Changes in Vitamin D and Parathyroid Hormone Metabolism in Incident Pediatric Crohn's Disease

Department of Pediatrics, Yale-New Haven Children's Hospital, New Haven, Connecticut.
Inflammatory Bowel Diseases (Impact Factor: 4.46). 01/2013; 19(1). DOI: 10.1002/ibd.22969
Source: PubMed

ABSTRACT BACKGROUND: Prior studies of vitamin D metabolism in Crohn's disease (CD) did not include controls or examine changes following diagnosis. This study examined associations among 25-hydroxyvitamin D [25(OH)D], 1,25-dihydroxyvitamin D [1,25(OH)(2) D], and parathyroid hormone (PTH) levels in incident pediatric CD, compared with controls, and following diagnosis. METHODS: Serum vitamin D and PTH were measured at diagnosis (n = 78), 6, 12, and a median of 43 months (n = 52) later in CD participants, and once in 221 controls. Multivariate regression was used to examine baseline associations and quasi-least squares regression to assess subsequent changes. RESULTS: At diagnosis, 42% of CD participants were 25(OH)D-deficient (<20 ng/mL). The odds ratio for deficiency was 2.1 (95% confidence interval [CI]: 1.1, 3.9; P < 0.05) vs. controls, adjusted for age, race, and season. 1,25(OH)(2) D was lower in CD vs. controls (P < 0.05), adjusted for 25(OH)D, tumor necrosis factor alpha (TNF-α), and PTH. TNF-α was associated with lower 1,25(OH)(2) D (P < 0.05), and the positive association between PTH and 1,25(OH)(2) D in controls was absent in CD (interaction P = 0.02). Among participants with 25(OH)D <30 ng/mL, CD was associated with lower PTH (P < 0.05) vs. controls. Following diagnosis, 25(OH)D and 1,25(OH)(2) D improved (P < 0.001). At the final visit, 3% were 25(OH)D-deficient, PTH was no longer low relative to 25(OH)D, and 1,25(OH)(2) D was significantly elevated (P < 0.001) compared with controls. CONCLUSIONS: Incident CD was associated with 25(OH)D and 1,25(OH)(2) D deficiency and a relative hypoparathyroidism that resolved following diagnosis. Inflammatory cytokine suppression of PTH and renal 1-α-hyroxylase may contribute to these alterations. (Inflamm Bowel Dis 2012;).

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    • "The increase in PTH was followed by an increase in serum 1,25(OH) 2 D in 47% of the present T1DM patients, more often in those with moderate to severe periodontitis (64%) than in those with no or mild periodontitis (36%) (Fig. 2), implying that in these individuals increased PTH may have accounted for the increased hydroxylation of 25(OH)D into 1,25(OH) 2 D by 1 a-hydroxylase. Analogously, in the Crohn's disease studies an overall increase in 1,25(OH) 2 D was most likely related to PTH and restitution of 1a-hydroxylase activity after treatment of the disease (Prosnitz et al. 2013, Augustine et al. 2014). One reason for the lack of correlation between the changes in serum PTH and 1,25(OH) 2 D (Fig. 2) may be the relatively high proportion of subjects with no or mild periodontitis, who showed no significant PTH response. "
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    ABSTRACT: To study the association between periodontitis and serum parathyroid hormone (PTH) and the response of PTH to periodontal therapy in type 1 diabetic patients (T1DM). We also investigated the PTH-1,25(OH)2 D axis in the T1DM group. Periodontal health status was recorded in 54 periodontitis patients and 30 periodontally healthy controls (case-control data). Data were also collected from patients with type 1 diabetes mellitus at the baseline (n = 76) and after periodontal therapy (intervention data) (n = 53). Periodontitis was not associated with serum PTH in the case-control data or at the baseline of the intervention data. A post-therapy increase in serum PTH was found in 61% of the T1DM patients; in patients with moderate or severe periodontitis (n = 26) the average increase was 0.6 pmol/L (p = 0.016) and in patients with no or mild periodontitis (n = 27) 0.2 pmol/L (p = 0.250). In 47% of the T1DM patients, an increase in PTH was associated with an increase in serum 1,25(OH)2 D. An association between serum PTH and periodontal infection was found only after periodontal therapy in T1DM patients. This post-treatment response in serum PTH may partly explain the previously reported increase in serum 1,25(OH)2 D. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Journal Of Clinical Periodontology 07/2015; 42(8). DOI:10.1111/jcpe.12436 · 4.01 Impact Factor
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    • "Low parathormone levels were described in IBD patients in different studies [79-81]. Similarly to sodium fluoride, parathormone is a bone anabolic therapeutic agent. "
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    ABSTRACT: Diagnostic and therapeutic recommendations of the actual guidelines regarding inflammatory bowel disease (IBD)-associated bone loss are based on the experiences from the general osteoporotic population. Moreover, the fracture, as an end point of the bone loss has a different relationship to the bone mineral density in these patients compared to the general population. In this review we aimed to review the literature of the novel therapeutic possibilities regarding IBD-related bone loss. Dual-energy X-ray absorptiometry measurement should be performed in the presence of a risk factor such as age above 50, postmenopausal state, low trauma bone fracture in the history, corticosteroid therapy for more than 3 months or signs of hypogonadism. Serum Vitamin D and calcium levels should be measured in all patients. Supplementation is definitely needed in case of low serum calcium or Vitamin D concentrations and in patients under corticosteroid induction therapy. Short-term use of bisphosphonates in case of steroid induction was proved to be efficacious in preventing bone loss, but recent approvals do not include these indications. As fluorides and hormone replacement therapy have considerable side effects, their use in the young generation is also not acceptable.
    Annals of Gastroenterology 03/2013; 26(4):296-303.
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    ABSTRACT: Insufficient vitamin D status has been linked to autoimmune diseases, cancer and metabolic disorders, like obesity and insulin resistance. In vitro and animal studies suggest that vitamin D may play a crucial role in immune activation and inflammation. The relation between vitamin D and pro-inflammatory cytokines is not completely established. Furthermore, it is not known if the effect of vitamin D on entities of metabolic syndrome is mediated through its effect on cytokines or other biomarkers. The objectives of this study were to investigate if there is a relationship between vitamin D status and such pro-inflammatory cytokines as tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6) and high sensitive C-reactive protein (hs-CRP) in patients with overweigh and obesity. We also proposed that the intervention with high dose of cholecalciferol may have effect on the cytokine levels and result in corresponding changes in the measures of insulin resistance (HOMA-IR and QUICKI). Serum levels of IL-6, TNF-α and hs-CRP were measured in 332 overweight and obese subjects who completed a 1-year randomised intervention with either 40,000IU vitamin D (cholecalciferol) per week or 20,000IU vitamin D per week, or placebo. We found significant associations between IL-6, TNF-α, vitamin D and insulin resistance indices at baseline. One year intervention with vitamin D decreased serum IL-6 levels; however hs-CRP levels were significantly increased. Neither measures of insulin resistance, nor TNF-α were influenced by a 1-year vitamin D supplementation.
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