osteopenia and osteoporosis was 43.3% and 18.6% at LV and 54.1% and 12.2% at FN, respectively. At the end of the study, no differences in the Z-score and T-score gains were observed. During linear mixed model analysis, native vitamin D supplementation was found to have a negative nitration with Z-score changes at the right femoral neck in KTRs (p < 0.05). The mean dose of administered cholecalciferol was 13.396 ± 7.537 UI per week; increased 25-OH-D levels were found (p < 0.0001). Either low BMD or 25-OH-vitamin D concentration was observed in long-term KTRs. Prolonged supplementation with 25-OH-D did not modify BMD, Z-score, or T-score.


2013 ◽  
Vol 19 (1) ◽  
pp. 41-49 ◽  
Author(s):  
Anchalee Avihingsanon ◽  
◽  
Tanakorn Apornpong ◽  
Reshmie A Ramautarsing ◽  
Sasiwimol Ubolyam ◽  
...  

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