Ca&Bone

[Vitamin D in autoimmun disorders: the immunregulatory effect of vitamin D and therapeutic opportunities]

ZÖLD Éva, SZODORAY Péter, GAÁL János, SZEGEDI Andrea, SZEGEDI Gyula, BODOLAY Edit

DECEMBER 28, 2009

Ca&Bone - 2009;12(03)

[There is recent evidence that genetic and environmental factors play an important role in the development of autoimmune diseases. Vitamin D deficiency is one of the environmental factors that may play a role in developing autoimmune diseases. Low vitamin D status has been implicated in the etiology of autoimmune diseases such as multiple sclerosis, systemic lupus erythematosus, rheumatoid arthritis, inzulin dependent diabetes mellitus, and inflammatory bowel disease. Experimentally, vitamin D deficiency results in an increased incidence of autoimmune disease. The authors discuss the accumulating evidence pointing to a link between vitamin D and autoimmunity. The optimal level of vitamin D intake is necessary to normalize the immune functions and it plays an important role in the development of self-tolerance. Targets for vitamin D in the immune system have been identified and the mechanism of vitamin D mediated immunoregulation is beginning to be understood. On the basic of recent knowledge, vitamin D causes a decrease in Th1-driven autoimmune response and repairs the function of regulatory T cells. Increased vitamin D intakes might decrease the incidence and severity of autoimmune diseases.]

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[Overcome of bisphosphonate resistance with alphacalcidol: results of a one year, open follow-up study]

GAÁL János, BENDER Tamás, VARGA József, HORVÁTH Irén, KISS Judit, SOMOGYI Péter, SURÁNYI Péter

[INTRODUCTION - A considerable part of osteoporotic patients do not respond satisfactorily to adequate treatment with a bisphosphonate plus supplementation with calcium and conventional vitamin D3. This study intended to determine whether the replacement of vitamin D3 with alphacalcidol results in any BMD increase, i.e. is it possible to overcome resistance to bisphosphonates. PATIENTS AND METHOD - In 76 patients unresponsive to the combination of alendronate and conventional vitamin D3, the latter had been replaced with alphacalcidol (0.5 μg/day), and then the patients were followed up for a year. Clinical and laboratory parameters were recorded at baseline and after one year of treatment; and their changes were analysed by statistical methods. RESULTS - After treatment for one year, Wilcoxon test revealed a small but statistically significant (p<0.001) increase in the BMD values of the forearm (+2.2%) and lumbar vertebrae (+1.4%). At the end of the treatment period, the following, significant changes were observed compared to baseline (median values): serum calcium level increased by 0,06 mmol/l; serum phosphorus level decreased by 0.05 mmol/l, serum alkaline phosphatase activity decreased by 13 U/l, and urinary calcium/creatinine ratio in first-voided morning urine increased by 0.1. Additionally, serum PTH level decreased by 10.7 pg/ml (median). Serum levels of osteocalcin decreased by 0.4 ng/ml, along with the urinary D-Pyr /kreatinine ratio by 0.2 nmol/mmol (median). No significant increase of adverse events occurred. DISCUSSION - As suggested by our results, combination therapy with alendronate and alfacalcidol increases bone density and improves the biochemical markers of bone turnover - without any substantial increase in the incidence of adverse effects.]

Ca&Bone

[Hip fractures in Hungary between 2001 and 2008 - Assessment of the beneficial effect of bisphosphonates on the risk of hip fractures on the basis of Hungarian data]

HÉJJ Gábor

[The overall prevalence of osteoporosis in developed countries is estimated to be 9-15%. Mortality in the first year after the fracture is 15-20%, and half of the survivors remain partly or fully dependent on others’ support. Owing to the increasing life expectance and the diseases of civilisation, the incidence of osteoporotic fractures is expected to double in the next thirty years. The network of centers that has been developed since 1995 under the National Osteoporosis Program and the accreditation system of the National Osteoporosis Center provided up-to-date education of the physicians (densitometry assistants) who work within the network. The diagnostic restrictions followed by the reduction of support to 70% since 2006 fall resulted in a dramatic reduction in the number of treated patients.]

Ca&Bone

[Modelling of burden of femoral neck fracture from purchaser’s point of view]

SEBESTYÉN Andor, PÉNTEK Márta, GULÁCSI László, NYÁRÁDY József

[OBJECTIVE - This study provides a model of the treatment cost of femoral neck fracture and financial burden of the annual fracture cases at 2009 financial level from health insurance point of view. METHOD - The costs of the treatment of femoral neck fractures are modelled according to the actually OEP reimbursed types of care including acute inpatient care, chronic inpatient care, outpatient care, pharmaceuticals and medical devices, home care (nursing), cost of travelling or transport and the disability to work. Cases healing following primary treatment (without complications) and cases with complications are examined separately. The costs of most common complications with large surgical operation are calculated. RESULTS - The cost of patients in active age-groups cured by primary treatment can vary in a range of 1.010.110- 1.479.034 HUF depending on cost level of individual care and utilization, while the cost of patients in retired agegroups (pensioners) can vary in a range 635.350- 1.104.274 HUF. The cost of patients with complication (primary treatment and complication) in active agegroups can reach. 1 858.438-3.133.096 HUF depending on cost level of individual care and utilization, while the cost of patients in retired age-groups (pensioners) can reach 1.108.918-2.383.576 HUF. According to our model calculations, the cost of primary treatment of femoral neck fractures and essential further treatment represents an annual burden of 4.373.857.668-6.247.717.438 HUF for the health insurance system. CONCLUSION - In order to reduce the incidence of hip fractures one should emphasize the importance of current and future interventions, which projects the possibility of reducing the financial burden at societal level. The analysis of financial burden could serve as a base for health-economics studies, by elaborating a cost-effective strategy supported by professional and political decision makers.]

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[VITAMIN D TREATMENT: HORMONE THERAPY FOR PATIENTS WHO NEED IT OR SIMPLY A SUPPLEMENTATION FOR EVERYONE?]

SPEER Gábor

[Various medical associations issue different recommendations for the prevention and treatment of vitamin D deficiency. These significant differences are partly explained by the different definition of normal vitamin D level and the use of completely different mathematical models to predict the increase in vitamin D level as a response to therapy. According to the Institute of Medicine (IOM), the target vitamin D level is 20 ng/ml, whereas the Endocrine Society (ES) recommends 30 ng/m as the miminum target value. According to the ES, a 1 ng/ml increase of vitamin D level can be reached by a daily intake of 100 NE, while the IOM recommends 3.6 ng/ml. Moreover, the IOM states that the effect of therapy on serum level is nonlinear. These differences show that the ES and IOM have different views on the risk of adverse effects. The IOM recommends 400 IU vitamin D daily for children younger than 1 year, 800 IU for those above 70 years and 600 IU/per day for everyone else. The ES recommend 400-1000 IU daily for all infants and 1500- 2000 IU for adults. Screening, however, is not recommended by either society. To decrease uncertainty concerning the side effects of higher-dose vitamin D treatment, it is important to understand, use and support the function of the pharmacovigilance system of the pharmaceutical industry that manufactures and markets various (prescription, over-the-counter) preparations. This is what the author aims to highlight in the second part of this article. Using this system, both the doctor and the patient can help support and accept the justification of higher-dose vitamin D therapy.]

Lege Artis Medicinae

[Physiological-pathological muscle atrophy in elderly - interventions potencially inhibiting this progressive process ]

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[In old and very old age, one of the most prevalent signs of aged body’s decline is the progressive loss of muscle mass and function. First itself the physiological aging process can be dominant in the complex causative background but later it is usually intertwined with pathological mechanisms. The importance of muscle system is extremely high in the physiological regulation of various vital life processes The paper also points out the far-reaching consequences of sarcopenia syndrome that leads to general weakness, falls, traumas, acceleration of co-morbidities, rapidly declining self independence, ultimately frailty syndrome, and death. The initial body mass index has been recently replaced by a more adequate, more complex diagnostic approachment of sarcopenia that evaluates both muscle mass/strength and physical performance. Prevention or breaking the process of sarcopenia needs complex intervention which includes special fast protein rich diet with leucin and vitamin D combined with frequent physical exercise. ]

Hypertension and nephrology

[The role of vitamin D receptor and the risk reducing effect of vitamin D receptor agonists in chronic kidney disease]

KISS István, KULCSÁR Imre, BARABÁS Noémi, KERKOVITS Lóránt

[Vitamin D3 is produced in the skin and is modified in the liver and kidney to the active metabolite form, 1,25-dyhydroxyvitamin D3 (calcitriol). Calcitriol binds to a nuclear receptor, the vitamin D receptor (VDR), and activates processes that bind to vitamin D. The classical effects of vitamin D receptor activator or agonist (VDRA) therapy for the treatment of secondary hyperparathyroidism in patients with chronic kidney disease primarily involves suppressive effects on the parathyroid gland, and regulation of calcium and phosphorus absorption in the intestine an mobilization in bone. Several VDR agonists have been developed for the treatment of osteoporosis, hyperparathyroidism secondary to chronic kidney disease (CKD), and psoriasis. Secondary hyperparathyroidism (SHPT) is a common and serious consequence of CKD. SHPT is a complex condition characterized by a decline in 1,25-dihidroxi vitamin D and consequent VDR activation, abnormalities in serum calcium and phosphorus levels, parathyroid gland hyperplasia, elevated parathyroid hormone (PTH) secretion, and systemic mineral and bone abnormalities. There are three classes of drug used for treatment of SHPT (non-selective and selective VDR activators, and calcimimetics). Observational studies in hemodialysis patients report improved cardiovascular and allcause survival among those received VDRA therapy compared with those not on VDRA therapy. The survival benefits of selective VDRA paricalcitol appear to be linked to "non classical" action of VDRA, possibly through VDRA-mediated modulation of gene expression. VRDAs are reported to have beneficial effects such as anti-inflammatory and antithrombotic effects, inhibition of vascular calcification and stiffening, inhibition of vascular smooth muscle cell proliferation, and regression of left ventricular hypertrophy. VDRA are also reported to negatively regulate the renin-angiotensin system, which plays a key role in hypertension, myocardial infarction and stroke. Data from epidemiological, preclinical and clinical studies have shown that vitamin D and/or 25(OH) vitamin D deficiency is associated with increased risk for cardiovascular disease (CVD). The selective VDR agonists are associated direct protective effects on glomerular architecture and antiproteinuric effects in response to renal damage. Emerging evidence suggest that VDR plays important roles in modulating cardiovascular, immunological, metabolic and other function. Paricalcitol may prove to have a substantial beneficial effect on cardiac disease and its outcome in patients with CKD.]

LAM KID

[Calcium supplementation and the risk of cardiovascular disease - Real apprehension or picking the spin?]

SPEER Gábor

[Some data shows that calcium supplementation, a basic intervention for treating osteoporosis in postmenopausal women, may increase the risk of atherosclerotic vascular disease. Coronary artery calcified plaque is a marker for atheromatous plaque burden and predicts future risk of cardiovascular events. However, the deposition of calcium into the vascular wall is due to an active mechanism, involving such genes and proteins which play role in bone metabolism. In this work the data about the cardiovascular side effect of calcium supplementation are reviewed. Also, I demonstrate studies with the conclusions that calcium supplements with or without vitamin D do not increase the risk of cardiovascular events, especially that of myocardial infarction.]

LAM KID

[Osteoporotic patient’s use of prescription drugs - pilot study]

BATKA Gábor, SZENTANDRÁSSY Andrea Éva, SZEKERES László

[BACKGROUND - In Hungary, the number of the highest mortality hip fractures is between 12 000-15 000 per year. The cost of treating hip fractures is several times higher than that of preventive medical therapy. Thus, the compliance of patients with osteoporosis is of great importance. METHODS - Using the informatical database of St. András Rheumatology Hospital at Héviz, we collected one year’s prescription drugs for osteoporosis and compared them with the number of drugs obtained by the patients, determined from National Health Insurance data. RESULTS - In general, the patients obtained 75% of prescription drugs. From the 4354 boxes of prescribed antiporotics, 3637 contained bisphosphonate (not considering vitamin D and calcium). Within this group, 88% of combination preparations were obtained, which is a greater ratio than that of non-combination bisphosphonates (84%). CONCLUSIONS - On the basis of our results, we posit that prescription of a combination preparation somewhat improves the patients’ compliance. The low concordance of vitamin D and calcium preparations is worrying.]