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Background In Europe, the rate of 25(OH)D deficiency is considered high. Thus, it seems necessary to conduct population-based studies to fully assess vitamin D deficiency in various groups of patients. Objectives To evaluate serum 25(OH)D levels and the frequency of deficiency in women in Poland with endocrine and osteoporotic disorders. The influences of diet, use of vitamin/mineral supplementation and exposure to ultraviolet (UVB) radiation on vitamin D status in women with metabolic disorders were also examined. Material and methods The patient group consisted of 223 women aged 19-81 years diagnosed with endocrine and/or osteoporotic disorders. The control group consisted of 108 clinically healthy women aged 26-72 years. Serum 25(OH)D concentration was assessed using a chemiluminescent immunoassay (CLIA). An ad hoc questionnaire was used to assess the participants' exposure to UVB radiation. Food intake was assessed using a three-day 24-hour questionnaire interview. Results The following groups showed significantly higher 25(OH)D levels: women taking vitamin D supplements compared to women not taking vitamin D supplements (29.3 ±3.2 compared to 19.5 ±3.7 ng/mL, p = 0.0024); premenopausal women compared to postmenopausal women (28.9 ±5.2 compared to 21.5 ±4.5 ng/mL, p = 0.0021); women who visited sunny countries in the last 6 months compared to women who did not (28.1 ±3.1 ng/mL compared to 24.5 ±5.3 ng/mL, p = 0.0031); and normal weight or overweight women (according to body mass index (BMI)) compared to obese women (27.4 ±4.5 ng/mL compared to 22.3 ±4.7 ng/mL, p = 0.0431). In addition, 25(OH)D concentration correlated with total dietary vitamin D intake in the patient group (R = 0.17, p = 0.0021). Of all examined food groups, fish consumption affected serum 25(OH)D levels in patients (R = 0.20, p = 0.0421) and controls (R = 0.29, p = 0.0002). Consumption of fish products contributed to statistical differences between the patient group (R = 0.17, p = 0.0072) and healthy subjects (R = 0.19, p = 0.0032). Conclusions The most crucial factors influencing vitamin D status in the studied women were regular fish consumption, spending holidays in sunny destinations and regular intake of vitamin D preparations.

Data obtained in recent years clearly demonstrate the aging process of European populations. Consequently, the incidence of osteoporosis has been rising. The aim of this study is to assess the quality of life (QoL) of women with osteoporosis. A total of 260 women participated in this study. The patient group consisted of 170 women with osteoporotic disorders. The control group consisted of 90 healthy women. Participants’ quality of life was measured with the Qualeffo-41 Questionnaire. The total 25(OH)D concentration level was assessed with an assay using the chemiluminescent immunoassay. To assess the pain level, the Visual Analogue Scale (VAS) was used. To assess dietary behaviors, data were obtained by a 13-item Food Frequency Questionnaire. To assess the nutrition knowledge of participants, the Beliefs and Eating Habits Questionnaire was used. Based on the frequency of food intake, participants were classified into three patterns of behavior, i.e., Prudent, Western, and Not Prudent-Not Western. The patients assessed their quality of life as average (36.6 ± 19.9 points). The most favorable scores were obtained in the domains of “Ability to do jobs around the house” and “Mobility”. The worst rated domain among the respondents was “Mental function”. There were significant differences identified in quality of life depending on diet, nutritional knowledge, comorbidities and occurrence of fractures in the subjects. The individuals in the “Prudent” group reported a significantly higher quality of life as compared to the “Not Prudent-Not Western” and “Western” groups and those with high nutritional knowledge as compared to those with moderate and low. Lower quality of life was also observed among women with comorbidities and with bone fractures. Depending on serum 25(OH)D levels, poorer quality of life was characterized women with vitamin D deficiency. Patient education, implementation of effective methods aimed at alleviating pain and maintaining the optimal concentration of vitamin D can help improve the quality of life in patients with osteoporotic disorders.

While low body mass index (BMI) is a risk factor for fractures, the association between obesity and fracture risk is inconsistent and puzzling. Several studies reported higher fracture risk (FR), and others reported lower FR in obese populations. Our narrative review presents the overall incidence of fractures by anatomic locations in adult patients, geriatric populations, and in those after bariatric surgery. In conclusion, obesity should be considered as a fracture risk in adults, as well as falls and fractures in geriatric patients, in particular in those with sarcopenic obesity, and after bariatric surgery. The specific characteristics of fractures risk associated with obesity should be considered by physicians in the diagnostic and therapeutic work-up of obese patients. This review outlines the current literature on this topic and aims to guide physicians regarding proper decisions to prevent fractures in patients with obesity.

There are speculations that vitamin D may be an important regulator of the energy metabolism. The aim of this study was to evaluate the influence of serum 25(OH)D concentration and nutritional status on the resting metabolic rate. The study group consisted of 223 women with endocrine and/or osteoporotic disorders. The control group consisted of 108 women, clinically healthy. The total 25(OH)D concentration level was measured with an assay using chemiluminescent immunoassay technology. Indirect calorimetry was applied to assess the resting metabolic rate. The mean resting metabolic rate was significantly lower in the group of women with metabolic disorders than in the control group. A correlation was found between serum 25(OH)D levels in healthy subjects and the resting metabolic rate. Significantly higher resting metabolic rate was found in women with normal serum 25(OH)D levels in comparison to subjects with deficient vitamin D levels. The control group demonstrated a relationship between body fat tissue and fat-free body mass and the resting metabolic rate. Both 25(OH)D concentration and body composition were factors influencing the resting metabolic rate in the group of healthy subjects. More research is needed to clarify the relationship between vitamin D status and metabolic rate in individuals with endocrine and osteoporotic disorders.

The current increase in the incidence of osteoporosis and osteoporotic fractures among men and the decrease in age in which these first occur raise the question about historical changes in the patterns of bone loss with age, including sex differences, and their biological and cultural determinants in the past. The present study analyzed bone mineral density (BMD) and bone fractures in 267 male skeletons representing six geographically homogeneous populations from the region of Kujawy in north-central Poland, both prehistoric (Middle Neolithic) and historical (early Middle Ages to early modern times). Sex differences in BMD were investigated using data from a previous study of females from these populations (Spinek et al., 2016). In general, the regular patterns of age-related bone loss found in men from the studied archaeological populations were similar to those observed today. In all age groups, Neolithic men showed a significantly higher BMD as compared to the historical samples; on the other hand, the latter revealed similar values to contemporary populations in the middle and old age groups. Thus, in the analyzed period, a major transition in bone maintenance patterns occurred between the Neolithic and the Early Middle Ages. The archaeological populations exhibited a faster rate of bone loss with age: while their initial BMD levels were higher than those in contemporary populations, BMD for the oldest age groups was similar to or even lower than today. The most pronounced sex differences in BMD were found for young adults, which indicates a significantly greater influence of factors limiting peak bone mass and contributing to bone loss in young women, probably associated with reproductive history (age at menarche and pregnancies). The men, and especially young individuals, exhibited a higher prevalence of osteoporotic fractures as compared to the women. The main factor determining such sex- and age-specific patterns of osteoporotic fractures in the analyzed skeletal samples was the generally greater susceptibility to injuries of the males.

The purpose of the study was to assess the expression of selected genes of the Wnt pathway: APC, AXIN1, CTNNB1, DKK1, GSK3β, KREMEN1, SFRP1, WNT1 in peripheral blood mononuclear cells (PBMC) of patients, selected in consideration of their BMD (bone mineral density) and the occurrence of low-energy fractures. The study involved 45 postmenopausal women, divided into 4 groups, according to BMD and fracture history. Measurements of laboratory parameters and RNA expression in PBMC cells were carried out in material, collected once at the inclusion visit. The densitometric examination was performed on all participants. In the analysis of the relative expression levels (REL) of the studied genes in the entire population, we observed an overexpression for SFRP1 in 100% of samples and WNT1. In addition, the REL of DKK1, APC, and GSK3β genes were slightly elevated vs. the calibrator. In contrast, CTNNB1 and AXIN1 presented with a slightly decreased RELs. Analysis did not show any significant differences among the groups in the relative gene expression levels (p

Background: Odanacatib, a cathepsin K inhibitor, reduces bone resorption while maintaining bone formation. Previous work has shown that odanacatib increases bone mineral density in postmenopausal women with low bone mass. We aimed to investigate the efficacy and safety of odanacatib to reduce fracture risk in postmenopausal women with osteoporosis. Methods: The Long-term Odanacatib Fracture Trial (LOFT) was a multicentre, randomised, double-blind, placebo-controlled, event-driven study at 388 outpatient clinics in 40 countries. Eligible participants were women aged at least 65 years who were postmenopausal for 5 years or more, with a femoral neck or total hip bone mineral density T-score between −2·5 and −4·0 if no previous radiographic vertebral fracture, or between −1·5 and −4·0 with a previous vertebral fracture. Women with a previous hip fracture, more than one vertebral fracture, or a T-score of less than −4·0 at the total hip or femoral neck were not eligible unless they were unable or unwilling to use approved osteoporosis treatment. Participants were randomly assigned (1:1) to either oral odanacatib (50 mg once per week) or matching placebo. Randomisation was done using an interactive voice recognition system after stratification for previous radiographic vertebral fracture, and treatment was masked to study participants, investigators and their staff, and sponsor personnel. If the study completed before 5 years of double-blind treatment, consenting participants could enrol in a double-blind extension study (LOFT Extension), continuing their original treatment assignment for up to 5 years from randomisation. Primary endpoints were incidence of vertebral fractures as assessed using radiographs collected at baseline, 6 and 12 months, yearly, and at final study visit in participants for whom evaluable radiograph images were available at baseline and at least one other timepoint, and hip and non-vertebral fractures adjudicated as being a result of osteoporosis as assessed by clinical history and radiograph. Safety was assessed in participants who received at least one dose of study drug. The adjudicated cardiovascular safety endpoints were a composite of cardiovascular death, myocardial infarction, or stroke, and new-onset atrial fibrillation or flutter. Individual cardiovascular endpoints and death were also assessed. LOFT and LOFT Extension are registered with ClinicalTrials.gov (number NCT00529373) and the European Clinical Trials Database (EudraCT number 2007-002693-66). Findings: Between Sept 14, 2007, and Nov 17, 2009, we randomly assigned 16 071 evaluable patients to treatment: 8043 to odanacatib and 8028 to placebo. After a median follow-up of 36·5 months (IQR 34·43–40·15) 4297 women assigned to odanacatib and 3960 assigned to placebo enrolled in LOFT Extension (total median follow-up 47·6 months, IQR 35·45–60·06). In LOFT, cumulative incidence of primary outcomes for odanacatib versus placebo were: radiographic vertebral fractures 3·7% (251/6770) versus 7·8% (542/6910), hazard ratio (HR) 0·46, 95% CI 0·40–0·53; hip fractures 0·8% (65/8043) versus 1·6% (125/8028), 0·53, 0·39–0·71; non-vertebral fractures 5·1% (412/8043) versus 6·7% (541/8028), 0·77, 0·68–0·87; all p

Introduction: Osteoporosis and cardiovascular diseases (CVD) are more common in the elderly population and have similar risk factors. The goal was an evaluation of the correlation between 10-year risk of death from CVD and 10-year bone fracture risk (FRAX). Material and methods: A total of 79 patients of the Regional Centre of Menopause and Osteoporosis of the Military Teaching Hospital in Lodz (Poland), aged 50–83 years, consulted for osteoporosis were divided into two groups: study group — with osteoporosis (O; T-score ≤ –2.5 SD) and control — without osteoporosis (T-sc > –2.5). Bone mineral density was evaluated by densitometric scanning of spine (L2-L4 T-score) and/or femoral neck (Neck T-score) and/or total hip (Total Hip T-score). Total cholesterol (TC), fasting glucose, arterial blood pressure, medical history, and family history were obtained. The risk of fatal-CVD was assessed by Euro Heart Score (EHS), and major osteoporotic (MOFR) and hip fracture risk (HFR) by the FRAX scale. Results: 80% of the patients (32/40) with osteoporosis and 51% (20/39) of the patients without osteoporosis revealed a HeartScore ≥ 5%. There was correlation in the group of all patients between EHS and Neck T-score (p < 0.05; Spearman rank correlation coefficient (Rs) = –0.3806), L2-L4 T-score (p < 0.05; Rs = –0.2891), and Total Hip T-score (p < 0.005; Rs = –0.3561), and in the control group — between EHS and Neck T-score (p < 0.05; Rs = –0.3502). There was a 2.33% difference between the average EHS level to the disadvantage of patients with osteoporosis (p < 0.05). EHS positively correlated with MOFR (p < 0.001) and HFR (p < 0.001) in the whole study popula­tion and with MOFR (p < 0.05) and HFR (p < 0.01) in the group of osteoporotic patients. There were differences between groups in TC (p < 0.001) and BMI (p < 0.001) levels. Conclusions: The 10-year risk of fatal-CVD correlated with osteoporosis and with the 10-year osteoporotic fracture risk. This conclusion may help identify patients who require extended cardiotherapy protocols.

Alterations in the region of the pubic symphysis and of the sacroiliac joints referred to as pelvic scarring are investigated by forensic scientists as potential indicators of pregnancy and parturition. Although pelvic scarring is not exclusively related to obstetrical events, the analysis of the relationship between this trait and skeletal mineral density in archaeological samples can give us a new insight into women's lives. The present study analyzes the relationship between the presence and the degree of pelvic scarring observed on the pelvic bones and bone mineral density (BMD) measured in the proximal femur in 190 skeletons of adult females representing archaeological populations from the region of Kujawy in north-central Poland and dating from 4500 BCE to the early 19th century CE. Multiple regression analysis has shown that 48% of the variability of bone mineral density of the female skeletons is explained by the time periods of the archaeological population, the individual's age at death, the depth of the proximal femur and the pelvic scarring. In all the analyzed skeletal samples, the females with a high degree of pelvic scarring regardless of age at death were characterized by higher bone mineral density than the females without such alterations. A high degree of scarring explains over 3% of the variability of BMD in the analyzed female skeletons. It seems that pelvic scarring together with bone mineral density can shed some light on reproductive phenomena in past populations.

Objectives Paleopathological studies suggest different patterns of age-related bone loss and osteoporosis in past populations compared with those of modern times. However, the observed interpopulational differences are often difficult to interpret due to considerable environmental and biological heterogeneity between populations from which the analyzed skeletal samples come. In the present paper, we try to determine whether there was a directional trend in occurrence of this phenomenon in the past as a consequence of changes in life conditions over the last six thousand years of human history. Materials and methods The study involved 276 female skeletons from four geographically homogeneous populations dated from Neolithic to early modern times coming from a region located in present-day Poland. Bone mineral density and bone fractures were examined for all the skeletons. Polymorphisms of the vitamin D receptor gene associated with low BMD were analyzed using PCR in individuals randomly selected from all of the studied skeletal series. Results In all the analyzed populations, BMD was found to significantly decrease with age. The only statistically significant interpopulational differences were found for the Neolithic skeletal series, with females in all age groups exhibiting higher BMD values and no osteoporotic fractures compared with the historical populations. Discussion The much better bone maintenance in Neolithic women may have resulted from a favorable confluence of high levels of physical activity, exposure to UV radiation, and a diet with an appropriate calcium intake.

Introduction: The aim of this study was to evaluate quantitative changes in OPG and RANKL proteins after treatment with strontium ranelate (SR) and ibandronate in patients with postmenopausal osteoporosis. Material and methods: A total of 89 women with postmenopausal osteoporosis (PO), aged 51-85 years, patients of the Outpatient Clinic of Osteoporosis of the Military Teaching Hospital in Lodz, were enrolled in the study. The patients were randomly assigned to different therapies: ibandronate and (SR). Patients of the control group received only calcium and vitamin D3 supplements. The patients’ visits were repeated after three and six months. Measurements of beta-CTX (C-terminal Telopeptide of type 1 collagen), osteocalcin, RANKL, osteoprotegerin (OPG), alkaline phosphatase concentrations in serum, as well as of total 24-hour calcium and phosphate levels in serum and urine, were carried out in material collected at baseline and after three and six months of therapy. Left hip and lumbar spine densitometry was done twice (at baseline visit and after six months). Results: In all three groups there were no significant differences noted in the concentrations of OPG and RANKL serum protein levels during the study period. Both negative and positive correlations or tendencies of correlations were found between OPG serum concentrations and BMD changes in the SR group. Conclusions: Both ibandronate and SR do not seem to cause any significant changes in OPG and RANKL protein serum levels during the first six months of treatment. OPG may play a role in osteoclast activity suppression in the course of treatment with ibandronate in patients with PO. OPG may play an important role in the mechanism of SR therapy and may be viewed as a potentially valuable parameter for monitoring and predicting the course of treatment with SR in PO. (Endokrynol Pol 2016; 67 (2): 174–184)

The goal of the study was an evaluation of serum vitamin D concentrations in healthy young women.A total of 106 healthy women, aged 20-30 years, were included in the study. Monthly evaluation - for three months - of the effects of calcium (500 mg) and vitamin D (1500 IU) administration in women with baseline values of vitamin D20 ng/mL (Group 1) plus the effects of an 800 IU/d dose in women with the baseline value of D20 ng/mL (Group 2). Additionally, calcium and PTH concentrations were assessed at the study onset and after a three-month supplementation. Only 67 women adhered to the prescribed therapeutic regime during the three months of observation.The mean vitamin D concentration in the entire study group was 16.56 ng/mL, being 12.6 ng/mL in Group 1 and 25.22 ng/mL in Group 2. In the course of vitamin D administration, its concentration increased statistically significantly, both in the entire group and in the subgroups, at all time points compared with the study onset. Moreover, its concentration in the whole population and in Group 1 was significantly higher in each of the time points not only in relation to the baseline, but also in comparison with the results of the previous measurements (after 1 and 2 months of supplementation). In Group 2, vitamin D levels also increased systematically throughout the whole study period, and after 3 months its concentration was significantly higher than after 1 and 2 months. Although there were no differences in calcium concentration after those three months, a statistically significant drop of PTH (p0.05) was recorded in the entire population and in Group 1.A moderate deficiency of vitamin D was observed in the studied population of young women. A supplementation with calcium plus vitamin D brought about an increase of vitamin D concentration as early as in the first month of administration. The optimal concentration of30 ng/mL was achieved in Group 1 after three months of vitamin D administration in 1500 IU/d dose.

It is now assumed that proper functioning of the thyroid gland (TG), beside iodine, requires also a number of elements, including selenium, iron, zinc, copper, and calcium. In many cases, only an adequate supply of one of these microelements (e.g. iodine) may reveal symptoms resulting from deficits of other microelements (e.g. iron or selenium). Selenium is accounted to the trace elements of key importance for homeostasis of the human system, in particular, for the proper functioning of the immune system and the TG. Results of epidemiological studies have demonstrated that selenium deficit may affect as many as one billion people in many countries all over the world. A proper sequence of particular supplementations is also worth emphasising for the significant correlations among the supplemented microelements. For example, it has been demonstrated that an excessive supplementation of selenium may enhance the effects of iodine deficit in endemic regions, while proper supplementation of selenium in studied animals may alleviate the consequences of iodine excess, preventing destructive-inflammatory lesions in the TG. This paper is a summary of the current knowledge on the role of selenium in the functionality of the TG.

Glucocorticoids are quite commonly used in the treatment of many diseases and are one of the most common causes of secondary osteoporosis. Osteoporosis associated with chronic steroid therapy, appears to be an important medical problem. In the USA, glucocorticoids are prescribed to 1 million patients a year. Data from the UK reveal as many as 1.6 million prescriptions for steroid agents within 10 years. Glucocorticoids are used by 0.9% of the total population and approximately 2.5% in the age group of 70–79 years. It is very important to develop the knowledge about osteoporosis, which accompanies chronic steroid therapy, especially with regard to effective counteraction and prevention rules, not only among primary care physicians, but also among patients.

Evaluation of: Rhee CW, Lee J, Oh S, Choi NK, Park BJ. Use of bisphosphonate and risk of atrial fibrillation in elderly women with osteoporosis. Osteoporos. Int. DOI: 10.1007/s00198-011-1608-z (2011) (Epub ahead of print). Osteoporosis is a growing problem in the aging population. It affects postmenopausal women, as well as elderly subjects of both sexes, often with dysfunction of the cardiovascular system or with an increased risk of circulation disorders. It has been found that the mortality rate of subjects with osteoporosis is comparable with that in patients suffering from diseases such as obturative pulmonary disease and myocardial ischemia. Bisphosphonates are the first-line drugs used in the therapy of osteoporosis. However, their administration is associated with a risk of adverse symptoms, which are likely to occur as gastrointestinal tract disturbances, muscular-osseous pains, mandible necrosis and atypical fractures. Recently, an increased risk of atrial fibrillation during bisphosphonate treatment in females has been reported, but the results of some studies are rather controversial. The new paper by Rhee et al., published in Osteoporosis International, presents data from a large cohort study and shows opposite, protective effects of bisphosphonate against atrial fibrillation. It is important for both clinicians and their patients to know whether bisphosphonates increase the risk of cardiac arrhythmia.

article i nfo Purpose: The aim of the cross-sectional study was to establish the degree of conformity between 10-year probability of osteoporotic fracture, assessed by FRAX, and using the nomograms, as proposed by Nguyen at al. Methods: Postmenopausal Polish women (2012) were examined in their mean age of 68.5±7.9 years (age range 55-90 years). Fracture probability by FRAX was based on age, BMI, prior fracture, hip fracture in parents, steroid use, rheumatoid arthritis, alcohol use, secondary osteoporosis and T-score for femoral neck BMD. Fracture probability by Nguyen's nomograms was based on age, the number of prior fractures, the number of falls and T-score for femoral neck BMD. Results:Themean conformity rate was 79.1% forany fracture risk(for threshold 20%) and79.5% for hipfracture (threshold 3%). Any and hip fracture risks were significantly higher for both methods in women with fracture history in comparison to those without fracture and increased with ageing. The influence of prior fracture and ageing was more evident in Nguyen's nomograms. ROC analyses of any fracture risk in FRAX and Nguyen's methods demonstrated the area under curve (AUC) at 0.833 and 0.879, respectively. Similar analyses for hip fracture demonstrated AUCs for FRAX and Nguyen's technique at 0.726 and 0.850, respectively. The AUCs for Nguyen's nomograms were significantly larger than the AUCs for FRAX (pb0.0001). Conclusion:Themean conformity for anyfracture riskis 79.1% and79.5% for hipfracture. Nguyen's nomograms seemtobemoreefficientinfractureriskassessment,especiallyforhipfractures,duetoahigheraccuracyofthe method. The information on the number of falls during the last year and multiple fractures ought to be incorporated into the method of fracture risk prediction. Mini-Abstract: The degree of conformity was assessed in a group of 2012 women between 10-year FRAX prognosis of fracture and Nguyen et al.'s nomograms. The mean conformity for any fracture risk is 79.1% and 79.5%forhipfracture.Nguyen's nomogramsseemtobemoreefficientinfractureriskassessment duetohigher accuracy.

The content of epinephrine (E), norepinephrine (NE) and dopamine (DA) was measured in the adrenals of male Snell dwarf mice, which are characterized by a genetically determined lack of growth hormone (GH), prolactin (PRL) and thyrotropin (TSH), and in normal male mice of the same strain. Additionally, adrenal catecholamine (CA) content of both normal and dwarf mice was determined after 6-day treatment with TSH, GH or PRL. Although the adrenal E content (in saline-, TSH- and PRL-treated groups) and DA content (in saline- and PRL-treated groups) of dwarf mice were significantly lower than those observed in respective groups of normal animals, such differences were not found for NE. The latter finding suggests the presence of a much higher adrenal NE concentration in dwarf mice, since their adrenal glands are several-fold smaller than those of phenotypically normal mice. It is suggested that the increased concentration of NE in dwarfs is related to the reduced activity of an enzyme, phenylethanolamine-N-methyl transferase (PNMT), which converts adrenal NE into E. Moreover, it was demonstrated that GH treatment resulted in abolition of the differences in adrenal E, NE and DA content between normal and dwarf mice. The mechanism of this effect of GH remains unclear.

Introduction: The goal of the study was an evaluation of serum vitamin D concentrations in healthy young women. Material and methods: A total of 106 healthy women, aged 20–30 years, were included in the study. Monthly evaluation — for three months — of the effects of calcium (500 mg) and vitamin D (1500 IU) administration in women with baseline values of vitamin D 20 ng/mL (Group 2). Additionally, calcium and PTH concentrations were assessed at the study onset and after a three-month supplementation. Only 67 women adhered to the prescribed therapeutic regime during the three months of observation. Results: The mean vitamin D concentration in the entire study group was 16.56 ng/mL, being 12.6 ng/mL in Group 1 and 25.22 ng/mL in Group 2. In the course of vitamin D administration, its concentration increased statistically significantly, both in the entire group and in the subgroups, at all time points compared with the study onset. Moreover, its concentration in the whole population and in Group 1 was significantly higher in each of the time points not only in relation to the baseline, but also in comparison with the results of the previous measurements (after 1 and 2 months of supplementation). In Group 2, vitamin D levels also increased systematically throughout the whole study period, and after 3 months its concentration was significantly higher than after 1 and 2 months. Although there were no differences in calcium concentration after those three months, a statistically significant drop of PTH (p < 0.05) was recorded in the entire population and in Group 1. Conclusions: A moderate deficiency of vitamin D was observed in the studied population of young women. A supplementation with calcium plus vitamin D brought about an increase of vitamin D concentration as early as in the first month of administration. The optimal concentration of > 30 ng/mL was achieved in Group 1 after three months of vitamin D administration in 1500 IU/d dose.

Osteoporosis is a serious medical and socioeconomic problem of the 21st century. Mechanical load is a key regulator which controls bone formation and remodelling, with participation of osteocytes. Sclerostin is produced and released by mature osteocytes into bone surface, where it inhibits the conveyance of osteoblast proliferation and differentiation activating signals from mesenchymal cells, thus suppressing new bone formation. The goal of the study was an evaluation of the effects of a 12-week physical training programme on the levels of bone turnover markers [Sclerostin, Osteocalcin (OC), C-terminal telopeptide of type I collagen (β-CTX)] in blood serum of women with osteopenia. Materials & Methods: The study included 50 women of the Regional Menopause and Osteoporosis Centre of the WAM Teaching Hospital, at the age of 50-75 years with the diagnosis of osteopenia, obtained on the basis of hip and/or lumbar spine densitometry (T-score from -1.0 to -2.5 SD). During the initial 12 weeks (between point 1 and 2), the patients maintained their previous, normal level of physical activity. During subsequent 12 weeks (between point 2 and 3), a programme of exercise was implemented. The programme included the interval training on a bicycle ergometer, three times a week for 36 minutes. During the entire study duration, all the patients received a supplementation of calcium (500 mg) and vit. D3 (1800 IU) once daily. Serum levels of OC, alkaline phosphatase (ALP), β-CTX and sclerostin were assayed at 3 time points. Results: After the course of the exercise cycle, the OC concentration was increased, sclerostin levels decreased, while no statistical differences were observed in β-CTX levels vs. the period of physical inactivity. No correlations were found between sclerostin level changes and osteocalcin level changes during the training time, because of too small groups. Neither statistically significant were the differences in alkaline phosphatase, calcium and phosphorus levels. Conclusions: The obtained results emphasise the role of physical training as an effective stimulation method of bone formation processes in women with osteopenia. Sclerostin can be a marker of physical activity.

The aim of this study was to evaluate quantitative changes in OPG and RANKL proteins after treatment with strontium ranelate (SR) and ibandronate in patients with postmenopausal osteoporosis.A total of 89 women with postmenopausal osteoporosis (PO), aged 51-85 years, patients of the Outpatient Clinic of Osteoporosis of the Military Teaching Hospital in Lodz, were enrolled in the study. The patients were randomly assigned to different therapies: ibandronate and (SR). Patients of the control group received only calcium and vitamin D3 supplements. The patients' visits were repeated after three and six months. Measurements of beta-CTX (C-terminal Telopeptide of type 1 collagen), osteocalcin, RANKL, osteoprotegerin (OPG), alkaline phosphatase concentrations in serum, as well as of total 24-hour calcium and phosphate levels in serum and urine, were carried out in material collected at baseline and after three and six months of therapy. Left hip and lumbar spine densitometry was done twice (at baseline visit and after six months).In all three groups there were no significant differences noted in the concentrations of OPG and RANKL serum protein levels during the study period. Both negative and positive correlations or tendencies of correlations were found between OPG serum concentrations and BMD changes in the SR group.Both ibandronate and SR do not seem to cause any significant changes in OPG and RANKL protein serum levels during the first six months of treatment. OPG may play a role in osteoclast activity suppression in the course of treatment with ibandronate in patients with PO. OPG may play an important role in the mechanism of SR therapy and may be viewed as a potentially valuable parameter for monitoring and predicting the course of treatment with SR in PO.

STAT3 (signal transducer and activator of transcription 3) is an important cellular effector in the Jak/STAT signaling pathway, which plays a pivotal role in human immune system regulation, mediating the effect of different cytokines. In the present study, we assessed the correlation between STAT3 polymorphisms (rs3816769 C>T and rs744166 A>G) and risk of the autoimmune thyroid diseases (AITDs) Hashimoto’s thyroiditis (HT) and Graves’ disease (GD) in the Polish population. Moreover, we evaluated the association of polymorphisms with the thyroid autoantibody levels (TPOAb, TgAb, TRAb) and the correlation between circulating proinflammatory IL6 and IL17 cytokines and thyroid autoantibody levels. The study included 71 AITD patients with HT (n = 39) or GD (n = 32) and a control group (n = 40). DNA SNP genotyping was performed using TaqMan probes. Serum levels of thyroid autoantibodies, IL6 and IL17 were measured according to enhanced chemiluminescence (ECL) assay. Allele A of STAT3 SNP rs744166 A>G was significantly more frequent in both HT and GD patients, while allele G was significantly more frequent in the control group. Similarly, allele C and CC genotype of STAT3 SNP rs3816769 C>T were significantly more frequent in the control group in comparison to HT and GD patients. Significantly higher TgAb median values were associated with CT rs3816769 genotype in HT patients. Serum levels of IL6 and IL17 positively correlated with TPOAb in the HT group. Serum level of IL6 positively correlated with TPOAb in the AITD group. Both studied polymorphisms seem to play a significant role in susceptibility to AITD (HT and GD). STAT3 SNPs may influence TAb level in AITD patients.

The aim of the study was the presentation of osteoporotic fracture prediction in men.Eight-hundred and one men at the mean age of 70.8 ± 9.31 years were examined. The 10-year fracture prediction was established, using the FRAX calculator and Garvan nomogram.The mean value for any fracture and hip fracture probabilities for FRAX were 7.26 ± 5.4% and 3.68 ± 4.25%, respectively. For Garvan fracture, risk values were 26.44 ± 23.83% and 12.02 ± 18.1%. The mean conformity for any fracture and hip fracture prediction for threshold of 20% (any fracture) and 3% (hip fracture) between Garvan and FRAX values was 55.8% (κ 0.041) and 79.65% (κ 0.599), respectively. ROC analyses showed the following areas under the ROC curves (AUC) for any fractures: FRAX 0.808 and Garvan nomogram 0.843 (p = 0.059). The AUC values for hip fractures were 0.748 for Garvan nomogram and for 0.749 FRAX, and did not differ. On the base of ROC data, the cut-off values with best accuracy to predict fractures for both methods were established. The conformity between methods for thresholds indicated by ROC analysis was 72.5% (κ 0.435) for any and 77.7% (κ 0.543) for hip fractures.The conformities between FRAX and Garvan in regard to hip fracture prediction were acceptable for a threshold of 3% and thresholds derived by ROC analysis, while for any fracture we recommend to use thresholds established by ROC analysis. This may suggest that the use of "universal" cut-off points is probably misleading.

The protection afforded by melatonin against paraquat-induced genotoxicity in both bone marrow and peripheral blood cells of mice was tested using micronuclei as an index of induced chromosomal damage. Melatonin (2 mg/kg) or an equal volume of saline was injected i.p. into mice 30 min prior to the i.p. administration of paraquat (two injections of 15 mg/kg; the paraquat injections were given with a 24 h interval) and thereafter at 6 h intervals to the conclusion of the study (72 h). Using fluorescence microscopy, the number of micronuclei in polychromatic erythrocytes (MN-PCE) per 2000 PCE (1000 PCE/slide) per mouse was counted both in blood and bone marrow, and the ratio of PCE to normochromatic erythrocytes (NCE) (PCE/NCE) was calculated. Paraquat treatment increased the number of MN-PCE at 24, 48, and 72 h, both in peripheral blood and bone marrow cells, while no differences were observed in the PCE/NCE ratio. Melatonin inhibited the paraquat-induced increase in MN-PCE by more than 50% at 48 and 72h. Paraquat toxicity is believed to be due to free radical generation. Since melatonin is known to be an efficient free radical scavenger, it is concluded that melatonin's protection against paraquat-induced genotoxicity is mediated, at least in part, by its free radical scavenging activity.

Melatonin protection against ethanol-induced gastroduodenal injury was investigated in duodenum-ligated rats. Melatonin, injected i.p. 30 min before administration of 1 ml of absolute ethanol, given by gavage, significantly decreased ethanol-induced macroscopic, histological and biochemical changes in the gastroduodenal mucosa. Ethanol-induced lesions were detectable as haemorrhagic streaks. Ethanol administration damaged 36% and 25% of the total gastric and duodenal surface, respectively. Melatonin treatment reduced ethanol-induced gastric and duodenal damage to 14% and 8%, respectively. When indomethacin was given together with ethanol, the gastric damaged area was 44% of the total surface, while the duodenal damaged area was 35%; melatonin administration reduced the damage to only 13% of the total gastric surface and to 12% of total duodenal surface. Both stomach and duodenum of ethanol-treated animals showed polymorphonuclear leukocyte (PMN) infiltration. The number of PMN increased more than 600 and 200 times in stomach and duodenum, respectively, following ethanol administration. Melatonin treatment reduced ethanol-induced PMN infiltration by 38% in the stomach and 20% in the duodenum. In indomethacin-ethanol-treated rats, the number of PMN increased by 875% compared to control group in the stomach and by 264% in duodenum. Melatonin administration reduced the indomethacin-ethanol-induced PMN rise by 57% in the stomach and 40% in the duodenum. Gastroduodenal total glutathione (tGSH) concentration and glutathione reductase (GSSG-Rd) activity were significantly reduced following ethanol and indomethacin-ethanol administration. Melatonin ameliorated both the decrease in tGSH concentration as well as the reduction of GSSG-Rd activity elicited by ethanol both in the stomach and duodenum; melatonin was effective against indomethacin-ethanol-induced damage only in the stomach. Ethanol-induced gastroduodenal damage is believed to be mediated by the generation of free radicals. Recently, a number of in vivo and in vitro experiments have shown melatonin to be an effective antioxidant and free radical scavenger; thus, we conclude that the protection by melatonin against ethanol-induced gastroduodenal injury is due, at least in part, to its radical scavenging activity. British Journal of Pharmacology (1997) 121, 264–270; doi:10.1038/sj.bjp.0701104

Autoimmune thyroid diseases (AITDs), including Hashimoto' s thyroiditis (HT) and Graves' disease (GD), are related to environmental and genetic factors. We analyzed the association of cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) gene two polymorphisms (+49 A/G, -318 C/T) with HT and GD development in Polish children, and correlated both polymorphisms with the production of thyroid autoantibodies (TPOAb and TgAb). The study involved 49 AITD patients (age 10-19) with HT (n=25) or GD (n=24) and 69 healthy controls. SNP genotyping was performed using genomic DNA and TaqMan® probes. The obtained results indicated that CTLA-4 +49 GG genotype was significantly more frequent in both HT and GD patients, whereas the AA genotype was more common in controls. CTLA-4-318 CT genotype was significantly more frequent in AITD, and the CC genotype more often occurred in controls. Significantly higher median TPOAb and TgAb values were associated with G allele in HT, and with T allele in GD patients. Concluding, both studied polymorphisms seem to be important genetic determinants of the risk of HT and GD, and appear to be associated with a predisposition to high levels of TAbs and clinical AITD. The obtained results give more information on the distribution of the CTLA-4 polymorphism in Polish AITD children, and further support the proposal that the CTLA-4 gene plays an important role in a TAb production.

By the impact of demographic changes and as the result of the 'incorrect' lifestyles pursued in developed societies, osteoporosis has become a serious social problem. Hip fracture is the most serious complication of osteoporosis and is associated with high mortality rates or permanent health impairment. The goal of this study was an evaluation of the impact of selected socio-economic factors and of the time period from fracture to surgical intervention on the patient's prognosis.A group of 148 patients (114 women and 34 men) participated in the study, their age varying between 48 and 93 years, all of them after surgical treatment of hip fracture. A questionnaire study was carried out, encompassing all the participants.During a year-long follow up, thirty-four (34) patients, i.e. 23% of the whole group, passed away. Further comparisons were performed between two groups: Group A - 114 patients, who survived the follow up period, and Group B - those who died. The mean age of patients was 76.3 and 82.6 years in Groups A and B, respectively (p 〈 0.05). In Group A, 79.8% of the patients declared full self-dependence prior to fracture episode vs. 44.1% of the patients in Group B (p 〈 0.05). Regular physical activity - in various forms - was undertaken by 39.5% of the patients in Group A and 11.8% of those in Group B (p 〈 0.05). Active ways of spending outdoor time were reported by 32.5% of the patients in Group A vs. 14.7% in Group B (p 〈 0.05). Fracture unfavourably influenced the material situation of affected patients. No relationship was found between the time period from fracture to surgery and the patient's prognosis.1. Despite the currently available surgical treatment methods, hip fracture is still laden with a high risk of fatality. 2. High physical activity, especially outdoors, self-dependence and having a partner positively influence patient's prognosis after hip fracture. 3. Hip fracture negatively changes the material situation of patients. 4. The length of time from hip fracture to operation has no effect on the survival rate.

Recent research results have confirmed the high significance of the OPG/RANK/RANKL system in the development of bone diseases.The aim of the reported study was to assess gene expression levels of the OPG/RANK/RANKL system in peripheral blood mononuclear cells (PBMCs) after strontium ranelate (SR) and ibandronate administered to patients with postmenopausal osteoporosis.A total of 89 postmenopausal women, aged 51 to 85 years, patients of the Outpatient Clinic of Osteoporosis of the Military Teaching Hospital in Lodz, were enrolled into the study. The patients were randomly assigned to different medical therapies: ibandronate and SR. Patients of the control group received only calcium and vitamin D₃ supplements. Patient visits were repeated after 3 and 6 months. Measurements of serum alkaline phosphatase concentrations and of RNA expression in PBMCs as well as of total serum calcium and phosphate levels and of their 24-hour urine excretion rates were carried out in material, collected at baseline and after 3 and 6 months of the therapy. Densitometry of the left hip and of the lumbar spine was done at the baseline visit and after 6 months.The differences in gene expressions of RANKL and RANK were not significant during the study period and did not differ between the groups in a statistically significant manner. No OPG gene expression was observed in PBMCs of patients in any of the studied groups and at any time point. The tendency of correlation (P = .07) was observed between decreasing RANK gene expression and increasing bone mineral density in the patients treated with SR.Both ibandronate and SR do not seem to cause any significant changes in gene expression levels of OPG/RANK/RANKL in PBMCs during the first 6 months of treatment.

Three experiments employing male and female Syrian hamsters (aged 1, 2, and 8-10 months), male Sprague-Dawley rats (aged 1, 2, and 10 months) and male C57B1 mice (aged 2, 7, 13, and 29 months) examined the effects of age and sex on Mg(2+)-dependent and Ca2+, Mg(2+)-dependent ATPase activity in the Harderian gland. Significant differences due to age and sex were observed in the hamsters and rats but not with age in mice. Generally, male hamsters had significantly higher Mg(2+)-dependent and Ca2+, Mg(2+)-dependent (exception at one timepoint) ATPase activity than did females. Age-matched male and female rats had similar values of Mg(2+)-dependent ATPase activity, but males had significantly higher Ca2+, Mg(2+)-dependent ATPase activity than females at 2 months of age.

The ability of melatonin to protect against paraquat-induced oxidative damage in rat lung, liver, and serum was examined. Changes in the levels of malondialdehyde (MDA) plus 4-hydroxyalkenals (4-HDA) and reduced and oxidized glutathione concentrations were measured. Paraquat (50 mg/kg) was injected i.p. into either Sprague-Dawley or Wistar rats with or without the co-administration of 5 mg/kg melatonin. Paraquat alone increased MDA + 4-HDA levels in serum and lungs of both rat strains, with these increases being abolished by melatonin co-treatment. Paraquat also decreased reduced glutathione levels and increased oxidized glutathione concentrations in lung and liver; these changes were negated by melatonin. The effect of melatonin on paraquat-induced mortality was also studied. Paraquat at a dose of 79 mg/kg was lethal for 50% of animals within 24 hr; when administered together with melatonin, the LD50 for paraquat increased to 251 mg/ kg.

The aim of the study was to examine the impact of social competence of physicians on the effectiveness of patient compliance and persistence with therapy.The study included physicians and their patients, previously diagnosed with osteoporosis, and eligible to receive pharmacological treatment. The physicians were evaluated with the social competence questionnaire involving three dimensions: social exposure, intimacy and assertiveness, as well as in the combined scale. All patients in the study group were prescribed the same medication: alendronate once a week. Compliance and persistence of the patients were juxtaposed with social interaction skills of physicians during 7 scheduled appointments at 2-month intervals.Doctor's effectiveness in situations demanding close interpersonal contact was higher in the group with good compliance--group A (p0.001), as well as in the situations of social exposure, (p0.001). On the other hand, their assertiveness was higher in the group with poor compliance--group B (p0.001). Co-morbid conditions (group A: 76%, group B: 74%), as well as earlier fractures (40.43% vs. 36.78%) were comparable in both groups. Disease acceptance and suggested methods of treatment were more often accepted by patients from group A than group B (56% vs. 33%, respectively).(1) Disease acceptance is essential for effective treatment. (2) Social skills of physicians influence patient adherence to therapy recommendations. (3) Close interpersonal contact between physicians and their patients eliminates the feeling of fear and

INTRODUCTION The aim of the study was to assess the role of patient counselling, nurse assistance and effects of biochemical examinations in adherence of women with postmenopausal osteoporosis to alendronate 70 administration over 12 months of therapy. MATERIAL AND METHODS Compliance and persistence to alendronate 70 therapy were assessed in a prospective study of 123 postmenopausal women, followed up for one year. The patients were divided into 4 groups (controls, counselled group, biochemical group and nurse assisted group) with monitoring every 6 months; in the nurse assisted group, additional phone contacts were made after 3 and 9 months of treatment. After 12 months, compliance and persistence were analysed. The medication possession ratio (MPR) was regarded as optimal when its value exceeded 80%. RESULTS The compliance to alendronate 70 therapy was 54.03% in the control group and the mean persistence with medication was 197 days. The MPR above 80% was observed in 37.5%, and, after 1 year, 43.75% of patients were found persistent with the therapy. In the remaining groups, both compliance and persistence were higher but not statistically significantly, compared to the control group. Neither patient's age, education, diet, nor physical activity influenced the compliance with prescribed therapy. The most common reason to discontinue therapy was either its side effects or smoking. CONCLUSIONS The obtained results suggest that better adherence with medical recommendations is observed in patients who receive additional attention, e.g. counselling, biochemical tests or nursing care. The critical elements for therapy discontinuation were side effects and smoking.

Vitamin D is necessary in maintaining appropriate calcium and phosphate homeostasis in the body (classical function) and ensuring appropriate functioning of many tissues, organs and cells, unrelated to mineral economy (non-classical function). Vitamin D deficiency in adults may cause osteomalacia, increase fracture risk in osteoporosis, induce cardiovascular diseases, diabetes type 1 and 2, multiple sclerosis, Lesniowski-Crohn disease, and cancer, including colon, breast, and prostate cancer. Possible causes of vitamin D deficiency in a healthy population include decreased cutaneous synthesis and an inadequate intake of vitamin D, both in food and in supplements. Vitamin D deficiency level (25(OH) D.20 ng/mL), is fairly widespread, being found in a substantial percentage of healthy subjects around the world, regardless of race, gender and age. Daily vitamin D dose, as determined by the Food and Nutrition Board in 1997, is now rather insufficient, the biggest problem being associated with maximal vitamin D levels (50 μg/day) in actually available food supplements. Nowadays, it is recommended that adults need a minimum of 800-1,000 U/day when their exposure to the sun is inadequate (in Poland from October to April). This dosage should be provided to all subjects who avoid sunlight, as well as to those aged over 65 because of their slower skin synthesis of vitamin D and for its proven anti-fracture and anti-fall effects.

Steroid-induced osteoporosis is a textbook example of the secondary type of this medical condition. Glucocorticosteroids suppress bone formation by their direct and indirect effect on osteoblasts, osteoclasts and osteocytes, increasing their resorption and, eventually, leading to negative bone balance. A clinical problem arises regarding the fact that approximately 50% of patients on chronic steroid therapy undergo asymptomatic bone fractures. The treatment mode includes minimising the dose of administered steroids, encouraging an improved lifestyle and supplementation with adequate calcium and vitamin D(3) doses. Bisphosphonates are a group of medical agents used both to prevent and treat steroid-induced osteoporosis, although new therapies have also become available in recent years.

Bacterial lipopolysaccharide (LPS) causes lipid peroxidation (LPO). We have found that LPS induces LPO in tissue homogenates in vitro in a concentration-dependent manner, the concentration of 400 μg/ml demonstrating the most efficient lipid damaging effect. Antioxidant properties of melatonin are unquestionable and have been proved both in vivo and in vitro. It has been demonstrated that also melatonin metabolites and derivatives inhibit oxidative stress. The aim of our study was to compare the effects of melatonin (MEL) and indole compound: 6-methoxytryptophol, on LPS-induced LPO in vitro. Malondialdehyde (MDA) plus 4-hydroxyalkenal (4-HDA) concentrations were measured as the indicators of induced membrane peroxidative damage in brain, liver and kidney homogenates. Both melatonin and 6-methoxytryptophol were used at increasing concentrations, starting from 0.01-5 mM, together with LPS at one concentration of 400 μg/ml. In all the examined tissues, LPS stimulated LPO, while both melatonin and 6-methoxytryptophol released LPS-stimulated LPO. Furthermore, the capacity of 6-methoxytryptophol reducing LPO was higher than that of melatonin. The results of the reported study clearly indicate that 6-methoxytryptophol is a much stronger antioxidant in vitro than melatonin in terms of reducing oxidative damage to lipid membranes. However, it remains still unclear how the features relate to in vivo circumstances.

More than half of those with chronic diseases, including osteoporosis, discontinue treatment during the first year of its administration. This problem increases over the course of continued follow-up. Additionally, it has been observed that 13% of women, prescribed oral daily alendronate, do not even start the treatment, while 20% of patients discontinue the therapy during the first four months. On the other hand, those patients who are compliant achieve increased bone mass density with a simultaneous decrease of fracture risk. The aim of our study was to assess the adherence to the recommended alendronate 70 administration protocol over the course of 12 months by women with post-menopausal osteoporosis.Adherence (compliance plus persistence) to alendronate 70 therapy was assessed in a prospective study of 153 post-menopausal women, followed up for one year with monitoring every two months.Adherence to therapy of all the study participants was high during the entire study period, the patients remaining compliant after a year in 95.08 ± 1.39% (mean ± SEM) of cases, and the mean persistence with medication was 347.05 ± 5.07 days. In the group of patients who interrupted treatment, the mean persistence was 212.44 days. One of the study participants did not start the treatment, and another two discontinued the therapy within 30-60 days of the study onset (between the first two visits). Facilitated contacts with the doctor, continuous access to prescribed treatment and frequent visits significantly improved patient compliance. The common reason for discontinuation was side effects, while age (but not education) affected the rate of compliance with therapy. The worst results were obtained in the group of patients with osteoporosis diagnosed more than five years before the study, particularly in the subgroup where alendronate was being used for the first time or where treatment resumed after a substantial break.The obtained results indicate that better adherence to alendronate 70 therapy, administered once a week, depends on more frequent monitoring of treated patients.

Osteoporosis is a chronic disease of the osseous system characterised by decreased strength of bone tissue, which in turn leads to increased fracture risk. It has been demonstrated that osteoporosis affects more than 30% of women after the menopause (World Health Organization, 1994). However, the disease is also observed in men. The primary goals of osteoporosis therapy include prevention of low-energy fractures and general improvement of quality of life. Any patient with diagnosed osteoporosis requires, besides prevention, the application of proper treatment. Of the available therapeutic options, the best are bisphosphonates, medical agents with well identified properties, therapeutic efficacy, and safety which has been confirmed in many clinical studies. Therefore, they are recommended as first line drugs for osteoporosis. The efficacy of oral preparations may be limited, due to low bioavailability, complications and adverse effects from the gastrointestinal tract. So the parenteral administration of bisphosphonates is a valuable alternative. A fine example of such therapy is the intravenous administration of ibandronate. Short injection time periods and the relatively long, three-month intervals between administrations are unquestionable advantages of this therapy mode. In addition, the therapy does not constrain a patient's everyday activity, and simultaneously provides regular contact with doctors and the therapeutic centre. Additionally, a good tolerance of the drug and its high therapeutic efficacy, proven by appreciably reduced fracture risks, significantly improves the quality of life of patients suffering from osteoporosis. This paper is a thorough review of current knowledge on the efficacy and safety of i.v. ibandronate in osteoporosis therapy, as presented in the latest literature reports.

Introduction Autoimmune thyroid disease (AITD) is associated with both genetic and environmental factors which lead to the overactivity of immune system. Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4) gene polymorphisms belong to the main genetic factors determining the susceptibility to AITD (Hashimoto's thyroiditis, HT and Graves' disease, GD) development. The aim of the study was to evaluate the relationship between CTLA-4 polymorphisms (A49G, 1822 C/T and CT60 A/G) and HT and/or GD in Polish patients. Material and methods Molecular analysis involved AITD group, consisting of HT (n=28) and GD (n=14) patients, and a control group of healthy persons (n=20). Genomic DNA was isolated from peripheral blood and CTLA-4 polymorphisms were assessed by polymerase chain reaction-restriction fragment length polymorphism method, using three restriction enzymes: Fnu4HI (A49G), BsmAI (1822 C/T) and BsaAI (CT60 A/G). Results Statistical analysis (χ(2) test) confirmed significant differences between the studied groups concerning CTLA-4 A49G genotypes. CTLA-4 A/G genotype was significantly more frequent in AITD group and OR analysis suggested that it might increase the susceptibility to HT. In GD patients, OR analysis revealed statistically significant relationship with the presence of G allele. In controls, CTLA-4 A/A genotype frequency was significantly increased suggesting a protective effect. There were no statistically significant differences regarding frequencies of other genotypes and polymorphic alleles of the CTLA-4 gene (1822 C/T and CT60 A/G) between the studied groups. Conclusions CTLA-4 A49G polymorphism seems to be an important genetic determinant of the risk of HT and GD in Polish patients.

In earlier studies from other laboratories it was shown that melatonin decreased ovarian weight in rats and inhibited compensatory hypertrophy of the remaining ovary after unilateral ovariectomy. This study was designed to examine the influence of melatonin on certain indices of ovarian hyperplasia and/or hypertrophy in adult female rats with both ovaries preserved and with either an intact pineal gland or with the pineal gland removed (pinealectomy, PX) or, finally, in sham-PX animals. Similar studies were conducted on rats after unilateral ovariectomy, referring the examined parameters to the remaining intact ovary. The studies included mitotic activity of granulosa layer cells and corpus luteum cells, ovarian weight, ovarian cross-sectional area, cross-sectional area of the granulosa layer of all the Graafian follicles and the cross-sectional areas of the corpora lutea, visible on the ovarian cross-section. On the basis of results, we conclude that: 1) the effect of PX on the processes of ovarian hyperplasia and hypertrophy may vary; analogously, exogenous melatonin administration may influence ovarian hyperplasia and hypertrophy in different ways; 2) PX and exogenous melatonin may, under certain conditions, exert similar biological effects, even synergistic effects; 3) melatonin inhibits ovarian growth processes, while the effects of PX are variable; 4) the results indicate that in experiments performed on rats, with the use of two control groups, i.e., intact and sham-PX, melatonin effects on these two groups may differ.

Vitamin D is necessary in maintaining appropriate calcium and phosphate homeostasis in the body (classical function) and ensuring appropriate functioning of many tissues, organs and cells, unrelated to mineral economy (non-classical function). Vitamin D deficiency in adults may cause osteomalacia, increase fracture risk in osteoporosis, induce cardiovascular diseases, diabetes type 1 and 2, multiple sclerosis, Lesniowski-Crohn disease, and cancer, including colon, breast, and prostate cancer. Possible causes of vitamin D deficiency in a healthy population include decreased cutaneous synthesis and an inadequate intake of vitamin D, both in food and in supplements. Vitamin D deficiency level (25(OH) D. 〈 20 ng/mL), is fairly widespread, being found in a substantial percentage of healthy subjects around the world, regardless of race, gender and age. Daily vitamin D dose, as determined by the Food and Nutrition Board in 1997, is now rather insufficient, the biggest problem being associated with maximal vitamin D levels (50 μg/day) in actually available food supplements. Nowadays, it is recommended that adults need a minimum of 800-1,000 U/day when their exposure to the sun is inadequate (in Poland from October to April). This dosage should be provided to all subjects who avoid sunlight, as well as to those aged over 65 because of their slower skin synthesis of vitamin D and for its proven anti-fracture and anti-fall effects.

Bacterial lipopolysaccharide (LPS) causes lipid peroxidation (LPO). We have found that LPS induces LPO in vitro, in tissue homogenates in a concentration-dependent manner, the concentration of 400 µg/ml demonstrating the most efficient lipid damaging effect . Both melatonin and its precursor, N-acetylserotonin, must possess antioxidant activities, both in vivo or in vitro, however, following some claims, N-acetylserotonin is a more effective extra- and intracellular antioxidant than melatonin. The aim of our study was to compare the effects of melatonin and N-acetylserotonin on the LPS-induced LPO in vitro.Malondialdehyde (MDA) plus 4-hydroxyalkenal (4-HDA) concentrations were measured as the indices of induced membrane peroxidative damage in brain, liver and kidney homogenates. Both melatonin and N-acetylserotonin were used at increasing concentrations, starting from 0.01-5 mM, together with LPS at one concentration level of 400 µg/ml.In all the examined tissues, LPS stimulated LPO, while both melatonin and N-acetylserotonin decreased LPS-stimulated LPO. Furthermore, the capacity of N-acetylserotonin reducing LPO was higher than that of melatonin.The results of the reported study clearly indicate that N-acetylserotonin is a much stronger antioxidant in vitro than melatonin in terms of reducing oxidative damage to lipid membranes. However, it remains still unclear how the features relate to in vivo circumstances.

A possible role of antioxidants in thyreotoxicosis was investigated. We examined the parameters of lipid peroxidation (LPO): conjugated dienes (CD), malondialdehyde (MDA), Schiff bases (SB) in lung homogenates of male Wistar rats.Two control groups were created: Group 1 - intact animals and Group 2 - animals injected with 0,9% NaCl. In Experiment I, the animals received L-thyroxin (LT4) i.p. (Groups 3-7). After one week the rats received additionally: Group 4 - melatonin (MEL); Group 5 - propylthiouracil (PTU); Group 6 - Ambroxol (AMB); Group 7 - N-acetylocysteine (NAC). In Experiment II, the animals received only antioxidants.In Experiment I, we noticed a significantly higher MDA and SB level in Group 2, compared to that in Group 1. Moreover, we observed a significantly higher MDA and SB level in Group 3, vs. that in Group 1, but SB level was lower in Group 3 than in Group 2. Melatonin, PTU and NAC reduced CD; PTU, AMB diminished MDA and MEL, AMB lowered SB levels as compared to Group 3. In Experiment II, we observed significantly higher MDA and SB level in Group 2, vs. that in Group 1. Melatonin, AMB and NAC decreased MDA and SB level, when compared to Group 2 but PTU elevated MDA and SB level vs. that in Group 1.1) L-T4 suppresses LPO, 2) MEL, AMB and NAC protect against LPO, 3) PTU is an antioxidant in thyreotoxicosis, however, when administered alone, it enhances LPO, 4) stress accelerate LPO.