Low 25-OH Research Articles

P49 An unusual cause of transient migratory bone oedema: fibroblast growth factor-23 secreting a mesenchymal tumour

Abstract Background Fibroblast growth factor-23 (FGF-23) is a phosphate regulator primarily expressed by osteocytes. Excess FGF-23 leads to decreased hydroxylation of 25-hydroxyvitamin D and poor renal phosphate reabsorption. This leads to hypophosphatemia and represents a rare cause of osteomalacia, resulting in bone oedema and stress fractures. Methods A 57-year-old man with known skin psoriasis presented with a two-year history of left foot and ankle pain. On examination, he had chronic dactylitis of the big toe and extra-articular features included skin psoriasis on the scalp, elbows, knees, and nail pitting. Serum inflammatory markers were normal, and autoimmune screens for RF, anti-CCP and HLA-B27 were negative. Bilateral foot and ankle X-rays showed no bony abnormality. This was diagnosed as likely psoriatic arthritis and MRI showed talar bone oedema, felt to be related to inflammatory arthritis. Symptoms settled well on non-steroidal anti-inflammatories. However, he presented with focal distal tibial swelling and pain, two months later. There was no history of trauma, Repeat MRI2 showed proximal migration of bone oedema with stress fractures of the left posterior talus and distal tibial metaphysis. Bloods tests showed low phosphate, elevated PTH, normal adjusted calcium, raised ALP and low 25-OH vitamin D. DEXA scan confirmed osteoporosis of the hip. The patient was commenced on bisphosphonate with 25-hydroxyvitamin D and phosphate supplementation. Despite this, the patient continued to have migratory joint pain affecting the ankle, hip and sacroiliac joints. Methotrexate was started for psoriasis and whilst his skin improved, his pain remained and further MRI showed left talar and right neck of femur insufficiency fractures. Results Although taking vitamin D3 supplementation, he remained hypophosphateamic 0.5mmol/L. Myeloma screen and PET FDG were normal. However, he was noted to have an increased fractional urinary phosphate excretion indicating poor renal phosphate reabsorption. One possible cause of this is elevated FGF-23, which was confirmed with FGF-23 assay (include levels and normal range). The patient underwent PET Ga-DOTATE imaging, utilising a tracer specific for somatostatin receptors found on neuroendocrine tumours. This showed a T9 pedicle lesion and a CT-guided biopsy confirmed a mesenchymal tumour as the cause of FGF-23 secretion, resulting in TBMO and insufficiency fractures. The patient has become asymptomatic on calcitriol and phosphate supplementation. He is now being considered for radiofrequency ablation therapy. Conclusion This case illustrates the need for a thorough investigation of symptomatic, treatment-refractory hypophosphataemia. Although mild hypophosphatemia could indicate adult-onset rickets, rarer causes such as FGF-23 secreting tumours should be considered. These tumours are notoriously difficult to locate; Ga-DOTATE PET is probably superior to other imaging modalities including FDG-PET in isolating mesenchymal tumours. Disclosures K. Fisher None. S. Melath None. S. Patel None.

A170 VITAMIN D IN IBD PATIENTS – A RETROSPECTIVE REVIEW

Abstract Background Vitamin D is a critical factor in bone remodelling, calcium absorption and may promote anti-inflammatory cytokines in the gut. Inflammatory bowel disease (IBD) is associated with a reduction in serum Vitamin D levels and a chronic inflammatory state, both of which are strong risk factors for bone density loss affecting IBD patients. Despite European and North American IBD maintenance guidelines for Vitamin D monitoring and bone density scans, there are limited North American investigations into factors influencing serum Vitamin D levels in the IBD patient population specifically. Aims We investigated whether patient demographics, disease severity indexes and/or inflammatory markers were linked to low serum Vitamin D levels in our IBD patients. We also established the extent of Vitamin D serum deficiencies and supplementation rates in our IBD patients. Methods A retrospective chart review of a single clinician’s practice at London Health Science Centre, Victoria Hospital, over the past 20 months, was performed to: 1) assess the frequency of low serum 25-OH Vitamin D (25-OH D) in the IBD patient population and 2) determine whether patient disease severity was linked to lower 25-OH D levels. A multivariate regression analysis was performed assessing Crohn’s Disease (CD) or Ulcerative Colitis (UC) patient factors: age, sex, disease duration, seasonality, current pharmacologic treatments, past surgeries, CD Activity Index, UC Mayo score, C-reactive protein, and fecal calprotectin (Fcal) level. Results 175 IBD patients had at least one 25-OH D measurement with 71 patients actively on Vitamin D therapy. Of UC and CD patients who were not on Vitamin D therapy, 63% (17/27) and 79% (61/77) were 25-OH D deficient, respectively. 25-OH D levels in the CD population was associated with Vitamin D supplementation (regression coefficient [RC] 23.99, 95% confidence interval [CI] 14.54 to 33.45), summer season ([RC] 9.90, [CI] 0.56 to 19.24), and past bowel resection ([RC] -10.61, [CI] -20.48 to -0.76). 25-OH D levels in the UC population was associated with Vitamin D supplementation (regression coefficient [RC] 47.23, 95% confidence interval [CI] 27.62 to 66.83), and Mayo severity scores ([RC] -23.01, [CI] -41.82 to -4.20). Fcal (78 patients) was inversely associated with 25-OH D levels but the trend was not significant. Conclusions Overall, 25-OH D levels were lower in both the UC and CD patient populations relative to the already deficient Canadian population. However, IBD patients are responsive to Vitamin D supplementation. Tools with more objective evidence of disease severity such as UC Mayo score and fcal should be prioritized for identifying the IBD population requiring supplementation. Funding Agencies None

Evolution of bone mineral density, bone metabolism and fragility fractures in Spinal Muscular Atrophy (SMA) types 2 and 3

With recent advances in the treatment of Spinal Muscular Atrophy (SMA), there is a strong need to increase knowledge on the involvement of organs and systems outside the central nervous system. We investigated bone metabolism, bone mineral density (BMD) and fractures, and their possible correlation with age and motor capacities. Thirty-two children with SMA (27 type 2, 5 type 3), mean age 40 ± 32.3 months, underwent two evaluations at an 18-month interval (V1 and V2). Twelve of these children also underwent a third evaluation at month 36 (V3). Diet, bone metabolism, BMD, X-rays, and motor function (by the Hammersmith Functional Motor Scale Expanded – HFMSE – and the Upper Limb Module – ULM) were assessed. At V1, 25-OH vitamin D3 (25OH D) therapy was started, and dietary calcium intake adjusted according to the recommended dietary allowance. Low 25OH D levels and asymptomatic vertebral fractures were mainly observed at V1. At all visits, bone resorption markers were higher than normal. At V2 and V3, decreased BMD was observed. Higher spine BMD values at follow-up were associated with HFMSE score >12 at baseline (p<0.03). This study suggests that even young children with SMA are at risk of severe bone fragility. Further investigations of the molecular mechanisms leading to altered bone metabolism in SMA could help identify novel therapeutic targets and establish better guidelines for bone fragility management.

The importance of parathormone in determining the deficiency of vitamin D

Abstract Background To evaluate the association of parathormone with vitamin D and to find a threshold value for vitamin D. Material and methods This descriptive study included 11,753 (2352 males, 9401 females) patients from University hospital and 25-OH vitamin D and PTH levels were evaluated. Results The mean parathormone level was 49.33 ± 22.39 pg/mL. 18.7% of the patients had hyperparathyroidism. 77.4% of the patients had low 25-OH D vitamins. There was a negative correlation between serum parathormone levels and 25-OH vitamin D levels. The minimum 25-OH vitamin D level to keep PTH below 65 pg/mL was 18.5 ng/mL. Conclusion For determining the threshold value of 25 OH vitamin D, serum PTH levels should be assessed with 25-OH vitamin D levels.

SAT-231 A Case of Small Cell Ovarian Cancer, Hypercalcemic Type, in Pregnancy

Introduction Hypercalcemia in pregnancy is uncommon. Immediate evaluation and management is key to manage hypercalcemia in pregnancy to prevent maternal and fetal complications. Some common causes include primary hyperparathyroidism, vitamin D toxicity, and hyperthyroidism. An uncommon cause of hypercalcemia in pregnancy is small cell ovarian cancer, hypercalcemic type (SCCOHT). Case 26 year old woman, presented to the emergency department at 22 weeks of gestation with complaints of generalized weakness, fatigue, increased thirst, constipation, and intermittent right lower quadrant abdominal pain for 2 weeks. Past medical history was significant for polycystic ovarian syndrome. Labs revealed elevated albumin-corrected calcium: 17.5 mg/dl (8.7-10.5 mg/dl), low serum phosphorus: 2.1 mg/dl (2.7-4.5 mg/dl), low 25-OH vitamin D: 13 ng/ml (30-96 ng/ml), 1,25-OH Vitamin D: 44 pg/ml (20-79 pg/ml), and elevated PTHrP: 14 pmol/L (<2 pmol/L). The intact PTH was 12 pg/ml (9-77 pg/ml). TSH < 0.010 uIU/ml (0.4-4.0 uIU/ml) and free T4: 1.91 ng/dl (0.71-1.51 ng/dl). TSI & TPO levels were low. CA 125 was elevated: 135 U/ml (0-30 U/ml). Patient received IV hydration, IV furosemide, calcitonin, and pamidronate at the time of admission for management of hypercalcemia. MRI revealed large right adnexal mass measuring 19 cm; mostly solid but with cystic components. She underwent exploratory laparotomy with salpingo-oophorectomy. On post-op day 1 albumin corrected calcium decreased to 11.3 mg/dl. Repeat PTHrP on post-op day 3 decreased to 0.5 pmol/L. Pathology was notable for SCCOHT. At 27 weeks gestation, patient went into spontaneous labor and delivered. Following the delivery, she was started on chemotherapy with etoposide/cisplatin. After completion of one cycle of chemotherapy, her albumin corrected calcium level was 10.3 mg/dl. She was able to tolerate her first cycle of chemotherapy well and was in stable condition at the time of discharge. Discussion This case demonstrates an uncommon cause of hypercalcemia in pregnancy. Although rare (1% of all ovarian tumors), SCCOHT is an aggressive tumor with poor prognosis. SCCOHT should be considered as a differential in a young woman presenting with severe hypercalcemia. Majority of patients with SCCOHT have hypercalcemia, primarily mediated through the production of PTHrP, however our patient also had measurable calcitriol level possibly contributing to hypercalcemia. References Münstedt K, Estel R, Dreyer T, Kurata A, Benz A. Small Cell Ovarian Carcinomas - Characterisation of Two Rare Tumor Entities. Geburtshilfe Frauenheilkd. 2013;73(7):698-704.

Vitamin D Status Modifies the Response to Indoor Particulate Matter in Obese Urban Children with Asthma

Indoor fine particulate air pollution (PM2.5) is linked to asthma morbidity; however, whether vitamin D status influences individual susceptibility to airborne exposures is unclear. We aimed to determine if vitamin D modifies the effects of indoor PM2.5 on asthma symptoms in urban children. A total of 120 children aged 5 to 12 years with physician-diagnosed asthma were evaluated at baseline and every 3 months for 9 months. Indoor PM2.5, serum 25-hydroxy vitamin D (25-OH D) levels, and asthma symptoms were simultaneously assessed at each time point. Adjusting for confounders, generalized estimating equations assessed the 3-way interaction effects of 25-OH D, obesity, and PM on asthma symptoms. Children were of mean (standard deviation [SD]) age 9.7 (2.2) years, 36% were obese, and 95% self-reported black race. Mean (SD) PM2.5 indoor exposure was 38.2 (42.9) μg/m3 and 25-OH D was 19.1 (7.5) ng/mL. Three-way interaction models demonstrated significantly greater PM2.5-associated effects on daytime asthma symptoms only among obese childrenwith low 25-OH D levels (odds ratio [OR]PM2.5= 1.26, P= .049 at vitamin D= 15.5 ng/mL, increasingly stronger PM effects at levels <15.5 ng/mL). In homes with increased PM2.5, higher 25-OH D was associated with decreased symptom odds (eg, ORVitamin D= 0.87; P= .049 at PM2.5= 52.5 μg/m3, increasingly protective effects >52.5 μg/m3) among obese children. Among obese urban children with asthma, low individual 25-OH D enhanced adverse respiratory effects associated with indoor PM2.5. In high PM2.5 environments, 25-OH D was protective against asthma symptoms. Optimizing vitamin D status in children may help reduce asthma morbidity driven by indoor air pollution.

Clinical Phenotypes, Comorbidities, and Exacerbations according to Serum 25-OH Vitamin D and Plasma Fibrinogen Levels in Chronic Obstructive Pulmonary Disease.

BackgroundAlthough vitamin D deficiency is prevalent in patients with chronic obstructive pulmonary disease (COPD), the influence of vitamin D deficiency on COPD has not been fully established. Moreover, the inflammation process is associated with vitamin D deficiency in the general population. Therefore, this study aimed to determine whether clinical phenotypes, comorbidities, and exacerbation rates are affected by the level of plasma fibrinogen, well studied by an inflammatory marker in COPD patients, and 25-hydroxy (25-OH) vitamin D.MethodsThis retrospective study analyzed patients with COPD whose inflammatory marker levels, especially plasma fibrinogen and 25-OH vitamin D levels, had been examined. A correlation analysis was conducted for inflammatory markers and 25-OH vitamin D. Clinical characteristics, comorbidities and exacerbation rates were compared among four groups based on plasma fibrinogen concentrations (threshold, 350 mg/dL) and 25-OH vitamin D levels (threshold, 20 ng/mL).ResultsAmong 611 patients with COPD, 236 were included in the study. The levels of inflammatory markers had no statistical correlation with the serum 25-OH vitamin D levels. The four groups showed no statistically significant differences in age, sex, smoking history, inhaler use, and severity of comorbidities. Patients with high plasma fibrinogen concentrations and low 25-OH vitamin D levels had lower lung function, higher severity index, and higher annual rate of severe exacerbations 12 months before (0.23/year) and after (0.41/year) the measurement of 25-OH vitamin D levels than did the other patients.ConclusionOur findings suggested an interaction between vitamin D deficiency and COPD. The measurement of plasma fibrinogen concentrations could help identify a severe phenotypic group among patients with vitamin D deficiency.

PARATHYROID HORMONE, BUT NOT 25-HYDROXI VITAMIN D, SERUM LEVELS ASSOCIATE WITH ALDOSTERONE-TO-RENIN RATIO AND NOCTURNAL MEAN BLOOD PRESSURE VARIABILITY

Objective: To assess the association between serum parathyroid hormone (PTH) or vitamin D serum levels with blood pressure, aldosterone-to-renin ratio, and target organ damage in a series of hypertensive patients. Design and method: Observational cross-sectional study of hypertensive patients who undergone 24-hour ambulatory blood pressure monitoring (24-h ABPM), in whom plasma aldosterone, plasma aldosterone-to-renin ratio, PTH and 25-OH D serum levels were available. Blood pressure (BP) was measured by 24-hour ABPM. BP was assessed as average real variability. Renin-angiotensin-aldosterone axis status was assessed through plasma aldosterone levels and aldosterone-to-renin ratio. Electrocardiography, echocardiography and urine albumin-to-creatinine ratio were used to evaluate left ventricular hypertrophy and renal damage, respectively. Patients with primary hyperparathyroidism were excluded. Results: We enrolled 170 consecutive patients (median age [IQR] -year), 52 [42–64]; 48.2%, female). In comparison with patients with normal PTH serum levels (<88 pg/ml), those with high PTH serum levels (>88 pg/ml) showed a significantly increase in plasma aldosterone-to-renin ratio [mean ± SD] (37.8 ± 46.6 vs. 20.7 ± 27.0; p = 0.032), and nocturnal pulse pressure (56.3 ± 17.9 vs. 50.6 ± 13.1 mm Hg; p = 0.029). Furthermore, when compared with patients in the PTH 1st quartile, those in the 4th PTH quartile showed significantly higher nocturnal systolic BP (129.5 ± 25.6 vs. 119.9 ± 14.4 mm Hg; p = 0.038), plasma aldosterone (204.9 ± 128.4 vs. 153.8 ± 88.7 pg/ml; p = 0.037), plasma aldosterone-to-renin ratio (36.4 ± 45.8 vs. 18.9 ± 24.5; p = 0.033), and nocturnal mean BP variability (8.9 ± 4.4 vs. 7.1 ± 1.7 mm Hg; p = 0.016). Differences in aldosterone-to-renin ratio and nocturnal mean BP variability remained significant after adjusting by age, gender, renal function and ACE/ARB therapy in multivariate analysis. No such differences were observed in patients with vitamin D deficiency (25-OH D < 20 ng/ml), when compared with patients with normal vitamin D serum levels. Conclusions: High PTH, but not low 25-OH D serum levels associate with increased aldosterone-to renin ratio and elevated nocturnal mean blood pressure variability. Our results might explain, in part, the lack of consistent clinical benefit of vitamin D supplementation on high blood pressure and cardiovascular risk. We suggest that serum PTH status should be considered in trials searching for cardiovascular benefits from vitamin D supplementation in patients with hypovitaminosis D.

Neurofibromatosis-associated Malabsorption

We report on a case of a young woman who presented with anemia secondary to malabsorption in the setting of neurofibromatosis with intestinal involvement. A 25-year-old woman presented with symptomatic iron deficiency anemia. There was no history of menorrhagia or pregnancy and she was eating a regular diet. For the prior 18 months, she suffered from diarrhea and weight loss. Her family history was significant for both her mother and brother having neurofibromatosis type 1. She, herself, had been previously diagnosed with neurofibromatosis based on café au lait spots. Her exam was significant for several café au lait spots, a 2.5cm neurofibroma on the chest, a firm yet non-tender abdomen, and a body mass index of 17.3. Labs revealed a microcytic anemia of 6.4g/dL with an associated ferritin of 2.7ng/mL. Further laboratory testing revealed a low serum copper of 29μg/dL, hypoalbuminemia of 2.0g/dL, and a low 25-OH vitamin D at 6.1ng/mL. Thiamine, vitamin E, vitamin B12, folate and IgA tissue transglutaminase were normal. A CT scan showed multiple segments of severely thickened jejunal and ileal loops. Some areas contained polypoid luminal masses. A conglomeration of low-density masses was noted throughout the small bowel mesentery (Figure 1). The terminal ileum and proximal duodenum were not involved. A subsequent diagnostic push enteroscopy revealed markedly dilated lacteals in the jejunum (Figure 2). Jejunal biopsies confirmed diffuse mucosal involvement by neurofibroma with associated dilated lacteals (Figure 3). This led to a diagnosis of small bowel neurofibromatosis-associated malabsorption. Neurofibromatosis type 1 is an autosomal dominant condition associated with gastrointestinal tumors in up to 25% of cases.1 Neurofibromatosis causing lymphatic obstruction of the extremities with resultant lymphedema is well reported. Neurofibromatosis involving the small bowel may present with occult bleeding, intussusception, or constipation.3-5 In the case described here, infiltration of the mesentery as well as the small bowel with neurofibromatosis resulted in dilated lacteals, associated hypoalbuminemia, as well as multiple vitamin deficiencies. The patient's anemia and copper improved with parenteral iron and copper supplementation, but her hypoalbuminemia and diarrhea persisted. Because of extensive small bowel involvement, surgical resection was deferred and she was referred to a nutritionist for dietary manipulation.Figure: CT demonstrating segments of thickened jejunal and ileal loops, polypoid luminal masses. and a conglomeration of low-density masses throughout the small bowel mesentery.Figure: Push enteroscopy revealing markedly dilated lacteals in the jejunum.Figure: Jejunal biopsies showing diffuse neurofibroma with dilated lacteals.

Study to determine whether SNPs in CYP17A1, ESR1, and TNRC9 loci correlate with increased breast cancer risk and serum 25-OH vitamin D levels.

e13086 Background: Low serum 25-OH vitamin D (25-OH Vit.D) level is associated with a higher risk of breast cancer. Many single nucleotide polymorphisms (SNP) are associated with breast cancer risk, although the mechanisms underlying this association in most cases remain unclear. We attempted to address this issue by determining whether specific SNPs were correlated with breast cancer-associated biomarkers (BM). Methods: We analyzed estrogen receptor (ER)-positive breast cancer patients treated between Jan 2011 and Dec 2014. We measured serum testosterone and 25-OH Vit.D in pre- and post-menopausal women, and also measured estradiol in the latter group. We genotyped 7 individual SNPs both in premenopausal and postmenopausal women. We then looked for correlations between BMs and SNPs in all three genotypes (homozygotes of major alleles, heterozygotes and homozygotes of minor alleles) using the Kruskal-Wallis test. For each SNP locus associated with a trend or significant effect with regard to BM levels, a t-test was then applied to determine which of the two genotypes was responsible for the effect. Results: Four hundred thirteen women were enrolled (163 premenopausal patients, and 250 postmenopausal patients). There was a trend difference between CYP17A1 rs743572 and 25-OH Vit.D (p = 0.0888), ESR1 rs204210 and 25-OH Vit.D (p = 0.0534) in premenopausal women, and a significant difference between TNRC9 rs3803662 and 25-OH Vit.D (p = 0.026) in postmenopausal women. Among premenopausal women, 25-OH Vit.D levels were significantly lower in those with the high-risk rs743572 genotype TC when compared with TT individuals (19.2 +/- 6.7 ng/ml vs 22.9 +/- 8.7 ng/ml; p = 0.0125). Similarly, 25-OH Vit.D was significantly lower in women with the high-risk rs204210 genotype AG when compared with GG individuals (19.1 +/- 6.9 ng/ml vs 21.7 +/- 6.4 ng/ml; p = 0.0219). In postmenopausal women, 25-OH Vit.D was significantly lower in women with the high-risk rs3803662 genotype GG than those with the AA genotype (20.5 +/- 9.2 ng/ml vs 24.4 +/- 8.0 ng/ml; p = 0.0104). Conclusions: Specific SNPs in CYP17A1, ESR1, and TNRC9 genes may modulate breast cancer risk due to their influence on serum 25-OH Vit.D levels.

Bone mineral density and bone metabolic markers' status in children with neurofibromatosis type 1.

Neurofibromatosis type 1 (NF1) is a multisystem disorder characterized by progressive manifestations, which is inherited in an autosomal dominant manner. The majority of patients with NF1 experience a diffuse, significant reduction in bone mass over time, with osteoporosis, osteopenia in the absence of severe scoliosis, or gross bone deformities. This study aimed to determine the bone mineral density (BMD) status, evaluate bone metabolism, and to determine the relevant factors in children with NF1. The study population included 33 pediatric NF1 patients (20 males and 13 females). Bone metabolic markers, such as total calcium, phosphorus, magnesium, alkaline phosphatase, parathyroid hormone, and 25-OH vitamin D, the urinary calcium/creatine ratio were measured. In addition, BMD was measured at both the lumbar spine (LS) and the femoral neck in all the patients. All the patients had a low 25-OH vitamin D level, but it was significantly lower in the females than in the males (p<0.009). Overall, 18.2% of the patients had skeletal abnormalities. The lumbar Z-score was ≤2 in 21.2% of the patients, whereas the femoral neck Z-score was ≤2 in 9.1%. The urinary calcium/creatine ratio was significantly higher in the female than in the male patients (p<0.027). In all, six patients had skeletal abnormalities. It is widely known that bone mineral metabolism markers and BMD are significantly affected in NF1 patients; however, the present study did not identify any effective parameters that could be used to predict skeletal abnormalities, or diagnose early osteoporosis and osteopenia in pediatric NF1 patients.

Usefulness of calcaneal quantitative ultrasound stiffness for the evaluation of bone health in HIV-1-infected subjects: comparison with dual X-ray absorptiometry.

ObjectivesWith the development of effective treatments and the resulting increase in life expectancy, bone mineral density (BMD) alteration has emerged as an important comorbidity in human immunodeficiency virus type-1 (HIV-1)-infected individuals. The potential contributors to the pathogenesis of osteopenia/osteoporosis include a higher prevalence of risk factors, combined antiretroviral therapy (cART)-exposure, HIV-1 itself and chronic immune activation/inflammation. Dual-energy X-ray absorptiometry (DXA) is the “gold standard” technique for assessing bone status in HIV-1 population.MethodsWe conducted a cross-sectional study to investigate bone mineral status in a group of 158 HIV-1-infected subjects. The primary endpoint was the feasibility of calcaneal quantitative ultrasound (QUS) as a screening tool for BMD. All subjects were receiving stable cART and were virologically suppressed (HIV-RNA <37 copies/mL) from at least 12 months. Calcaneal QUS parameters were analyzed to obtain information on bone mass and microarchitecture. The results were compared with those obtained by DXA.ResultsNo correlations were found between DXA/QUS parameters and demographic or HIV-1-specific characteristics, also including cART strategies. In the univariate analyses BMD, QUS indexes, and Fracture Risk Assessment Tool scores conversely showed significant associations with one or more demographic or HIV-1-related variables. Moreover, a significant relationship between calcaneal quantitative ultrasound index/stiffness and femoral/lumbar BMD values from DXA was described. The multivariate analysis showed an independent association between calcaneal quantitative ultrasound index/stiffness and body mass index, higher CD4+ T-cell numbers and low 25-OH D2/D3 vitamin D levels <10 ng/mL (P-values: 0.004, 0.016, and 0.015, respectively).ConclusionAs an alternative and/or integrative examination to DXA, calcaneal QUS could be proposed as a useful screening in HIV-1-infected patients for assessing bone health impairment. In fact, the results obtained confirm that calcaneal QUS may be useful for monitoring bone status, being a noninvasive and inexpensive technique, especially in those subjects with the classical traditional risk factors for bone damage that were observed earlier in HIV-1 population.

Low Serum Vitamin D: A Surrogate Marker for Advanced Colon Adenoma?

To examine the association between low 25-OH Vitamin D levels and prevalence of advanced adenomas (AAs) in screening/surveillance colonoscopy patients. Low serum 25-OH Vitamin D has been associated with an increased risk for colon cancer. In the Adenoma-Carcinoma pathway, a subset of colon polyps (AA) have been regarded as high-risk precursor lesions. We used a retrospective case-control design to examine the association between Vitamin D deficiency and the prevalence of AA in a high-risk population. We examined a total of 354 patients who presented for initial screening or surveillance colonoscopy at our Colon Cancer Prevention Program. Our main exposure variable was serum Vitamin D levels and the outcome was AAs defined as those adenomas that were large (≥1 cm) or had advanced pathology (>25% villous components or high-grade dysplasia). Known risk factors were also collected from the patients' charts including gender, age, smoking, and family history. Bivariate and multivariate analyses were performed to examine the relationship between serum 25-OH Vitamin D levels and AAs. A total of 354 patients [(males, 188; females, 166); average age, 61 y] charts were reviewed. Vitamin D levels ranged between 4 and 70 ng/mL, with a mean of 25 ng/mL (clinical laboratory normal>30 ng/mL). There was no significant association between serum levels and time of the year of blood draw. Risk for tubular adenoma and AA increased as Vitamin D levels decreased to <30 ng/mL (P=0.002). In total, 80% of AAs were detected in patients whose levels were below this value (odds ratio, 3.36; 95% confidence interval, 1.40-8.03; P=0.007). Bivariate analysis also showed a positive association between smokers with AA as well as those with a family history of colon cancer (P=0.011) and low Vitamin D levels (P=0.001). A multivariate analysis using quintiles of Vitamin D levels demonstrated an increased risk of AAs for patients with levels in the second quintile (33 ng/mL) (odds ratio, 4.3; P=0.01) MAIN CONCLUSIONS:: Most patients presenting in our Colon Cancer Prevention Program have low levels of serum 25-OH Vitamin D. Analysis of the results of both screening and surveillance colonoscopies demonstrated an inverse relation between serum 25-OH Vitamin D level and AAs.

Correlation between disease activity of pediatric-onset systemic lupus erythematosus and level of vitamin D in Taiwan: A case-cohort study.

Vitamin D deficiency has been associated with systemic lupus erythematosus (SLE), but there is no consensus on the role of serum vitamin D in evaluating or predicting disease activity. This study aimed to demonstrate the direct correlation between vitamin D level and pediatric-onset SLE disease activity by a retrospective cohort study design. Thirty-five patients with pediatric-onset SLE and paired sera at the active and inactive disease states were enrolled. Disease activity was defined by Systemic Lupus Erythematosus Disease Activity Index 2000, and active lupus nephritis (LN) was defined as active urine sediment, and proteinuria >2+on stick or >500mg/day. All data were reviewed and calculated from previous medical records. The levels of both vitamin D2 and vitamin D3 were checked by electrochemiluminescence immunoassay. Serum 25-hydroxyvitamin D (25-OH D) levels in the active status were significantly lower compared to that in inactive disease status (12.0±7.2ng/mL vs. 15.4±7.4ng/mL, p=0.005). A subgroup analysis revealed that at active disease status, patients with LN had lower 25-OH D levels than patients without LN (16.3±8.2ng/mL vs. 9.8±5.6ng/mL, p=0.023). Moreover, there is a significant inverse correlation between serum 25-OH D levels and Systemic Lupus Erythematosus Disease Activity Index 2000 at both inactive (r=-0.335, p=0.003) and active (r=-0.373, p=0.016) disease status. Serum vitamin D levels are inversely correlated with SLE disease activity at both active and inactive disease status, and also with the presence of LN at active disease stage.

Low 25-OH vitamin D levels at time of diagnosis and recurrence of ovarian cancer.

The objective of this study was to evaluate the correlation between 25-OH vitamin D and ovarian cancer as a diagnostic marker or recurrence disease marker. We studied the following: (1) 61 women without gynecologic diseases, (2) 45 women affected by benign ovarian disease, (3) 46 women with recent diagnosis of ovarian cancer, (4) 26 follow-up women with recurrent ovarian cancer, and (5) 32 follow-up women with stable ovarian cancer. The 25-OH vitamin D was quantified with LUMIPULSE® G 25-OH vitamin D on LUMIPULSE® G 1200 (Fujirebio, Japan). As a threshold value, identified by ROC curve analysis, 20.2ng/mL (sensitivity 73.3%, specificity 84%) was chosen corresponding to the limit between sufficient and insufficient 25-OH vitamin D according to the WHO. Low 25-OH vitamin D levels were observed in 26% of women without gynecologic diseases, in 80% of women with recent diagnosis of ovarian cancer and in 24% women affected by benign ovarian diseases (p < 0.001). The follow-up study showed an insufficient level of 25-OH vitamin D in 73% women with recurrent ovarian cancer and in 47% women with stable ovarian cancer (p < 0.0003). This study showed that patients with ovarian cancer are often insufficient in 25-OH vitamin D compared to women with benign ovarian diseases. The women with recurrent ovarian cancer presented more often low levels compared to women with stable ovarian cancer. This study suggests that 25-OH vitamin D, due to its antiproliferative properties, can be a good marker for ovarian cancer also.

Low 25-OH vitamin D levels are not associated with coronary artery calcium or obstructive stenoses.

It is unclear whether low vitamin D is a significant risk factor for the presence of either calcific atherosclerosis or obstructive coronary artery stenoses. In this study, we measured the 25-OH vitamin D levels of 1131 consecutive individuals who underwent coronary artery calcium (CAC) scoring and coronary computed tomographic angiography at our institution. We looked for any association of 25-OH vitamin D levels with CAC scores. We also studied the relation of 25-OH vitamin D levels with the presence of 70% or more obstructive coronary artery stenoses, found initially by coronary computed tomographic angiography and confirmed subsequently by invasive angiography. There were 132 (11.7%) 25-OH vitamin D deficient (<20 ng/ml) and 295 (26.1%) 25-OH vitamin D insufficient (21-29 ng/ml) individuals in this study. There was no detectable association between 25-OH vitamin D levels and CAC scores. The median (interquartile range) CAC score of 25-OH vitamin D deficient, insufficient, and adequate patients was 451 (80-1083), 338 (52-830), and 450 (100-1062), respectively. Also, no relation was noted between 25-OH vitamin D levels and the presence of severely obstructive coronary artery disease. The frequency of severe coronary artery disease in 25-OH vitamin D deficient, insufficient, and adequate patients was 3.8, 2.0, and 4.0%, respectively. Low 25-OH vitamin D levels were not associated with CAC or severely obstructive stenoses.

Fractures Related to Metabolic Bone Disease in Children with Congenital Heart Disease.

Critically ill children with congenital heart disease (CHD) are at risk for metabolic bone disease (MBD) and bone fractures. Our objective was to characterize a cohort of CHD patients with fractures and describe a Fragile Bone Protocol (FBP) developed to reduce fractures. Patients who developed fractures in the Cardiac Intensive Care Unit (CICU) of Boston Children's Hospital from 3/2008 to 6/2014 were identified via quality improvement and radiology databases. The FBP (initiated July 2011) systematically identifies patients at risk for MBD and prescribes special handling precautions. Twenty-three fractures were identified in 15 children. Median age at fracture identification was 6.2 months, with a median duration of hospitalization before fracture diagnosis of 2.7 months. Six patients (40%) had single ventricle CHD. Hyperparathyroidism and low 25-OH vitamin D levels were present in 77% and 40% of those tested, respectively. Compared with patients not diagnosed with fractures, fracture patients had increased exposure to possible risk factors for MBD and had elevated parathyroid and decreased calcitriol levels.Six patients (40%) did not survive to hospital discharge, compared with an overall CICU mortality rate of 2.6% (P < .01). The fracture case rate before implementation of the FBP was 2.6 cases/1000 admissions and was 0.7/1000 after implementation of the FBP (P = .04). Critically ill CHD patients are at risk for fractures. They represent a complex group who frequently has hyperparathyroidism and decreased calcitriol levels, and each may predispose to fractures. FBPs consisting of identification and careful patient handling should be considered in at-risk patients.

Bone and Spinal Muscular Atrophy

Spinal Muscular Atrophy (SMA) is an autosomal recessive neuromuscular disease, leading to progressive denervation atrophy in the involved skeletal muscles. Bone status has been poorly studied. We assessed bone metabolism, bone mineral density (BMD) and fractures in 30 children (age range 15–171months) affected by SMA types 2 and 3.Eighteen children (60%) had higher than normal levels of CTx (bone resorption marker); 25-OH vitamin D was in the lower range of normal (below 20ng/ml in 9 children and below 12ng/ml in 2). Lumbar spine BMAD (bone mineral apparent density) Z-score was below −1.5 in 50% of children. According to clinical records, four children had sustained four peripheral fractures; on spine X-rays, we observed 9 previously undiagnosed vertebral fractures in 7 children. There was a significant inverse regression between PTH and 25-OH D levels, and a significant regression between BMC and BMAD values and the scores of motor-functional tests.Even if this study could not establish the pathogenesis of bone derangements in SMA, its main findings – reduced bone density, low 25OH vitamin D levels, increased bone resorption markers and asymptomatic vertebral fractures also in very young patients – strongly suggest that even young subjects affected by SMA should be considered at risk of osteopenia and even osteoporosis and fractures.

MP71-01 SERUM VITAMIN D LEVELS AND PROSTATE VOLUME

You have accessJournal of UrologyBenign Prostatic Hyperplasia: Evaluation and Symptoms1 Apr 2015MP71-01 SERUM VITAMIN D LEVELS AND PROSTATE VOLUME Yaw Nyame, Richard Kalu, Ganesh Kartha, Tyler Maiers, Diana Bowen, Rick Kittles, and Adam Murphy Yaw NyameYaw Nyame More articles by this author , Richard KaluRichard Kalu More articles by this author , Ganesh KarthaGanesh Kartha More articles by this author , Tyler MaiersTyler Maiers More articles by this author , Diana BowenDiana Bowen More articles by this author , Rick KittlesRick Kittles More articles by this author , and Adam MurphyAdam Murphy More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.2614AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Studies suggest that vitamin D decreases prostate proliferation and is associated with prostate cancer (PCa) progression. We hypothesize that serum 25-hydroxyvitamin D (25-OH D) is anti-proliferative in the benign and malignant prostate. We investigate the association between serum 25-OH D levels and prostate volume, serum PSA, and PSA density (PSAD). METHODS This cross-sectional study is nested from a large case-control study assessing biological and environmental mediators of 25-OH D and prostate cancer (PCa) among 40-79 year old ambulatory, unrelated men, prospectively enrolled in academic, outpatient urology clinics in Chicago, IL. Clinical and demographic data were collected by self-administered questionnaires and chart review. Peripheral blood was collected for serum 25-OH D at the time of transrectal ultrasound (TRUS) guided prostate biopsy for elevated PSA or abnormal digital rectal examination. Prostate volume was estimated by the ellipsoid formula during TRUS. PSAD was calculated as the serum PSA (ng/ml) that prompted the prostate biopsy divided by the estimated prostate volume (g). Univariate analysis of variance was performed to evaluate the association of prostate volume, PSA, and PSAD with various 25-OH D clinical cut points using t-tests. Best-fit linear regressions were constructed controlling for age, PSA, 5-alpha reductase inhibitor use, race, season of blood draw, and alcohol and tobacco use. RESULTS Our analysis included 595 men. The median age was 62.8 years for PCa cases and 61.5 years for the negative biopsies (p = 0.02). Serum 25-OH D was inversely correlated with prostate volume for all the clinical cut points (Table 1). This association was statistically significant for 25-OH D levels < 16 ng/mL (p = 0.02) and < 20 ng/mL (p < 0.001). Serum PSA level was significantly higher in men with lower 25-OH D levels at all cut points. PSAD was not significantly associated with 25-OH D, (all p > 0.20). On linear regression, 25-OH D inversely correlated with prostate volume (β = -0.40, SE = 0.11, p < 0.001). CONCLUSIONS Vitamin D is inversely correlated with prostate volume and is likely independent of PSA given the non-significant relationship with PSA density. Vitamin D may be a chemopreventive agent for BPH/LUTS and PCa, and warrants further investigation. Relationship of prostate volume, PSA and PSA density to Vitamin D levels (N = 595) Category 25-OH D < 12 ng/mL 25-OH D ≥ 12 ng/mL p-value 25-OH D < 16 ng/mL 25-OH D ≥ 16 ng/mL p-value 25-OH D < 20 ng/mL 25-OH D ≥ 20 ng/mL p-value Prostate volume, g 49.9 (27.2) 46.1 (27.2) 0.22 50.7 (27.8) 45.1 (26.8) 0.02 51.2 (31.8) 43.6 (23.0) < 0.001 Serum PSA, ng/mL 11.5 (11.4) 8.5 (10.1) 0.02 12.2 (12.8) 8.2 (8.9) < 0.001 11.4 (12.0) 7.9 (8.7) < 0.001 PSA Density (ng/mL/g) 0.28 (0.2) 0.24 (0.3) 0.27 0.28 (0.2) 0.23 (0.3) 0.09 0.27 (0.2) 0.23 (0.3) 0.10 Mean (SD) are reported for prostate volume, PSA, and PSAD for each of the above cutpoints © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e911 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Yaw Nyame More articles by this author Richard Kalu More articles by this author Ganesh Kartha More articles by this author Tyler Maiers More articles by this author Diana Bowen More articles by this author Rick Kittles More articles by this author Adam Murphy More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Childhood 25-OH Vitamin D Levels and Carotid Intima-Media Thickness in Adulthood: The Cardiovascular Risk in Young Finns Study

Low vitamin D levels in adulthood have been associated with cardiovascular disease. To investigate if low vitamin D levels in childhood are related with increased carotid artery intima-media thickness (IMT) in adulthood. The analyses included 2148 subjects from the Cardiovascular Risk in Young Finns Study, aged 3-18 years at baseline (in 1980). Subjects were re-examined at age 30-45 years (in 2007). Childhood levels of 25-hydroxy-vitamin D were measured from stored serum in 2010. The carotid artery IMT from 2007 was used. When adjusted for age, sex, and childhood risk factors, continuous data of childhood 25-OH vitamin was inversely associated with adulthood carotid IMT levels among females (β ± SE -0.006 ± 0.003, P = 0.03), but not among males (0.001 ± 0.004, P = 0.88). Children with 25-OH vitamin D levels in the lowest quartile (<40 nmol/L) had significantly increased odds of having high-risk IMT (highest decile of common carotid or carotid bulb IMT or carotid plaque) as adults, in analyses adjusted for age, sex and either childhood risk factors (odds ratio 1.70 [95 % CI 1.15-2.31], P = 0.0007) or adult risk factors, including adult vitamin D levels (odds ratio 1.80 [1.30-2.48], P = 0.0004). In sex-specific analyses, these associations were significant both in females and males (P always <0.05). In sensitivity analyses, those with childhood vitamin D levels in the lowest quintile (<37 nmol/L), gave similar results to those using a quartile cut-point. Low 25-OH vitamin D levels in childhood were associated with increased carotid IMT in adulthood.