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Fri, 22.11.24

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September 2015
Inbal Mayan MD, Raz Somech MD PhD, Atar Lev MSc, Avner H. Cohen, Naama W. Constantini MD and Gal Dubnov-Raz MD MSc

Background: Several studies have identified associations between low vitamin D concentrations and risk of upper respiratory infections (URI). T lymphocytes have a major anti-viral role, are affected by vitamin D metabolism, and may mediate the link between vitamin D and URIs. Competitive swimmers have a relatively high rate of URIs, alongside a high prevalence of low vitamin D concentration. 

Objectives: To examine the associations linking T cell receptor excision circles (TREC, markers of thymus activity), circulating 25(OH)D concentrations and the effect of vitamin D supplementation, and URI symptoms in young competitive swimmers.

Methods: We tested 82 adolescent swimmers for serum 25(OH)D and TREC concentrations and found that 55 had vitamin D insufficiency. Randomized supplementation of either vitamin D3 or placebo was given for 12 winter weeks. URI symptoms were recorded weekly. The associations between TREC copy numbers, vitamin D and URI burden were examined.

Results: TREC concentrations decreased with the participants’ age (r = -0.346, P = 0.003), with no significant between-gender difference. TREC concentrations did not materially differ among subjects with normal, insufficient or deficient vitamin D status, and were not affected by vitamin D supplementation. No significant correlations were found between TREC levels or their changes during the study period, and mean URI severity or duration. 

Conclusions: Thymus activity, represented by higher TREC levels, was not related to vitamin D concentrations or status, and was not affected by vitamin D supplementation in adolescent swimmers. TREC concentrations were not associated with URI severity or duration in this population.

 

February 2015
Narin N. Carmel MD, Pnina Rotman-Pikielny MD, Alexey Lavrov MD and Yair Levy MD


Background: Vitamin D is a pivotal factor in calcium homeostasis and exerts immunomodulatory effects. Hypovitamin D has been demonstrated in systemic sclerosis (SSc) patients and may be related to more severe disease of longer duration and with extensive skin involvement. 

Objectives: To seek anti-vitamin D antibodies in SSc patients, as found by previous research in patients with systemic lupus erythematosus (SLE).

Methods: The study included 54 SSc patients and 41 volunteers. Immunoglobulin (Ig) G and IgM autoantibody levels against 25(OH)D and 1,25(OH)D were obtained from patients and controls and compared. SSc patients were assessed for autoantibody profile and disease severity. 

Results: Vitamin D antibodies were present in 87% of SSc patients and 42% of controls. Higher levels of anti-25(OH)D IgM antibodies were detected in SSc patients compared to controls (0.48 ± 0.22 vs. 0.29 ± 0.29, respectively, P = 0.002); however, IgG levels were lower in the SSc patients. No such discriminative effect was found regarding anti-1,25(OH)D antibodies between SSc and controls. No correlation was found between vitamin D antibodies and other autoantibodies, disease severity, or target organ damage.

Conclusions: To the best of our knowledge, this is the first study of these novel anti-vitamin D antibodies in SSc patients and the first time a correlation between IgM 25(OH) vitamin D antibodies and scleroderma has been identified. Further research on the pathophysiological significance and therapeutic potential of vitamin D is required. 

 
June 2014
Mahmud Mahamid MD, Omar Abu-Elhija MD, Mosab Samamra MD, Ammad Mahamid MD and William NseirMD

Background: Alopecia areata (AA) is an autoimmune disease, based on the response to local and/or systemic corticosteroid treatment. The role of vitamin D in the pathogenesis of immune/autoimmune mediated diseases has been widely investigated.

Objectives: To investigate a possible association between serum 25-hydroxyvitamin D levels and alopecia areata.

Methods: The study included 23 patients diagnosed with AA followed at our outpatient clinic during the period March 2010 to May 2011, as well as a control group matched for age and gender. All subjects underwent a complete work-up and medical examination, anthropometric measurements and laboratory tests. Laboratory tests included complete blood count, C-reactive protein (CRP), and vitamin D levels.

Results: Mean CRP values were significantly higher in the AA group than the control group (1.1 ± 0.7 mg/dl vs. 0.4 ± 0.8 mg/dl, P < 0.05). Vitamin D levels were significantly decreased in the AA group (11.32 ± 10.18 ng/ml vs. 21.55 ± 13.62 ng/ml in the control group, P < 0.05). Multivariate analysis showed that CRP (odds ratio 3.1, 95% confidence interval 2.6–4.2, P = 0.04) and serum vitamin D levels < 30 ng/ml (OR 2.3, 95%CI 2.2–3.1, P = 0.02) were associated with AA. 

Conclusions: We found a significant correlation between AA and vitamin D deficiency. Vitamin D deficiency can be significant risk factor for AA occurrence.

January 2014
Alon Eisen, Eli Lev, Zaza Iakobishvilli, Avital Porter, David Brosh, David Hasdai and Aviv Mager
Background: Treatment with HMG-CoA reductase inhibitors (statins) is often complicated by muscle-related adverse effects (MAEs). Studies of the association between low plasma vitamin D levels and MAEs have yielded conflicting results.

Objectives: To determine if low plasma vitamin D level is a risk factor for MAEs in statin users.

Methods: Plasma levels of 25(OH) vitamin D were measured as part of the routine evaluation of unselected statin-treated patients attending the coronary and lipid clinics at our hospital during the period 2007–2010. Medical data on muscle complaints and statin use were retrieved from the medical files. Creatine kinase (CK) levels were derived from the hospital laboratory database.

Results: The sample included 272 patients (141 men) aged 33–89 years. Mean vitamin D level was 48.04 nmol/L. Levels were higher in men (51.0 ± 20.5 vs. 44.7 ± 18.9 nmol/L, P = 0.001) and were unaffected by age. MAEs were observed in 106 patients (39%): myalgia in 95 (35%) and CK elevation in 20 (7%); 11 patients (4%) had both. There was no difference in plasma vitamin D levels between patients with and without myalgia (46.3 ± 17.7 vs. 48.9 ± 21.0 nmol/L, P = 0.31), with and without CK elevation (50.2 ± 14.6 vs. 47.8 ± 20.3 nmol/L, P = 0.60), or with or without any MAE (50.4 ± 15.0 vs. 47.8 ± 10.2 nmol/L, P = 0.27). These findings were consistent when analyzed by patient gender and presence/absence of coronary artery disease, and when using a lower vitamin D cutoff (< 25 nmol/L).

Conclusions: There is apparently no relationship between plasma vitamin D level and risk of MAEs in statin users.

November 2013
O. Havakuk, M. Entin-Meer, J. Ben-Shoshan, P. Goryainov, S. Maysel-Auslender, E.l Joffe and G. Keren
 Background: Vitamin D has been shown to induce beneficial effects on cardiovascular and renal morbidity by regulating inflammation and tissue fibrosis.

Objectives: To evaluate the effect of vitamin D analogues on cardiac function and fibrosis in an animal model of cardiorenal syndrome.

Methods: Unilateral nephrectomy was performed and myocardial infarction induced in rats. Rats were treated with vitamin D receptor activator (VDRA, paricalcitol, 40 ng/250 g x 3/week) versus a vehicle. A third group of animals, which served as the control, underwent sham surgery and received no treatment. After 4 weeks of treatment, cardiac function and fibrosis were assessed by trans-thoracic echo and histology, respectively. As a parameter of systemic inflammation, previously shown to be altered in acute coronary syndrome, T regulatory (Treg) cell levels were measured by flow cytometry. Renal dysfunction was documented by standard laboratory tests.

Results: After 4 weeks of treatment, no significant improvement in cardiac function parameters was noted following VDRA administration. VDRA treatment did not significantly alter Treg cell systemic levels. Consistently, despite a trend toward less extent of myocardial fibrosis, we found no clear beneficial effects of VDRA on myocardial tissue inflammation and remodeling.

Conclusions: Vitamin D treatment showed no beneficial effects on cardiac function parameters and fibrosis in an animal model of cardiorenal syndrome. 

October 2013
O. Eyal, M. Aharon, R. Safadi and M. Dranitzki-Elhalel
 Background: Vitamin D deficiency was shown to be prevalent among renal transplant recipients in northern countries, but little is known regarding risk factors.

Objectives: To test vitamin D levels in kidney transplant recipients residing closer to the equator, compare them to levels in liver transplant recipients and hemodialysis patients, and identify possible risk factors.

Methods: In a cross-sectional study 103 kidney transplant recipients, 27 liver transplant recipients and 50 hemodialysis patients followed at our institute were tested for vitamin D levels. Demographic data, medical history and current treatment were recorded from the medical files.

Results: Inadequate vitamin D levels (< 30 ng/ml) were found in 75% of all patients and 75% of all kidney transplant recipients. Vitamin D levels were higher among dialysis patients than transplant recipients, though deficiency rates were similar. No association was found between kidney function and vitamin deficiency. Deficiency was associated with higher prednisone doses, use of mycophenolate sodium, tacrolimus, and iron supplements, or lower doses of vitamin D supplementation.

Conclusions: Despite potential higher ultraviolet B exposure, inadequate vitamin D levels were prevalent in our study group. Importantly, some immunosuppressive medications were associated with vitamin D deficiency and high doses of vitamin D were associated with less deficiency.

R. Blecher, Z. Wasrbrout, Y. Arama, R. Kardosh, G. Agar and Y. Mirovsky
 Background: Osteoporosis is considered the most common bone disease in humans and the most common cause of fractures.

Objectives: To identify possible risk factors associated with a decreased level of care for osteoporosis among patients presenting acutely with the major types of fragility fractures, but also among patients who remain undertreated following their discharge.

Methods: We conducted a retrospective questionnaire-based cohort study. We searched our databases for patients admitted acutely with proximal humerus, distal forearm, thoracolumbar spine, and proximal femur fractures. A questionnaire was used to evaluate osteoporotic care including a referral to DEXA and any associated prescribed medication.

Results: The study group included 114 patients or their caregivers. The osteoporosis care rate rose from 56.1% (n=64) before admission to 71% (n=81) at follow-up. Significant risk factors associated with a decreased care rate prior to admission were the presence of fewer than three comorbidities, and a combination of male gender and young age. Continued neglect at follow-up was associated with the opposite risk factors, such as older age, multiple comorbidities, and polypharmacy. An additional finding was that treated patients had a significantly increased likelihood of presenting with vertebral fractures.

Conclusions: While the association of osteoporosis with the elderly may decrease its screening rates among younger and healthier patients, fragility fractures may be viewed as “end-stage” bone disease, rendering osteoporotic care inefficient.

 

July 2013
G. Korchia, Y. Amitai, G. Moshe, L. Korchia, A. Tenenbaum, J. Rosenblum and A. Schechter

Background: Hypovitaminosis D is common worldwide, even in sunny regions.

Objectives: To assess the prevalence and determinants of vitamin D deficiency in toddlers.

Methods: A cross-sectional prospective study was conducted in healthy Jewish children aged 1.5–6 years at five primary care pediatric clinics in the Jerusalem area during the period October 2009 to November 2010. Parents were interviewed regarding personal and demographic data and sun exposure. Blood samples were obtained for serum 25-hydroxyvitamin D [25-OHD] level. Vitamin D deficiency and insufficiency were defined as 25-OHD < 20 ng/ml and < 30 ng/ml, respectively.

Results: Of 247 children studied, 188 (76%) were ultra-Orthodox and 59 (24%) were Orthodox, traditional or secular. Mean (± SD) 25-OHD level was 25.7 ± 10 ng/ml. Only 73 children (29.6%) had sufficient 25-OHD levels, 104 (42.1%) had insufficiency, and 70 (28.3%) had 25-OHD deficiency. The difference between ultra-Orthodox and others was insignificant (25 ± 10 vs. 27.8 ± 10.5 ng/ml respectively, P = 0.062). Children aged 1.5–3 years had higher 25-OHD levels than those aged 3–6 years (28.6 ± 10.7 and 24 ± 9.2 ng/ml respectively, P < 0.001). Vitamin D deficiency was more common in winter (53%) and autumn (36%) than in summer (19%) and spring (16%). Toddlers attending long-day kindergartens had higher 25-OHD level than those staying at home or at short-day kindergartens (28.8 ± 11.5 and 24.7 ± 9.6 ng/ml respectively, P < 0.05).

Conclusions: A high prevalence of vitamin D deficiency was found in toddlers in our study, mainly in older children and in the winter and autumn. We recommend routine supplementation of vitamin D for children beyond the agear.

October 2012
E. Segal, S. Felder , N. Haim, H. Yoffe-Sheinman, A. Peer, M. Wollner, Z. Shen-Or and S. Ish-Shalom

 Background: Vitamin D status is not evaluated routinely in cancer patients with bone metastasis who are treated with bisphosphonates.

Objectives: To assess the effect of vitamin D status on risk of hypocalcemia and quality of life in these patients.

Methods: We performed laboratory tests for routine serum biochemistry, 25(OH)D, plasma parathyroid hormone (PTH) and bone turnover markers (CTX, P1NP) in 54 patients aged 57.5 ± 13 years treated with intravenous bisphosphonates.

Results: Most of the patients (n=44, 77.8%) did not receive calcium and vitamin D supplementation. Their mean serum 25(OH)D levels (12.83 ± 6.86 ng/ml) correlated with vitamin D daily intake (P = 0.002). In 53 patients (98.1%) 25(OH)D levels were suboptimal (< 30 ng/ml). Albumin-corrected calcium levels correlated with plasma PTH (P = 0.001). No correlation was observed between daily calcium intake and serum calcium (P = 0.45). Hypocalcemia was observed in one patient. Mean plasma PTH was 88.5 ± 65 ng/L. Plasma PTH correlated negatively with 25(OH)D serum levels (P = 0.003) and positively with P1NP (P = 0.004). Albumin-corrected calcium correlated negatively with P1NP (mean 126.9 ± 191 ng/ml) but not with CTX levels (mean 0.265 ± 0.1 ng/ml) (P < 0.001). There was no correlation among quality of life parameters, yearly sun exposure and 25(OH)D levels (P = 0.99).

Conclusions: Vitamin D deficiency is frequent in oncology patients with bone metastasis treated with bisphosphonates and might increase bone damage. Our results indicate a minor risk for the development of severe hypocalcemia in vitamin D-deficient patients receiving bisphosphonate therapy. Although vitamin D deficiency might have some effect on the quality of life in these patients, it was not proven significant.
 

February 2012
D. Itzhaky, D. Amital, K. Gorden, A. Bogomolni, Y. Arnson and H. Amital

Background: Vitamin D is increasingly associated with the pathology of cognition and mental illness. Vitamin D receptors have been detected on neurons that regulate behavior.

Objective: To assess vitamin D serum concentrations in patients with major depression and schizophrenia as compared to healthy controls and to determine if a correlation exists between serum levels of vitamin D and disease activity.  

Methods: We recruited 50 patients with schizophrenia and compared them to 33 patients with major depression and 50 controls with no major psychopathology. The Positive and Negative Syndrome Scale (PANSS) for schizophrenia and the Hamilton Depression scale for depression were administered on the same day the blood samples were drawn. We used LIAISON® 25-OH vitamin D (DiaSorin) immunoassay to measure serum concentrations of 25-OH vitamin D.

Results: Lower serum vitamin D concentrations were detected among patients with schizophrenia (15.0 ± 7.3 ng/ml) compared to patients with depression (19.6 ± 8.3 ng/ml) and to controls (20.2 ± 7.8 ng/ml, P < 0.05). We found no correlation between disease activity, measured by the PANSS score, and vitamin D levels.   

Conclusions: Serum vitamin D levels were lower in patients with schizophrenia as compared to patients with depression and to healthy controls. No correlation was found between serum concentration and disease activity. Additional studies are needed to elucidate the role of vitamin D in the autoimmune mechanism and in the pathogenesis of schizophrenia.

April 2011
M. Harari, E. Dramsdahl, S. Shany, Y. Baumfeld, A. Ingber, V. Novack and S. Sukenik

Background: Ultraviolet B (UVB) rays are required by the skin for the production of vitamin D. The intensity of UVB at the Dead Sea area is the lowest in the world. Low vitamin D levels are often associated with musculoskeletal symptoms.

Objectives: To assess the effectiveness of climatotherapy at the Dead Sea on the production of vitamin D in Norwegian patients suffering from various rheumatic diseases and to investigate possible associations between increased vitamin D serum levels, musculoskeletal symptoms and disease severity.

Methods: Sixty Norwegian patients who came to the Dead Sea area for 21 days of medical rehabilitation were divided into three groups according to their diagnosis: chronic pain syndromes, i.e., low back pain or fibromyalgia (Group 1, n=33); rheumatoid arthritis (Group 2, n=16); and osteoarthritis (Group 3, n=11). Serum 25-hydroxyvitamin D (25-OH-D) levels were determined at arrival and prior to departure. The treatment protocol included daily sun exposure (climatotherapy), bathing in the Dead Sea and mineral spring water (balneotherapy), mud applications and fitness classes.

Results: 25-OH-D serum levels increased significantly from 71.3 ± 26.6 nM at arrival to 89.3 ± 23.2 nM prior to departure (P < 0.001). Adjusted for the initial levels of pain (assessed by a visual analog scale) and disease severity, a direct correlation was observed between increased 25-OH-D serum levels and pain reduction (P = 0.012) and reduction of disease severity (P = 0.02).

Conclusions: Climatotherapy at the Dead Sea induces significant changes in vitamin D. Increased 25-OH-D serum levels are associated with reduced musculoskeletal pain and disease severity.
 

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